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Displaying One Session
- Floriana Morgillo (Napoli, Italy)
- Oliver Gautschi (Luzern, Switzerland)
Open & welcome
- Oliver Gautschi (Luzern, Switzerland)
LBA85 - REACTION: A phase II study of etoposide and cis/carboplatin with or without pembrolizumab in untreated extensive small cell lung cancer
- Benjamin Besse (Villejuif, CEDEX, France)
Abstract
Background
Anti-PD-L1 antibodies extend overall survival (OS) of patients with extensive disease Small Cell Lung Cancer (ED-SCLC) when combined with platinum-etoposide (Pl-E) from cycle 1. We evaluated the benefit of first-line pembrolizumab (P) combined with Pl-E from cycle 3 in the subgroup of chemo-sensitive ED-SCLC.
Methods
REACTION is a multicenter, open-label, randomized phase II trial. Patients with ED-SCLC, unselected for PD-L1, with PS 0/1 and controlled brain metastases who achieved an objective response after 2 X Pl-E were randomized 1:1 to experimental arm (EXP) P in combination with 4 X Pl-E then P up to 35 cycles vs. 4 X Pl-E in the control (CTRL) arm. Cross-over to P-Pl-E was allowed for CTRL. Primary endpoint was progression free survival (PFS) from randomization. With a 1-sided alpha 10%, the study was powered at 90% level to detect a Hazard Ratio (HR) of 0.575 in PFS.
Results
Between Feb 7, 2018 and Oct 31, 2019, 125 patients were recruited (61 in EXP arm vs 64 in CTRL arm) with 119 (58 vs 61) eligible and receiving at least one dose of treatment (Per Protocol [PP] population). Median age was 65 vs 63.5 years with the majority being male (72 vs 56%), PS 1 (62 vs 60%), and rare brain metastases (8 vs 11%). Most patients had partial response (PR) to the induction chemo (98% in each arm). 19 patients crossed over to P-E-Pl. Among 124 patients who started treatment, grade ≥3 adverse events were observed in 43 vs 36%, while only 2 patients (1 in each arm) had grade 5 toxicity. Among PP patients, 107 PD or deaths were observed. The response rate was 61% (67 vs 56%). Median follow-up time with respect to OS was 14.2 months in EXP and 14.0 months in CTRL arm. Median PFS (80% CI) was 4.7 months (4.5, 5.3) vs 5.4 (4.9, 5.5), HR = 0.84 (0.65, 1.09) and 1-sided p=0.194. Median OS (80% CI) was 12.3 months (10.2, 14.5) vs 10.4 (8.5, 11.6), HR = 0.73 (0.54, 1.0) and 1-sided p=0.097.
Conclusions
P combined with Pl-E was well tolerated but did not improve PFS over Pl-E in chemo-sensitive patients with ED-SCLC. The OS however showed P combined with Pl-E significantly improved OS at 1-sided 10% level.
Clinical trial identification
NCT02580994.
Legal entity responsible for the study
EORTC.
Funding
MSD.
Disclosure
B. Besse: Research grant/Funding (institution): AbbVie; Research grant/Funding (institution): Amgen; Research grant/Funding (institution): AstraZeneca; Research grant/Funding (institution): BeiGene; Research grant/Funding (institution): Blueprint Medicines; Research grant/Funding (institution): BMS; Research grant/Funding (institution): Boehringer Ingelheim; Research grant/Funding (institution): Celgene; Research grant/Funding (institution): Cristal Therapeutics; Research grant/Funding (institution): Daiichi-Sankyo; Research grant/Funding (institution): Eli Lilly; Research grant/Funding (institution): GSK; Research grant/Funding (institution): Ignyta; Research grant/Funding (institution): Ipsen; Research grant/Funding (institution): Inivata; Research grant/Funding (institution): Janssen; Research grant/Funding (institution): Merck KGaA; Research grant/Funding (institution): MSD; Research grant/Funding (institution): Nektar; Research grant/Funding (institution): Onxeo; Research grant/Funding (institution): OSEI immunotherapeutics; Research grant/Funding (institution): Pfizer; Research grant/Funding (institution): PharmaMar; Research grant/Funding (institution): Roche-Genentech; Research grant/Funding (institution): Sanofi; Research grant/Funding (institution): Servier; Research grant/Funding (institution): Spectrum Pharmaceuticals; Research grant/Funding (institution): Takeda; Research grant/Funding (institution): Tiziana Pharma; Research grant/Funding (institution): Tolero Pharmace. J. Menis: Travel/Accommodation/Expenses: Bristol-Myers Squibb; Travel/Accommodation/Expenses: AstraZeneca; Advisory/Consultancy, Travel/Accommodation/Expenses: msd; Advisory/Consultancy: Roche; Advisory/Consultancy, Travel/Accommodation/Expenses: Boehringer Ingelheim. L. Greillier: Honoraria (self): AbbVie; Honoraria (self): Novartis; Honoraria (self): MSD; Honoraria (self): AstraZeneca; Honoraria (self): roche; Honoraria (self): BMS; Honoraria (self): Boehringer Ingelheim; Honoraria (self): Pfizer; Honoraria (self): Takeda. C. Decroisette: Advisory/Consultancy: Roche; Advisory/Consultancy: BMS; Advisory/Consultancy: MSD; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Pfizer. R. Califano: Honoraria (self), Research grant/Funding (institution): Bristol-Myers Squibb; Honoraria (self), Research grant/Funding (institution): AstraZeneca; Honoraria (self), Research grant/Funding (institution): Pfizer; Honoraria (self), Research grant/Funding (institution): Roche; Honoraria (self): Boehringer Ingelheim; Research grant/Funding (institution): AbbVie; Honoraria (self), Research grant/Funding (institution): MSD; Honoraria (self): Bayer; Honoraria (self), Research grant/Funding (institution): Takeda; Honoraria (self), Research grant/Funding (institution): Novartis; Honoraria (self), Research grant/Funding (institution): Eli Lilly; Research grant/Funding (institution): Clovis; Shareholder/Stockholder/Stock options: The Christie Private Care. A-M.C. Dingemans: Non-remunerated activity/ies: AbbVie; Research grant/Funding (institution): Amgen; Honoraria (self): Pfizer; Honoraria (self): Roche; Honoraria (self): Boehringer Ingelheim; Research grant/Funding (institution): BMS; Honoraria (self): Takeda; Honoraria (self): Novartis; Honoraria (self): Eli Lilly; Honoraria (self): Pharma Mar. All other authors have declared no conflicts of interest.
LBA86 - Durvalumab (D) ± tremelimumab (T) + platinum-etoposide (EP) in 1L ES-SCLC: Characterization of long-term clinical benefit and tumour mutational burden (TMB) in CASPIAN
- Jonathan W. Goldman (Santa Monica, CA, United States of America)
Abstract
Background
In the phase III CASPIAN trial, 1L D+EP significantly improved OS vs EP (HR 0.73 [95% CI 0.59‒0.91; p=0.0047]) in pts with ES-SCLC, with sustained benefit after >2 yr median follow-up (HR 0.75 [95% CI 0.62‒0.91; nominal p=0.0032]). Landmark analyses indicated 22% of pts were alive at 24m with the addition of D±T to EP. Here we assess the clinical characteristics and outcomes of pts deriving long-term benefit, as well as the relationship between TMB and efficacy outcomes in the ITT population.
Methods
805 pts with ES-SCLC were randomised 1:1:1 to D+EP, D+T+EP, or EP. Exploratory subgroup analyses defined long-term clinical benefit as PFS ≥12m. Tumour tissue was mandated at screening, if available. TMB was assessed in tissue (tTMB) using the FoundationOne CDx platform.
Results
45 (17%), 42 (16%), and 12 (5%) pts treated with D+EP, D+T+EP, and EP had PFS ≥12m, respectively (data cutoff 27 Jan 2020). In all arms, the PFS ≥12m subgroup had a higher incidence of favorable prognostic factors (more women and pts with PS 0, fewer pts with brain/liver metastases). In the D+EP arm, pts with PFS ≥12m received more D (median 25 vs 7 cycles) and had improved ORR (96% vs 63%), median DoR (NR vs 4m) and OS at 24m (77% vs 11%) compared with the PFS <12m subgroup (Table). Similar results were observed with EP and when both IO arms were combined. Safety and additional efficacy outcomes in the subgroups will be presented. Across all 3 arms, 283 pts (35% of ITT) were evaluable for tTMB. tTMB was not predictive of a differential treatment effect for D±T+EP vs EP (OS, PFS, or ORR).
D+EP IO arms combined PFS ≥12m n=45 PFS <12m n=220 PFS ≥12m n=87 PFS <12m n=444 Ongoing durvalumab at DCO, n (%) 27 (60) 5 (2) 50 (57) 12 (3) Durvalumab cycles, median (range) 25 (6–37) 7 (1–28) 25 (2–37) 6 (1–33) Male, % 60 73 63 75 Never / ever smoker, % 9 / 91 8 / 92 9 / 91 7 / 93 PS 0 / 1, % 47 / 53 35 / 65 48 / 52 36 / 64 Brain mets, % 7 11 3 14 Liver mets, % 20 44 23 46 ORR, n/N (%) 43 / 45 (96) 139 / 220 (63) 82 / 87 (94) 256 /443 (58) Median DoR, m (95% CI) NR (18–NE) 4 (3.5–5) NR (24–NE) 4 (4–5) OS at 24m, % (95% CI) 77(61–87) 11 (7–16) 82 (72–89) 11 (8–14)
Conclusions
Across all arms, pts with PFS ≥12m had exceptional 2 yr OS rates >75%, despite some having poor prognostic factors such as baseline brain or liver metastases. There were >3 times more pts deriving long-term benefit when treated with durvalumab + EP vs EP alone. Further investigation into predictive factors for long-term benefit with durvalumab is ongoing.
Clinical trial identification
NCT03043872; release date: February 6, 2017.
Editorial acknowledgement
Medical writing provided by Beena John, PhD, of Cirrus Communications (Macclesfield, UK), an Ashfield company, and was funded by AstraZeneca.
Legal entity responsible for the study
AstraZeneca PLC.
Funding
AstraZeneca.
Disclosure
J.W. Goldman: Advisory/Consultancy, Research grant/Funding (institution): Genentech; Advisory/Consultancy, Research grant/Funding (self): AstraZeneca. M.C. Garassino: Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution), Non-remunerated activity/ies: Eli Lilly; Advisory/Consultancy: Boehringer Ingelheim; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Otsuka Pharmaceutical; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): AstraZeneca; Advisory/Consultancy, Research grant/Funding (institution): Novartis; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Bristol-Myers Squibb; Advisory/Consultancy, Research grant/Funding (institution): Roche; Advisory/Consultancy, Research grant/Funding (institution), Non-remunerated activity/ies: Pfizer; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Celgene; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Incyte; Advisory/Consultancy: Inivata; Advisory/Consultancy, Speaker Bureau/Expert testimony: Takeda; Research grant/Funding (institution): Tiziana Life Sciences; Research grant/Funding (institution): Clovis; Research grant/Funding (institution): Merck Serono; Advisory/Consultancy, Research grant/Funding (institution): Bayer; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution), Non-remunerated activity/ies: MSD; Advisory/Consultancy, Research grant/Funding (institution): GlaxoSmithKline; Advisory/Consultancy: Sanofi; Advisory/Consultancy, Research grant/Funding (institution): Spectrum Pharmaceuticals; Advisory/Consultancy, Research grant/Funding (institution): Blueprint Medicines; Advisory/Consultancy: Seattle Genetics; Advisory/Consultancy: Daiichi Sankyo; Research grant/Funding (institution): United Therapeutics Corporation; Research grant/Funding (institution): Merck KGaA; Advisory/Consultancy: Janssen; Non-remunerated activity/ies: Turning Point; Research grant/Funding (institution): Ipsen; Research grant/Funding (institution): Exelixis. Y. Chen: Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): AstraZeneca; Advisory/Consultancy, Speaker Bureau/Expert testimony: Genentech; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Bristol-Myers Squibb; Speaker Bureau/Expert testimony: Merck; Advisory/Consultancy, Speaker Bureau/Expert testimony: Novartis; Advisory/Consultancy, Speaker Bureau/Expert testimony: Takeda; Speaker Bureau/Expert testimony: Eli-Lilly; Speaker Bureau/Expert testimony: Guardant Health; Advisory/Consultancy: Pfizer; Advisory/Consultancy: Array Biopharma; Research grant/Funding (institution): Ipsen; Research grant/Funding (institution): Roche. N. Reinmuth: Honoraria (self), Non-remunerated activity/ies: AstraZeneca; Honoraria (self), Non-remunerated activity/ies: Boehringer Ingelheim; Non-remunerated activity/ies: AbbVie; Honoraria (self), Non-remunerated activity/ies: Hoffman la-Roche; Honoraria (self): MSD Sherp & Dohme Gmbh; Honoraria (self): Takeda; Honoraria (self), Non-remunerated activity/ies: Bristol-Myers Squibb; Honoraria (self), Non-remunerated activity/ies: Pfizer. K. Hotta: Honoraria (self): Pfizer; Honoraria (self), Research grant/Funding (institution): Eli-Lilly; Honoraria (self), Research grant/Funding (institution): AstraZeneca; Honoraria (self), Research grant/Funding (institution): Bristol-Myers Squibb; Honoraria (self): Ono; Honoraria (self), Research grant/Funding (institution): MSD; Honoraria (self), Research grant/Funding (institution): Chugai; Honoraria (self): Nippon Kayaku; Honoraria (self): Taiho; Honoraria (self): Boehringer Ingelheim; Honoraria (self): Novartis; Honoraria (self): Daiichi Sankyo; Honoraria (self): Kyorin; Research grant/Funding (institution): Astellas. M. Özgüroğlu: Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Janssen; Honoraria (self), Advisory/Consultancy: Sanofi; Honoraria (self), Honoraria (institution), Advisory/Consultancy, Speaker Bureau/Expert testimony: Astellas; Honoraria (self): Novartis; Honoraria (self): Roche; Travel/Accommodation/Expenses: Bristol-Myers Squibb. S. Spencer: Full/Part-time employment: AstraZeneca. M. Xie: Full/Part-time employment: AstraZeneca. S. Jones: Full/Part-time employment: AstraZeneca. A. Franks: Shareholder/Stockholder/Stock options, Full/Part-time employment: AstraZeneca. Y. Shrestha: Full/Part-time employment: AstraZeneca. L. Paz-Ares: Leadership role, Myself: Genomica, Altum Sequencing; Travel/Accommodation/Expenses: Roche, AstraZeneca, AstraZeneca Spain, Merck Sharp and Dohme, Bristol-Myers Squibb, Lilly, Pfizer; Honoraria (self): Roche/Genentech, Lilly, Pfizer, Boehringer Ingelheim, Bristol-Myers Squibb, Merck Sharp and Dohme; Honoraria (self): AstraZeneca, Merck Serono, PharmaMar, Novartis, Celgene, Sysmex, Bayer, Amgen, Blueprint, Incyte; Spouse/Financial dependant, Fees [immediate family member]: Novartis, Ipsen, Pfizer, Servier, Sanofi, Roche, Amgen, Merck. All other authors have declared no conflicts of interest.
1781MO - IMpower133: Characterisation of long-term survivors treated first-line with chemotherapy ± atezolizumab in extensive-stage small cell lung cancer
- Stephen V. Liu (Washington, D.C., DC, United States of America)
Abstract
Background
In IMpower133, adding atezolizumab (atezo; anti–PD-L1) to carboplatin (C) + etoposide (E) for the first-line treatment (tx) of extensive-stage small cell lung cancer (ES-SCLC) led to improvements in OS and PFS vs placebo (PBO) + CE. OS benefit persists with longer follow-up. Here, we report exploratory analyses of long-term survivors (LTS) in IMpower133.
Methods
Eligible patients (pts) with tx-naive ES-SCLC received four 21-day cycles of C (AUC 5 mg • mL/min IV, day 1) + E (100 mg/m2 IV, days 1-3) with either atezo (1200 mg IV, day 1) or PBO, followed by maintenance tx with atezo or PBO until unacceptable toxicity, disease progression or loss of clinical benefit. Co-primary endpoints were investigator-assessed PFS and OS. This exploratory analysis included characterisation of LTS, defined as pts who survived ≥ 18 mo post randomisation; pts who died < 18 mo post randomisation were defined as non-LTS. Pts who were censored at < 18 mo were excluded. Association of LTS with pt and disease characteristics was explored.
Results
At data cutoff (24 Jan 2019), median follow-up in the ITT population was 22.9 mo; 373 pts were included in this exploratory analysis. There were more LTS in the atezo + CE arm (n = 61, 33.5%; 95% CI: 26.7, 40.9) than in the PBO + CE arm (n = 39, 20.4%; 95% CI: 14.9, 26.8). Among LTS, baseline categories with a > 5% difference between tx arms included age, sex, ECOG PS, LDH and brain metastases (Table). Median SLD was lower in the LTS vs the non-LTS group. Biomarker status (bTMB; PD-L1) did not appear to be associated with long-term survival benefit.
Baseline characteristics LTS (n = 100) Non-LTS (n = 273) Atezo + CE (n = 61) PBO + CE (n = 39) Atezo + CE (n = 121) PBO + CE (n = 152) < 65 y 31 (50.8) 26 (66.7) 69 (57.0) 74 (48.7) ≥ 65 y 30 (49.2) 13 (33.3) 52 (43.0) 78 (51.3) Male 35 (57.4) 25 (64.1) 81 (66.9) 98 (64.5) Female 26 (42.6) 14 (35.9) 40 (33.1) 54 (35.5) 0 32 (52.5) 18 (46.2) 35 (28.9) 46 (30.3) 1 29 (47.5) 21 (53.8) 86 (71.1) 106 (69.7) 91 (12-239) 89 (27-208) 122 (12-325) 112 (15-353) n 60 39 117 148 ≤ ULN 37 (61.7) 20 (51.3) 38 (32.5) 61 (41.2) > ULN 23 (38.3) 19 (48.7) 79 (67.5) 87 (58.8) 4 (6.6) 2 (5.1) 13 (10.7) 14 (9.2)
Conclusions
In IMpower133, more pts in the atezo + CE arm than in the PBO + CE arm were LTS. While sample size was small, exploratory analyses suggest that pts with ES-SCLC can derive benefit from the addition of atezo to chemotherapy regardless of the pt and disease characteristics evaluated, confirming atezo + CE as standard of care for pts with untreated ES-SCLC.
Clinical trial identification
NCT02763579.
Editorial acknowledgement
Medical writing assistance for this abstract was provided by Kia C. E. Walcott, PhD, of Health Interactions.
Legal entity responsible for the study
F. Hoffmann-La Roche, Ltd.
Funding
F. Hoffmann-La Roche, Ltd.
Disclosure
S.V. Liu: Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: AstraZeneca, Merck/MSD; Advisory/Consultancy, Travel/Accommodation/Expenses: Genentech/Roche; Advisory/Consultancy: Boehringer Ingelheim, Janssen, Loxo, PharmaMar, Takeda; Advisory/Consultancy, Research grant/Funding (institution): BMS; Advisory/Consultancy: Celgene, G1 Therapeutics, Guardant Health, Inviata; Advisory/Consultancy, Research grant/Funding (institution): Eli Lilly; Advisory/Consultancy, Research grant/Funding (institution): Pfizer; Advisory/Consultancy: Regeneron; Research grant/Funding (institution): Alkermes; Research grant/Funding (institution): Bayer; Research grant/Funding (institution): Blueprint; Research grant/Funding (institution): Corvus; Research grant/Funding (institution): Debiopharm; Research grant/Funding (institution): Lycera; Research grant/Funding (institution): Molecular Partners; Research grant/Funding (institution): Rain Therapeutics; Research grant/Funding (institution): RAPT; Research grant/Funding (institution): Spectrum; Research grant/Funding (institution): Turning Point Therapeutics. L. Horn: Advisory/Consultancy: Amgen; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Genentech/Roche; Advisory/Consultancy: Merck; Advisory/Consultancy: Incyte; Advisory/Consultancy: EMD Serono; Advisory/Consultancy: Bayer; Advisory/Consultancy, Research grant/Funding (institution): Xcovery; Research grant/Funding (institution): BMS; Research grant/Funding (institution): Boehringer Ingelheim; Advisory/Consultancy: Pfizer. T. Mok: Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution), Shareholder/Stockholder/Stock options: AstraZeneca; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Eli Lilly; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Roche/Genentech, BMS, Boehringer Ingelheim, Novartis, MSD, Pfizer; Honoraria (self), Advisory/Consultancy: Merck Serono, Oncogenex, Ignyta Inc, Celgene, Janssen, OrigiMed, Hengrui Therapeutics, Sanofi-Aventis R&D, Yuhan Corporation, Vertex; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Clovis Oncology; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): SFJ Pharmaceuticals; Honoraria (self), Advisory/Consultancy: ACEA Biosciences; Advisory/Consultancy: geneDecode; Honoraria (self), Speaker Bureau/Expert testimony, Research grant/Funding (institution): Taiho; Research grant/Funding (institution): Eisai; Honoraria (self), Advisory/Consultancy: Fishawack Facilitate Ltd; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Takeda; Honoraria (self), Advisory/Consultancy, Shareholder/Stockholder/Stock options: HutchisonChiMed; Honoraria (self), Research grant/Funding (institution): XCovery; Shareholder/Stockholder/Stock options: Sanomics; Shareholder/Stockholder/Stock options: Loxo Oncology; Honoraria (self), Speaker Bureau/Expert testimony: Amoy Diagnostics. A. Mansfield: Honoraria (institution): AbbVie; Honoraria (institution): AstraZeneca; Honoraria (institution): BMS; Honoraria (institution): Genentech/Roche; Travel/Accommodation/Expenses: Roche; Research grant/Funding (institution): Novartis; Research grant/Funding (institution): Verily; Non-remunerated activity/ies: Mesothelioma Applied Research Foundation. R. De Boer: Honoraria (self), Advisory/Consultancy: Roche Australia; Research grant/Funding (institution): Roche. S. Sugawara: Honoraria (self): Chugai Pharma; Honoraria (self): AstraZeneca; Honoraria (self): MSD; Honoraria (self): BMS; Honoraria (self): Ono Pharmaceutical; Honoraria (self): Nippon Boehringer Ingelheim; Honoraria (self): Eli Lilly & Co.; Honoraria (self): Pfizer; Honoraria (self): Novartis; Honoraria (self): Taiho Pharmaceutical; Honoraria (self): Kyowa Hakko Kirin. R. Dziadziuszko: Honoraria (self): Roche; Honoraria (self): AstraZeneca; Honoraria (self): Takeda; Honoraria (self): Pfizer; Honoraria (self): SeattleGenetics; Honoraria (self): Novartis; Honoraria (self): FoundationMedicine; Honoraria (self): Merck & Co.; Honoraria (self): Merck; Honoraria (institution): CelonPharma . A. Smolin: Advisory/Consultancy: Roche; Advisory/Consultancy: MSD; Advisory/Consultancy: BMS; Advisory/Consultancy: Boehringer Ingelheim; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Eli Lilly; Advisory/Consultancy: Takeda; Advisory/Consultancy: BIOCAD; Advisory/Consultancy: Merck KGaA; Advisory/Consultancy: GSK. M.J. Hochmair: Advisory/Consultancy: Boehringer Ingelheim; Advisory/Consultancy: Roche; Advisory/Consultancy: BMS; Advisory/Consultancy: MSD; Advisory/Consultancy: Takeda. M.C. Garassino: Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): BMS; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Roche; Research grant/Funding (institution): Tiziana Sciences, Merck, Clovis; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: AstraZeneca; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Celgene; Honoraria (self), Research grant/Funding (institution): Otsuka Pharma; Advisory/Consultancy, Research grant/Funding (institution): Bayer; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Pfizer; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): MSD; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Eli Lilly; Advisory/Consultancy, Research grant/Funding (institution): Novartis; Research grant/Funding (institution): Merck KGaA; Research grant/Funding (institution): AstraZeneca AB; Research grant/Funding (institution): United Therapeutics Corporation; Honoraria (self), Research grant/Funding (institution): Incyte Corporation; Advisory/Consultancy, Research grant/Funding (institution): Spectrum Pharmaceuticals; Research grant/Funding (institution): Exelixis Inc., GSK S.p.A; Advisory/Consultancy: Boehringer Ingelheim, Seattle Genetics, Daiichi Sankyo, Inviata, Sanofi Aventis, Janssen, GSK; Advisory/Consultancy: Blueprint Medicine; Honoraria (self), Advisory/Consultancy: Takeda; Honoraria (self): MedImmune; Leadership role: Women for Oncology Italy; Leadership role: ESMO Task Forces. S. Lam: Full/Part-time employment: Genentech. M. McCleland: Full/Part-time employment: Genentech; Shareholder/Stockholder/Stock options: Roche Holdings. A. Cardona: Full/Part-time employment: Roche. S. Morris: Shareholder/Stockholder/Stock options, Full/Part-time employment: Roche. M. Reck: Honoraria (self), Advisory/Consultancy: AbbVie; Honoraria (self), Advisory/Consultancy: Amgen; Honoraria (self), Advisory/Consultancy: AstraZeneca; Honoraria (self), Advisory/Consultancy: BMS; Honoraria (self), Advisory/Consultancy: Boehringer Ingelheim; Honoraria (self), Advisory/Consultancy: Lilly; Honoraria (self), Advisory/Consultancy: Merck; Honoraria (self), Advisory/Consultancy: MSD; Honoraria (self), Advisory/Consultancy: Novartis; Honoraria (self), Advisory/Consultancy: Pfizer; Honoraria (self), Advisory/Consultancy: Roche; Honoraria (self), Advisory/Consultancy: Samsung. All other authors have declared no conflicts of interest.
1782MO - Health-related quality of life (HRQoL) in KEYNOTE-604: Pembrolizumab (pembro) or placebo added to etoposide and platinum (EP) as first-line therapy for ES-SCLC
- Hye Ryun Kim (Seoul, Korea, Republic of)
Abstract
Background
In the randomized, double-blind, phase 3 KEYNOTE-604 study (NCT03066778), pembro-EP significantly improved PFS and had no unexpected toxicities vs placebo-EP as first-line therapy for ES-SCLC; the HR for OS favored pembro-EP, but the significance threshold was missed. We present patient-reported outcomes (PROs) from KEYNOTE-604.
Methods
453 patients (pts) were randomized 1:1 to pembro 200 mg Q3W or saline placebo for ≤35 cycles plus 4 cycles of standard-dose EP. PRO questionnaires, including the EORTC QLQ-C30 and QLQ-LC13, were administered electronically before other trial-related procedures at cycles 1-9, 11, 13, 15, and 17, treatment discontinuation, and the 30-day safety follow-up. Mean change from baseline to wk 18 in the QLQ-C30 global health status (GHS)/QoL scale and time to true deterioration (TTD) in the QLQ-C30/LC13 composite of cough, chest pain, or dyspnea were secondary study end points; TTD in the QLQ-C30 GHS/QoL scale was a protocol-specified exploratory end point. TTD was defined as time to first ≥10-point worsening from baseline with confirmation under a right-censoring rule. HRQoL was assessed in all treated pts who completed ≥1 PRO assessment (N = 439).
Results
PRO compliance was ≥89% in both arms at baseline and wk 18. Mean QLQ-C30 GHS/QoL scale score was 60.54 in the pembro-EP arm and 58.37 in the placebo-EP arm at baseline. Score improved in both arms at wk 18; the least squares mean change from baseline (95% CI) was 8.66 points (5.26-12.06) in the pembro-EP arm and 4.23 points (0.93-7.52) in the placebo-EP arm for a difference in least squares means of 4.43 points (95% CI 0.21-8.66;
Conclusions
Adding pembro to EP did not decrease, and may improve, HRQoL compared with placebo-EP as first-line therapy for ES-SCLC. Along with the efficacy and safety data observed in KEYNOTE-604, PRO data support the benefit of pembro in SCLC.
Clinical trial identification
NCT03066778, originally posted on February 28, 2017.
Editorial acknowledgement
Melanie Leiby of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.
Legal entity responsible for the study
Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.
Funding
Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.
Disclosure
H.R. Kim: Honoraria (self), Speaker Bureau/Expert testimony: Ono; Honoraria (self), Speaker Bureau/Expert testimony: Roche; Speaker Bureau/Expert testimony, Research grant/Funding (institution): MSD. M.M. Awad: Advisory/Consultancy: AbbVie; Advisory/Consultancy: Achilles Therapeutics; Advisory/Consultancy: ARIAD; Advisory/Consultancy: AstraZeneca/MedImmune; Advisory/Consultancy: Blueprint Medicines; Advisory/Consultancy: Boehringer Ingelheim; Advisory/Consultancy, Research grant/Funding (self), Research grant/Funding (institution): Bristol-Myers Squibb; Advisory/Consultancy: Clovis Oncology; Advisory/Consultancy: Foundation Medicine; Advisory/Consultancy, Research grant/Funding (institution): Genentech; Advisory/Consultancy: Gristone Oncology; Advisory/Consultancy: Hengrui Therapeutics; Advisory/Consultancy: Maverick Therapeutics; Advisory/Consultancy, Research grant/Funding (institution): Merck Sharp & Dohme Corp.; Advisory/Consultancy: Nektar; Advisory/Consultancy: Neon Therapeutics; Advisory/Consultancy: Novartis; Advisory/Consultancy: Pfizer; Advisory/Consultancy: Syndax; Research grant/Funding (institution): AstraZeneca; Research grant/Funding (institution): Lilly. A. Navarro: Advisory/Consultancy, Travel/Accommodation/Expenses: Boehringer Ingelheim; Advisory/Consultancy: Bristol-Myers Squibb; Advisory/Consultancy, Travel/Accommodation/Expenses: Pfizer; Advisory/Consultancy: Roche; Speaker Bureau/Expert testimony: Oryzon Genomics; Research grant/Funding (institution): MSD. M. Gottfried: Honoraria (self), Advisory/Consultancy: Roche; Honoraria (self), Advisory/Consultancy: Novartis; Honoraria (self), Advisory/Consultancy: Bristol-Myers Squibb; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): MSD; Honoraria (self), Advisory/Consultancy: AstraZeneca. S. Peters: Honoraria (institution), Advisory/Consultancy: AbbVie; Honoraria (institution), Advisory/Consultancy, Research grant/Funding (institution): Amgen; Honoraria (institution), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: AstraZeneca; Honoraria (institution), Advisory/Consultancy: Bayer; Honoraria (institution), Advisory/Consultancy: Biocartis; Honoraria (institution), Advisory/Consultancy: Bioinvent; Honoraria (institution), Advisory/Consultancy: Blueprint Medicines; Honoraria (institution), Advisory/Consultancy, Research grant/Funding (institution): Boehringer Ingelheim; Honoraria (institution), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Bristol-Myers Squibb; Honoraria (institution), Advisory/Consultancy, Research grant/Funding (institution): Clovis; Honoraria (institution), Advisory/Consultancy, Travel/Accommodation/Expenses: Daiichi Sankyo; Honoraria (institution), Advisory/Consultancy: Debiopharm; Honoraria (institution), Advisory/Consultancy: Eli Lilly; Honoraria (institution), Advisory/Consultancy, Research grant/Funding (institution): F. Hoffmann-La Roche; Honoraria (institution), Advisory/Consultancy: Foundation Medicine; Honoraria (institution), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Illumina; Honoraria (institution), Advisory/Consultancy: Janssen; Honoraria (institution), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: MSD; Honoraria (institution), Advisory/Consultancy, Research grant/Funding (institution): Merck Serono; Honoraria (institution), Advisory/Consultancy: Merrimack; Honoraria (institution), Advisory/Consultancy, Research grant/Funding (institution): Novartis; Honoraria (institution), Advisory/Consultancy: Pharma Mar; Honoraria (institution), Advisory/Consultancy, Research grant/Funding (institution): Pfizer; Honoraria (institution), Advisory/Consultancy: Regeneron; Honoraria (institution), Advisory/Consultancy: Sanofi; Honoraria (institution), Advisory/Consultancy, Travel/Accommodation/Expenses: Seattle Genetics; Honoraria (institution), Advisory/Consultancy: Takeda; Honoraria (institution), Advisory/Consultancy: Vaccibody; Travel/Accommodation/Expenses: Roche; Research grant/Funding (institution): Biodesix. T. Csőszi: Advisory/Consultancy: Novartis pharma SAS; Travel/Accommodation/Expenses: Roche; Research grant/Funding (institution): MSD. P.K. Cheema: Honoraria (self), Advisory/Consultancy: AstraZeneca; Honoraria (self), Advisory/Consultancy: Hoffman la Roche; Honoraria (self), Advisory/Consultancy: MSD; Honoraria (self), Advisory/Consultancy: Novartis; Honoraria (self), Advisory/Consultancy: Pfizer; Honoraria (self), Advisory/Consultancy: Takeda; Advisory/Consultancy: Amgen; Advisory/Consultancy: Bristol-Myers Squibb; Advisory/Consultancy: EMD Serono; Advisory/Consultancy: Genomic Health. D. Rodriguez-Abreu: Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Bristol-Myers Squibb; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution), Travel/Accommodation/Expenses: MSD; Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Roche. M. Wollner: Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): MSD; Honoraria (self), Advisory/Consultancy: AstraZeneca; Honoraria (institution), Speaker Bureau/Expert testimony: Roche; Advisory/Consultancy: Takeda; Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Bristol-Myers Squibb; Advisory/Consultancy, Travel/Accommodation/Expenses: Pfizer; Speaker Bureau/Expert testimony: Boehringer Ingelheim; Speaker Bureau/Expert testimony: Novartis. J.C-H. Yang: Honoraria (institution), Advisory/Consultancy: Boehringer Ingelheim; Honoraria (institution), Advisory/Consultancy: Novartis; Honoraria (institution), Advisory/Consultancy: AstraZeneca; Honoraria (institution), Advisory/Consultancy: Roche/Genentech; Honoraria (institution), Advisory/Consultancy: Eli Lilly; Honoraria (institution), Advisory/Consultancy, Research grant/Funding (institution): MSD; Honoraria (institution), Advisory/Consultancy: Merck Serono; Honoraria (institution), Advisory/Consultancy: Celgene; Honoraria (institution), Advisory/Consultancy: Bayer; Honoraria (institution), Advisory/Consultancy: Pfizer; Honoraria (institution), Advisory/Consultancy: Ono Pharmaceutical; Honoraria (institution), Advisory/Consultancy: Bristol-Myers Squibb; Honoraria (institution), Advisory/Consultancy: Yuhan; Honoraria (institution), Advisory/Consultancy: Hansoh; Honoraria (institution), Advisory/Consultancy: Blueprint Medicines; Honoraria (institution), Advisory/Consultancy: Daiichi Sankyo; Honoraria (institution), Advisory/Consultancy: Amgen; Honoraria (institution), Advisory/Consultancy: Takeda; Honoraria (institution), Advisory/Consultancy: Incyte; Advisory/Consultancy: Roche. J. Mazieres: Advisory/Consultancy, Research grant/Funding (institution): AstraZeneca; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Bristol-Myers Squibb; Advisory/Consultancy: Lilly/ImClone; Advisory/Consultancy, Research grant/Funding (institution): MSD; Advisory/Consultancy: Novartis; Advisory/Consultancy, Travel/Accommodation/Expenses: Pfizer; Advisory/Consultancy: Pierre Fabre; Advisory/Consultancy: Roche/Genentech; Research grant/Funding (institution), Travel/Accommodation/Expenses: Roche. F.J. Orlandi: Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): Roche/Genentech; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy, Research grant/Funding (self): Bristol-Myers Squibb; Advisory/Consultancy: Lilly; Advisory/Consultancy, Research grant/Funding (institution): MSD Oncology; Advisory/Consultancy: Novartis; Advisory/Consultancy, Research grant/Funding (self): Pfizer; Advisory/Consultancy, Research grant/Funding (self): Sanofi; Speaker Bureau/Expert testimony: AstraZeneca/Genentech; Research grant/Funding (self): AstraZeneca/MedImmune; Speaker Bureau/Expert testimony: Roche; Research grant/Funding (self): Amgen; Research grant/Funding (self): Astellas Medivation; Research grant/Funding (self): Boehringer Ingelheim; Research grant/Funding (self): Celltrion; Research grant/Funding (self): mAbxience; Research grant/Funding (self): Nektar. A. Luft: Research grant/Funding (institution): MSD. M. Gümüş: Honoraria (institution), Advisory/Consultancy, Travel/Accommodation/Expenses: Roche; Honoraria (institution): Novartis; Honoraria (institution): Bristol-Myers Squibb; Honoraria (institution), Research grant/Funding (institution): MSD; Honoraria (institution): Amgen; Honoraria (institution), Travel/Accommodation/Expenses: Pfizer; Advisory/Consultancy: Gen İlac; Advisory/Consultancy: Astellas. T. Kato: Research grant/Funding (institution): MSD. G.P. Kalemkerian: Research grant/Funding (institution): Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc. Y. Luo, M.L. Santorelli, M.C. Pietanza: Shareholder/Stockholder/Stock options, Full/Part-time employment: Merck Sharp & Dohme Corp. C.M. Rudin: Advisory/Consultancy: AbbVie; Advisory/Consultancy: Amgen; Advisory/Consultancy: Ascentage Pharma; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Celgene; Advisory/Consultancy, Research grant/Funding (institution): Daiichi Sankyo; Advisory/Consultancy: Genentech/Roche; Advisory/Consultancy: Harpoon Therapeutics; Advisory/Consultancy: Loxo; Advisory/Consultancy: PharmaMar; Research grant/Funding (institution): Pfizer; Research grant/Funding (institution): Viralytics; Research grant/Funding (institution): Merck Sharp & Dohme Corp.; Advisory/Consultancy: Bicycle Therapeutics; Advisory/Consultancy: Bridge Medicines; Advisory/Consultancy: Ipsen; Research grant/Funding (institution): AbbVie/Stemcentrx.
Invited Discussant LBA85, LBA86, 1781MO and 1782MO
- Floriana Morgillo (Napoli, Italy)
1895MO - Three-year follow-up results of the MERIT trial: A Japanese phase II study of nivolumab in malignant pleural mesothelioma
- Hidetoshi Hayashi (Osaka, Japan)
Abstract
Background
Malignant pleural mesothelioma (MPM) is a rare and highly aggressive malignancy with poor prognosis.In Japan, nivolumab was approved in August 2018 for patients with pemetrexed-platinum doublet-treated MPM based on the MERIT trial results.Here, we report the 3-year follow-up data of the MERIT trial to update the previous report.
Methods
Enrollment criteria were as follows: Japanese patients with advanced or metastatic MPM previously treated with up to two chemotherapy regimens, with histologically confirmed measurable lesions and an ECOG performance status (PS) of 0-1. There was no restriction on the programmed death-ligand 1 (PD-L1) status. Patients received nivolumab 240 mg/body every 2 weeks until disease progression or unacceptable toxicity was indicated. The primary endpoint was objective response rate (ORR) (mRECIST assessment by an independent review committee), and the secondary endpoints were disease control rate (DCR), duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety.
Results
Thirty-four patients were enrolled in this study: 85.3% men; median age: 68.0 (43–78) years; PS 1: 61.8%; epithelioid/sarcomatoid/biphasic: 79.4%/8.8%/11.8%; 1 prior regimen: 70.6%; and (PD-L1≥1%)/(PD-L1 < 1%)/not evaluable: 58.8%/35.3%/5.9%.At a minimum follow-up of 36 months, ORR and DCR were 29.4% [n=10, 95% CI: 16.8–46.2] and 67.6% (n=23,95% CI: 50.8–80.9), respectively. Median DOR was 11.1 months (95% CI: 3.5–28.6+). At the data cutoff date (November 2019), seven patients were alive. Two- and three-year OS rates were 35.3% (95% CI: 19.9–51.0) and 23.5% (95% CI: 11.1–38.6), respectively. Furthermore, two- and three-year PFS rates were 17.0% (95% CI: 6.3–32.0) and 12.7% (95% CI: 3.7–27.6), respectively.Overall, 26 patients (76.5%) experienced treatment-related adverse events (TRAEs) and 11 (32.4%) were grade 3-4. The most commonly reported TRAEs were skin disorders (n=6,17.6%), elevated lipase (n=5,14.7%), elevated amylase levels (n=4,11.8%), and diarrhea (n=4,11.8%).
Conclusions
Nivolumab showed durable long-term efficacy and a manageable safety profile in Japanese patients with MPM receiving second- and third-line treatment.
Clinical trial identification
JapicCTI-163247.
Legal entity responsible for the study
Ono Pharmaceutical Co. Ltd.
Funding
Ono Pharmaceutical Co. Ltd., Bristol-Myers Squibb Company.
Disclosure
H. Hayashi: Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): AstraZeneca; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Boehringer Ingelheim Japan Inc.; Advisory/Consultancy, Speaker Bureau/Expert testimony: Eli Lilly Japan K.K.; Speaker Bureau/Expert testimony, Research grant/Funding (self): Ono Pharmaceutical Co. Ltd.; Speaker Bureau/Expert testimony: Taiho Pharmaceutical Co. Ltd.; Speaker Bureau/Expert testimony: Kyowa Hakko Kirin Co. Ltd.; Speaker Bureau/Expert testimony: Pfizer Japan Inc.; Advisory/Consultancy: Chugai Pharmaceutical Co. Ltd.; Advisory/Consultancy: MerckBiopharma. T. Kijima: Honoraria (self): Ono Pharmaceutical Co. Ltd. K. Aoe: Speaker Bureau/Expert testimony, Research grant/Funding (institution): Ono Pharmaceutical Co. Ltd.; Speaker Bureau/Expert testimony, Research grant/Funding (institution): Bristol-Myers Squibb Company; Speaker Bureau/Expert testimony, Research grant/Funding (institution): Merck Sharp & Dohme Corp.; Research grant/Funding (institution): Novartis Pharma K.K.; Research grant/Funding (institution): AstraZeneca K.K.; Research grant/Funding (institution): Pfizer Inc. T. Kato: Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): AstraZeneca K.K.; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Merck Sharp & Dohme Corp.; Honoraria (self), Research grant/Funding (institution): Pfizer Inc.; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Eli Lilly K.K.; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Merck Biopharma Co., Ltd; Honoraria (self), Research grant/Funding (institution): Chugai Pharmaceutical Co., Ltd.; Honoraria (self), Research grant/Funding (institution): Ono Pharmaceutical Co., Ltd.; Honoraria (self): Nippon Boehringer Ingelheim Co., Ltd.; Honoraria (self): Takeda Pharmaceutical Co., Ltd.; Honoraria (self), Research grant/Funding (institution): AbbVie GK; Honoraria (self), Research grant/Funding (institution): Novartis Pharma K.K.; Honoraria (self), Research grant/Funding (institution): Taiho Phamaceutical Co., Ltd.; Honoraria (self): Daiichi Sankyo Co., Ltd.; Honoraria (self): Shionogi & Co., Ltd.; Honoraria (self): Nippon Kayaku Co., Ltd.; Research grant/Funding (institution): Regeneron Pharmaceuticals, Inc; Research grant/Funding (institution): Amgen inc.; Honoraria (self), Research grant/Funding (institution): Bristol-Myers Squibb K.K.. N. Fujimoto: Honoraria (self): Ono Pharmaceutical Co., Ltd.; Honoraria (self): Bristol-Myers Squibb K.K.; Honoraria (self): Daiichi Sankyo Co., Ltd. K. Nakagawa: Honoraria (self), Advisory/Consultancy: KYORIN Pharmaceutical Co., Ltd.; Honoraria (self), Advisory/Consultancy: Pfizer Japan Inc.; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Ono Pharmaceutical Co.,Ltd.; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Eli Lilly Japan K.K.; Honoraria (self): Roche Diagnostics K.K; Honoraria (self): Nippon Kayaku Co.,Ltd; Honoraria (self), Research grant/Funding (institution): Bayer Yakuhin, Ltd; Honoraria (self), Research grant/Funding (institution): AstraZeneca K.K.; Honoraria (self), Research grant/Funding (institution): Chugai Pharmaceutical Co., Ltd.; Honoraria (self), Research grant/Funding (institution): MSD K.K.; Honoraria (self), Research grant/Funding (institution): Nippon Boehringer Ingelheim Co.,Ltd.; Honoraria (self): Merck Biopharma Co., Ltd.; Honoraria (self): AbbVie Inc.; Honoraria (self), Research grant/Funding (institution): Taiho Pharmaceutical Co.,Ltd.; Honoraria (self), Research grant/Funding (institution): Novartis Pharma K.K.; Honoraria (self): Medical Review Co., Ltd.; Honoraria (self), Research grant/Funding (institution): Bristol-Myers Squibb Company; Honoraria (self): Medical Mobile Communications co., Ltd; Honoraria (self): 3H Clinical Trial Inc.; Honoraria (self): YODOSHA CO., LTD.; Research grant/Funding (institution): Takeda Pharmaceutical Co.,Ltd.; Research grant/Funding (institution): Daiichi Sankyo Co., Ltd.; Research grant/Funding (institution): Eisai Co., Ltd.; Research grant/Funding (institution): EPS Corporation.; Research grant/Funding (institution): Syneos Health.; Research grant/Funding (institution): Pfizer R&D Japan G.K.; Research grant/Funding (institution): IQVIA Services JAPAN K.K.; Research grant/Funding (institution): AbbVie Inc.; Research grant/Funding (institution): A2 Healthcare Corp.; Research grant/Funding (institution): SymBio Pharmaceuticals Limited.; Research grant/Funding (institution): EPS International Co.,Ltd.; Research grant/Funding (institution): Pfizer Japan Inc.; Research grant/Funding (institution): Otsuka Pharmaceutical Co., Ltd. Y. Takeda: Research grant/Funding (institution): Taiho Phamaceutical Co., Ltd.; Research grant/Funding (institution): Ono Pharmaceutical Co., Ltd. T. Hida: Honoraria (self): Ono Pharmaceutical Co., Ltd.; Honoraria (self): Chugai Pharmaceutical Co., Ltd.; Honoraria (self): AstraZeneca K.K.; Honoraria (self): Bristol-Myers Squibb K.K.; Honoraria (self): MSD. J. Hirano: Full/Part-time employment: Ono Pharmaceutical Co., Ltd. Y. Namba: Full/Part-time employment: Ono Pharmaceutical Co., Ltd.. Y. Ohe: Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): AstraZeneca; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Chugai Pharmaceutical Co., Ltd.; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): ONO; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Bristol-Myers Squibb K.K.; Advisory/Consultancy, Research grant/Funding (institution): Kyorin; Advisory/Consultancy: Celltrion; Advisory/Consultancy: Amgen; Honoraria (self), Advisory/Consultancy: Nippon Kayaku; Honoraria (institution), Research grant/Funding (institution): Eli Lilly; Honoraria (self): Boehringer Ingelheim; Honoraria (self): Bayer; Honoraria (self): Kyowa Hakko Kirin; Research grant/Funding (institution): Dainippon- Sumitomo; Honoraria (self), Research grant/Funding (institution): Pfizer; Honoraria (self), Research grant/Funding (institution): Taiho; Research grant/Funding (institution): Novartis; Research grant/Funding (institution): Kissei; Research grant/Funding (institution): Ignyta; Research grant/Funding (institution): Takeda; Research grant/Funding (institution): Daiichi Sankyo; Research grant/Funding (institution): Janssen; Research grant/Funding (institution): Loxo; Honoraria (self): MSD. All other authors have declared no conflicts of interest.
1896MO - Volumetric PET response assessment outperforms conventional criteria in patients receiving high-dose pembrolizumab for malignant mesothelioma
- Daniel C. C. Christoph (Essen, Germany)
Abstract
Background
Fixed-dose pembrolizumab (200 mg abs., d1, q3w) for the treatment of malignant pleural mesothelioma did not result in survival benefit in the phase 3 PROMISE-meso trial compared to 2nd-line chemotherapy. Due to lack of validated imaging response criteria, responder-subgroups with potential survival benefit have not yet been identified. Here, we administered high-dose pembrolizumab (10 mg/kg, d1, q2w) considering the KEYNOTE-028 trial and assessed the prognostic value of PET metabolic response in patients with chemotherapy-resistant malignant mesothelioma of the pleura or peritoneum.
Methods
Data from 27 patients with baseline and follow-up 18F-FDG PET/CT imaging were retrospectively analyzed. RECIST v1.1, mRECIST, PERCISTSULpeak and PERCISTMTV were used separately to categorize responders in CT and PET imaging studies. Progression-free survival (PFS) and overall survival (OS) of responders were compared to non-responders using Kaplan-Meier and log-rank analyses. Programmed Cell Death Protein 1 (PD-L1) expression status was assessed and its association with outcome was investigated.
Results
27 patients had 18F-FDG-PET/CT imaging at baseline and after at least 4 cycles pembrolizumab. Median PFS and OS were 3.4 and 15.1 months, respectively. Response rates were 7%, 7%, 30%, and 30% based on RECIST v1.1, mRECIST, PERCISTSULpeak, and PERCISTMTV response criteria, respectively. Response according to PERCISTMTV predicted prolonged OS or PFS (p < 0.01), whereas all other imaging criteria and PD-L1 expression did not.
Conclusions
18F-FDG PET metabolic volume response predicts survival in patients with malignant mesothelioma receiving high-dose pembrolizumab. These results should prompt inclusion of PET response assessment in future phase 3 clinical trials.
Legal entity responsible for the study
PD Dr. med. Daniel C. Christoph.
Funding
Has not received any funding.
Disclosure
D.C.C. Christoph: Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: AstraZeneca; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Bayer; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Boehringer Ingelheim; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Bristol-Myers Squibb; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Chugai; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Merck, Sharp & Dohme; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Novartis; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Pfizer; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Roche; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Takeda. W.P. Fendler: Advisory/Consultancy: BTG; Advisory/Consultancy: Endocyte; Advisory/Consultancy: Ipsen; Honoraria (self): RadioMedix. L. Kessler: Honoraria (self): Sanofi. M. Metzenmacher: Honoraria (self): Boehringer Ingelheim; Honoraria (self): Bristol-Myers Squibb; Honoraria (self): Merck, Sharp & Dohme; Honoraria (self): Roche; Honoraria (self): Takeda. T. Hager: Honoraria (self): Bristol-Myers Squibb; Honoraria (self): Chugai; Honoraria (self): Merck, Sharp & Dohme; Honoraria (self): Roche. K. Herrmann: Non-remunerated activity/ies: ABX; Honoraria (self): Adacap; Honoraria (self): Amgen; Honoraria (self): Bayer; Honoraria (self), Research grant/Funding (institution): BTG; Honoraria (self): Curium; Honoraria (self): Endocyte; Honoraria (self): GE Healthcare; Honoraria (self): Ipsen; Honoraria (self): Novartis; Honoraria (self): Siemens Healthineers; Honoraria (self): Sirtex, Honoraria (self), Non-remunerated activity/ies: Sofie Biosciences; Honoraria (self): ymabs. All other authors have declared no conflicts of interest.
Invited Discussant 1895MO and 1896MO
- Oliver Gautschi (Luzern, Switzerland)
LBA49 - Durvalumab after chemoradiotherapy in stage III NSCLC: 4-year survival update from the phase III PACIFIC trial
- Corinne Faivre-Finn (Manchester, United Kingdom)
Abstract
Background
In the phase III PACIFIC trial of patients (pts) with unresectable Stage III NSCLC without disease progression after concurrent chemoradiotherapy (cCRT), durvalumab significantly improved progression-free survival (PFS; stratified HR 0.52, 95% CI 0.42–0.65; P<0.0001; median 16.8 vs 5.6 months; data cutoff [DCO], 13 Feb 2017) and overall survival (OS; stratified HR 0.68, 95% CI 0.53–0.87; P=0.0025; median not reached vs 28.7 months; DCO, 22 Mar 2018) vs placebo (pbo), with manageable safety. We report updated, exploratory analyses of survival outcomes at 4 years, including the first estimate of median OS for the durvalumab arm.
Methods
Pts with WHO PS 0/1 (any tumour PD-L1 status) who had received ≥2 cycles of platinum-based cCRT (RT dosage typically 60–66 Gy in 30–33 fractions) were enrolled and randomised (2:1), 1–42 days post-cCRT, to IV durvalumab 10 mg/kg or pbo (q2w for ≤12 months), stratified by age, sex, and smoking history. Primary endpoints were PFS (blinded independent central review; RECIST v1.1) and OS (both measured from the time of randomisation). HRs and 95% CIs were estimated using a stratified log-rank test in the ITT population. Medians and OS/PFS rates at 48 months were estimated by Kaplan–Meier method.
Results
In total, 709/713 randomised patients received durvalumab (n/N=473/476) and pbo (n/N=236/237). The last pt had completed study treatment in May 2017, almost 3 years prior to the current DCO. As of 20 Mar 2020 (current DCO; median follow up, 34.2 months [range, 0.2–64.9]), updated PFS (stratified HR 0.55, 95% CI 0.44–0.67; median 17.2 vs 5.6 months) and OS (stratified HR 0.71, 95% CI 0.57–0.88) remained consistent with previous reports. Median OS for the durvalumab arm was determined for the first time: 47.5 months (pbo, 29.1 months). The 48-month OS rates were 49.6% vs 36.3% for durvalumab vs pbo, and PFS rates were 35.3% vs 19.5% respectively. Updates to treatment effects for pt subgroups will be reported.
Conclusions
These updated analyses of PFS and OS demonstrate durable benefit with durvalumab after cCRT. Approximately half of patients randomised to durvalumab in PACIFIC remain alive at 4 years, and about a third remain both alive and progression free, almost 3 years after the last pt completed study treatment.
Clinical trial identification
NCT02125461.
Editorial acknowledgement
Medical writing support, which was in accordance with Good Publication Practice (GPP3) guidelines, was provided by Aaron Korpal, PhD, of Cirrus Communications (Manchester, UK), an Ashfield company, and was funded by AstraZeneca.
Legal entity responsible for the study
AstraZeneca.
Funding
AstraZeneca.
Disclosure
C. Faivre-Finn: Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: AstraZeneca; Research grant/Funding (institution), Travel/Accommodation/Expenses: Elekta. D. Vicente: Honoraria (self), Research grant/Funding (institution): AstraZeneca; Honoraria (self), Research grant/Funding (institution): Pfizer; Honoraria (self): Bristol-Myers Squibb; Honoraria (self), Research grant/Funding (institution): MSD; Honoraria (self), Research grant/Funding (institution): Roche. T. Kurata: Honoraria (self), Research grant/Funding (institution): AstraZeneca; Honoraria (self): Eli Lilly; Honoraria (self), Research grant/Funding (institution): MSD; Honoraria (self): Ono; Honoraria (self): Boehringer Ingelheim; Honoraria (self), Research grant/Funding (institution): Bristol-Myers Squibb; Honoraria (self), Research grant/Funding (institution): Chugai; Research grant/Funding (institution): Novartis; Research grant/Funding (institution): Takeda. D. Planchard: Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Bristol-Myers Squibb; Advisory/Consultancy: Boehringer Ingelheim; Advisory/Consultancy: Celgene; Advisory/Consultancy: Daiichi Sankyo; Advisory/Consultancy: Eli Lilly; Advisory/Consultancy: Merck; Advisory/Consultancy: Novartis; Advisory/Consultancy: Pfizer; Advisory/Consultancy: prIME Oncology; Advisory/Consultancy: Peer CME; Advisory/Consultancy: Roche; Advisory/Consultancy: Samsung. L. Paz-Ares: Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: MSD; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Bristol-Myers Squibb; Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Roche; Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: AstraZeneca; Advisory/Consultancy, Speaker Bureau/Expert testimony: Eli Lilly; Advisory/Consultancy: Merck; Advisory/Consultancy: Novartis; Advisory/Consultancy: Angem; Advisory/Consultancy: Incyte; Advisory/Consultancy: Takeda; Advisory/Consultancy: Blueprint; Advisory/Consultancy: Bayer; Leadership role: Altum Sequencing; Leadership role: Genomica; Advisory/Consultancy: PharmaMar; Advisory/Consultancy: Ipsen. J.F. Vansteenkiste: Advisory/Consultancy: Boehringer Ingelheim; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: MSD; Advisory/Consultancy: Novartis; Advisory/Consultancy: Roche; Advisory/Consultancy: Pfizer; Advisory/Consultancy: Bristol-Myers Squibb. D.R. Spigel: Honoraria (institution), Research grant/Funding (institution): AstraZeneca; Research grant/Funding (institution): Aeglea Biotherapeutics; Research grant/Funding (institution): Agios; Research grant/Funding (institution): Astellas Pharma; Research grant/Funding (institution): Bind Therapeutics; Honoraria (institution), Research grant/Funding (institution): Bristol-Myers Squibb; Honoraria (institution), Research grant/Funding (institution): Celgene; Research grant/Funding (institution): Celldex Therapeutics; Research grant/Funding (institution): Clovis; Research grant/Funding (institution): Daiichi Sankyo; Research grant/Funding (institution): Eisai; Research grant/Funding (institution): Eli Lilly; Honoraria (institution), Research grant/Funding (institution): EMD Serono; Honoraria (institution), Research grant/Funding (institution): Roche/Genentech; Research grant/Funding (institution): G1 Therapeutics; Honoraria (institution), Research grant/Funding (institution): GlaxoSmithKline; Research grant/Funding (institution): Grail; Research grant/Funding (institution): ImClone Systems; Honoraria (institution), Research grant/Funding (institution): Ipsen; Research grant/Funding (institution): Janssen; Research grant/Funding (institution): Merck; Research grant/Funding (institution): Nektar Therapeutics; Research grant/Funding (institution): Neon Therapeutics; Honoraria (institution), Research grant/Funding (institution): Novartis; Honoraria (institution), Research grant/Funding (institution): Takeda Pharmaceuticals; Research grant/Funding (institution): Tesaro; Research grant/Funding (institution): Transgene; Research grant/Funding (institution): UT Southwestern; Research grant/Funding (institution): Cyteir Therapeutics; Research grant/Funding (institution): Apollomics; Research grant/Funding (institution): Elevation Oncology; Honoraria (institution): Aptitude Health; Honoraria (institution): Bayer; Honoraria (institution): Dracen Pharmaceuticals; Honoraria (institution): Exelixis; Honoraria (institution): Iksuda Therapeutics; Honoraria (institution): Intellisphere; Honoraria (institution): Jazz Pharmaceuticals; Honoraria (institution): Mirati Therapeutics; Honoraria (institution): Molecular Templates; Honoraria (institution): Puma Biotechnology. M.C. Garassino: Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution), Non-remunerated activity/ies: Eli Lilly; Advisory/Consultancy: Boehringer Ingelheim; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Otsuka Pharma; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): AstraZeneca; Advisory/Consultancy, Research grant/Funding (institution): Novartis; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (self): Bristol-Myers Squibb; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Roche; Advisory/Consultancy, Research grant/Funding (institution), Non-remunerated activity/ies: Pfizer; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Celgene; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Incyte; Advisory/Consultancy: Inivata; Advisory/Consultancy, Speaker Bureau/Expert testimony: Takeda; Research grant/Funding (institution): Tiziana Sciences; Research grant/Funding (institution): Clovis; Research grant/Funding (institution): Merck Serono; Advisory/Consultancy, Research grant/Funding (institution): Bayer; Advisory/Consultancy, Research grant/Funding (institution), Non-remunerated activity/ies: MSD; Advisory/Consultancy, Research grant/Funding (institution): GlaxoSmithKline S.p.A.; Advisory/Consultancy: Sanofi-Aventis; Advisory/Consultancy, Research grant/Funding (institution): Spectrum Pharmaceuticals; Advisory/Consultancy, Research grant/Funding (institution): Blueprint Medicine; Advisory/Consultancy: Seattle Genetics; Advisory/Consultancy: Daiichi Sankyo; Research grant/Funding (institution): United Therapeutics Corporation; Research grant/Funding (institution): Merck KGaA; Advisory/Consultancy: Janssen. M. Reck: Honoraria (self), Advisory/Consultancy: Amgen; Honoraria (self), Advisory/Consultancy: AstraZeneca; Honoraria (self), Advisory/Consultancy: Bristol-Myers Squibb; Honoraria (self), Advisory/Consultancy: Boehringer Ingelheim; Honoraria (self), Advisory/Consultancy: Eli Lilly; Honoraria (self), Advisory/Consultancy: Merck; Honoraria (self), Advisory/Consultancy: MSD; Honoraria (self), Advisory/Consultancy: Novartis; Honoraria (self), Advisory/Consultancy: Pfizer; Honoraria (self), Advisory/Consultancy: Roche; Honoraria (self), Advisory/Consultancy: Samsung. S. Senan: Honoraria (self), Research grant/Funding (institution): AstraZeneca; Research grant/Funding (institution): ViewRay Inc.; Honoraria (self): Celgene; Honoraria (self): MSD; Honoraria (self), Research grant/Funding (institution): Varian Medical Systems. J. Naidoo: Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: AstraZeneca; Advisory/Consultancy, Research grant/Funding (institution): Roche/Genentech; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Bristol-Myers Squibb; Research grant/Funding (institution): Merck. A. Rimner: Research grant/Funding (institution): Varian Medical Systems; Honoraria (self), Research grant/Funding (institution): AstraZeneca; Honoraria (self), Research grant/Funding (institution): Merck; Research grant/Funding (institution): Boehringer Ingelheim; Research grant/Funding (institution): Pfizer; Honoraria (self): Research to Practice; Honoraria (self): Cybrexa; Honoraria (self): More Health; Non-remunerated activity/ies: Philips/Elektra. Y-L. Wu: Speaker Bureau/Expert testimony, Research grant/Funding (institution): AstraZeneca; Speaker Bureau/Expert testimony: Boehringer Ingelheim; Speaker Bureau/Expert testimony, Research grant/Funding (institution): Bristol-Myers Squibb; Speaker Bureau/Expert testimony: Eli Lilly; Speaker Bureau/Expert testimony: MSD; Speaker Bureau/Expert testimony, Research grant/Funding (institution): Pfizer; Speaker Bureau/Expert testimony: Sanofi. J.E. Gray: Advisory/Consultancy: AstraZeneca; Research grant/Funding (institution): Genentech; Advisory/Consultancy, Research grant/Funding (institution): Merck; Advisory/Consultancy, Research grant/Funding (institution): Bristol-Myers Squibb; Advisory/Consultancy, Research grant/Funding (institution): Merck KGaA; Advisory/Consultancy, Research grant/Funding (institution): Novartis; Research grant/Funding (institution): Boehringer Ingelheim. M. Özgüroğlu: Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Janssen; Honoraria (self), Advisory/Consultancy: Sanofi; Honoraria (self), Honoraria (institution), Advisory/Consultancy, Speaker Bureau/Expert testimony: Astellas; Honoraria (self): Novartis; Honoraria (self): Roche; Travel/Accommodation/Expenses: Bristol-Myers Squibb. K.H. Lee: Advisory/Consultancy: Bristol-Myers Squibb; Advisory/Consultancy: MSD; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Pfizer. M. Newton: Full/Part-time employment: AstraZeneca. L. Wang: Full/Part-time employment: AstraZeneca. P. Thiyagarajah: Shareholder/Stockholder/Stock options, Full/Part-time employment: AstraZeneca. S.J. Antonia: Advisory/Consultancy, Travel/Accommodation/Expenses: Bristol-Myers Squibb; Advisory/Consultancy: CBMG; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Memgen; Advisory/Consultancy, Travel/Accommodation/Expenses: RAPT; Advisory/Consultancy: Venn; Advisory/Consultancy, Travel/Accommodation/Expenses: Achilles Therapeutics; Advisory/Consultancy, Travel/Accommodation/Expenses: Celsius; Advisory/Consultancy: Samyang Biopharma; Advisory/Consultancy, Travel/Accommodation/Expenses: GlaxoSmithKline; Advisory/Consultancy, Travel/Accommodation/Expenses: Amgen; Travel/Accommodation/Expenses: Merck; Research grant/Funding (institution): Novartis.
1236MO - A single-arm phase II study of gefitinib with concurrent thoracic radiotherapy in unresectable locally-advanced non-small cell lung cancer patients with EGFR mutation (West Japan Oncology Group 6911L)
- Junichi Shimizu (Nagoya, Japan)
Abstract
Background
Epidermal growth factor receptor mutation (EGFR)-tyrosine kinase inhibitor plays a key role in EGFR-mutated, metastatic non-small cell lung cancer (NSCLC). However, it has not been explored whether EGFR-TKI plus concurrent thoracic radiotherapy may be effective in locally-advanced NSCLC patients with EGFR mutation.
Methods
Chemotherapy-naïve, locally-advanced NSCLC patients with EGFR mutation were enrolled. Patients were treated with gefitinib (250mg/day, p.o. for 2 years) plus concurrent thoracic radiotherapy (64Gy/32frs). Primary endpoint was progression-free survival (PFS) at 2 years. Secondary endpoints consisted of overall response rate (ORR), PFS, overall survival (OS) and safety. Based on the hypothesis that this treatment will improve PFS rate at 2 years from 20 to 40% (0.05 of one-sided α and 0.25 of β), 27 patients are required (Trial Identifier, UMIN000008366).
Results
Between Aug 2012 and Nov 2017, 28 patients were enrolled and 27 were eligible. Of those, median age was 67 (range, 45-74); male/female 7/20; never/current or former smoker 15/12; ECOG performance status 0/1 19/8; EGFR exon 19 deletion/exon 21 L858R 13/14; c-stage IIIA/IIIB 14/13. PFS rate at 2 years by independent review was 29.6% (one-sided 95% confidence interval [CI]: 17.6%-). ORR was 81.5% (95%CI: 66.5% to not reached), median PFS was 28.6 months (95%CI: 12.0 to 24.5 months), and median OS was 61.1 months (95%CI: 38.1 months to not reached). Adverse events ≥Gr 3 were fatigue, skin reaction and appetite loss (3.7%, respectively). Pneumonitis was frequently observed, but all events were mild (Gr1 59.2% and Gr2 29.6%).
Conclusions
Among unresectable locally-advanced NSCLC patients with EGFR mutation, gefitinib with concurrent thoracic radiotherapy did not improve PFS rate at 2 years.
Clinical trial identification
Trial Identifier, UMIN000008366.
Legal entity responsible for the study
West Japan Oncology Group.
Funding
Astrazeneca.
Disclosure
J. Shimizu: Honoraria (self): AstraZeneca K.K.; Honoraria (self): MSD; Honoraria (self): Ono Pharmaceutical; Honoraria (self): Chugai Pharmaceutical; Honoraria (self): Taiho Pharmaceutical. H. Akamatsu: Honoraria (self): AstraZeneca K.K.; Honoraria (self): Boehringer Ingelheim,; Honoraria (self), Research grant/Funding (self): Chugai Pharmaceutical; Honoraria (self), Research grant/Funding (self): Eli Lilly; Honoraria (self), Research grant/Funding (self): MSD K.K.; Honoraria (self): Ono Pharmaceutical Co., Ltd.; Honoraria (self): Taiho Pharmaceutical; Honoraria (self): Bristol-Myers Squibb; Honoraria (self): Novartis. H. Murakami: Honoraria (self), Research grant/Funding (self): AstraZeneca K.K.; Honoraria (self), Research grant/Funding (self): Chugai Pharmaceutical; Honoraria (self), Research grant/Funding (self): Eli Lilly; Honoraria (self), Research grant/Funding (self): Taiho Pharmaceutical; Honoraria (self), Research grant/Funding (self): Takeda; Research grant/Funding (self): AbbVie; Research grant/Funding (self): Daiichi Sankyo; Research grant/Funding (self): IQvia; Honoraria (self): Ono Pharmaceutical; Honoraria (self): Bristol-Myers Squibb Japan; Honoraria (self): MSD. H. Harada: Honoraria (self): AstraZeneca K.K.; Honoraria (self): BrainLab; Honoraria (self): Chugai Pharmaceutical; Honoraria (self): Merck Biopharma; Honoraria (self): Daiichi Sankyo. H. Hayashi: Honoraria (self), Research grant/Funding (self): AstraZeneca K.K.; Honoraria (self), Research grant/Funding (self): Boehringer Ingelheim,; Honoraria (self): Bristol-Myers Squibb Co., Ltd.; Honoraria (self): Chugai Pharmaceutical Co. Ltd.; Honoraria (self): Eli Lilly Japan K.K.; Honoraria (self): MSD K.K.; Honoraria (self), Research grant/Funding (self): Ono Pharmaceutical Co. Ltd.; Honoraria (self): Pfizer Japan Inc.; Honoraria (self): Shanghai Haihe Biopharm; Honoraria (self): Kyorin pharmaceutical co. ltd; Honoraria (self): Novartis Pharma K.K.; Honoraria (self): Taiho Pharmaceutical Co. Ltd. H. Daga: Honoraria (self), Research grant/Funding (self): AstraZeneca K.K.; Honoraria (self): Boehringer Ingelheim,; Honoraria (self), Research grant/Funding (self): Chugai Pharmaceutical; Honoraria (self), Research grant/Funding (self): Eli Lilly; Honoraria (self): MSD K.K.; Honoraria (self): Ono Pharmaceutical Co.,Ltd.; Honoraria (self): Taiho Pharmaceutical; Research grant/Funding (self): Pfizer. Y.H. Kim: Honoraria (self): AstraZeneca K.K.; Honoraria (self): Chugai Pharmaceutical; Honoraria (self), Research grant/Funding (self): Ono Pharmaceutical Co. Ltd.; Honoraria (self): Bristol-Myers Squibb Co. Ltd.; Honoraria (self): MSD K.K.; Honoraria (self), Research grant/Funding (self): Taiho Pharmaceutical Co. Ltd.; Honoraria (self): Pfizer. T. Kato: Honoraria (self), Research grant/Funding (self): AbbVie; Honoraria (self), Research grant/Funding (self): AstraZeneca; Honoraria (self), Research grant/Funding (self): Boehringer Ingelheim; Honoraria (self), Research grant/Funding (self): Bristol-Myers Squibb; Honoraria (self), Research grant/Funding (self): Chugai Pharmaceutical; Honoraria (self), Research grant/Funding (self): Eli Lilly; Honoraria (self), Research grant/Funding (self): Merck Biopharma; Honoraria (self), Research grant/Funding (self): MSD; Honoraria (self), Research grant/Funding (self): Novartis; Honoraria (self), Research grant/Funding (self): Ono Pharmaceutical; Honoraria (self), Research grant/Funding (self): Pfizer; Honoraria (self), Research grant/Funding (self): Taiho Pharmaceutical; Research grant/Funding (self): Amgen; Research grant/Funding (self): Astellas; Research grant/Funding (self): Kyowa-Kirin; Research grant/Funding (self): KYORIN Pharmaceutical Co., Ltd.; Research grant/Funding (self): Regeneron; Honoraria (self): Daiichi Sankyo; Honoraria (self): Nippon Kayaku Co., Ltd.; Honoraria (self): F. Hoffmann-La Roche; Honoraria (self): Nitto Denko; Honoraria (self): Sumitomo Dainippon; Honoraria (self): Shionogi; Honoraria (self): Takeda. N. Yamamoto: Honoraria (self), Research grant/Funding (self): AstraZeneca K.K.; Honoraria (self), Research grant/Funding (self): Boehringer Ingelheim,; Honoraria (self), Research grant/Funding (self): Chugai Pharmaceutical; Honoraria (self), Research grant/Funding (self): Eli Lilly; Honoraria (self), Research grant/Funding (self): MSD K.K.; Honoraria (self): Novartis; Honoraria (self), Research grant/Funding (self): Ono Pharmaceutical; Honoraria (self), Research grant/Funding (self): Pfizer; Research grant/Funding (self): Astellas Pharma Inc; Research grant/Funding (self): Bristol-Myers Squibb Japan; Research grant/Funding (self): Daiichi Sankyo; Research grant/Funding (self): Takeda Pharmaceutical; Research grant/Funding (self): Taiho Pharmaceutical; Research grant/Funding (self): Terumo Corporation; Honoraria (self): Toppan Printing Co., Ltd. K. Nakagawa: Honoraria (self), Research grant/Funding (self): AstraZeneca K.K.; Honoraria (self): Nichi-Iko Pharmaceutical Co., Ltd.; Honoraria (self), Research grant/Funding (self): Astellas Pharma Inc.; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): Takeda Pharmaceutical Co., Ltd.; Honoraria (self), Research grant/Funding (self): MSD K.K.; Honoraria (self), Research grant/Funding (self): Taiho Pharmaceutical Co., Ltd.; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): Ono Pharmaceutical Co., Ltd.; Honoraria (self), Research grant/Funding (self): Bristol-Myers Squibb Company; Honoraria (self), Research grant/Funding (self): Nippon Boehringer Ingelheim Co., Ltd.; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): Eli Lilly Japan K.K.; Honoraria (self), Research grant/Funding (self): Novartis Pharma K.K.; Honoraria (self): SymBio Pharmaceuticals Limited; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): Pfizer Japan Inc.; Honoraria (self), Research grant/Funding (self): Chugai Pharmaceutical Co., Ltd.; Honoraria (self), Research grant/Funding (self): Daiichi Sankyo Co., Ltd.; Honoraria (self), Advisory/Consultancy: KYORIN Pharmaceutical Co., Ltd.; Honoraria (self): Thermo Fisher Scientific K.K.; Honoraria (self): Roche Diagnostics K.K.; Honoraria (self): Nippon Kayaku Co., Ltd.; Honoraria (self), Research grant/Funding (self): Bayer Yakuhin, Ltd.; Honoraria (self), Research grant/Funding (self): Merck Biopharma Co., Ltd.; Honoraria (self), Research grant/Funding (self): AbbVie Inc.; Research grant/Funding (self): Kissei Pharmaceutical Co., Ltd.; Research grant/Funding (self): Kyowa Hakko Kirin Co., Ltd; Research grant/Funding (self): Merck Serono Co., Ltd; Research grant/Funding (self): Eisai Co., Ltd.; Research grant/Funding (self): SymBio Pharmaceuticals Limited; Research grant/Funding (self): Otsuka Pharmaceutical Co., Ltd. All other authors have declared no conflicts of interest.
1237MO - SAKK 16/14: Anti-PD-L1 antibody durvalumab in addition to neoadjuvant chemotherapy in patients with stage IIIA (N2) non-small cell lung cancer (NSCLC) – A multicenter single-arm phase II trial
- Sacha I. Rothschild (Basel, Switzerland)
Abstract
Background
For patients with resectable stage IIIA(N2) non-small cell lung cancer (NSCLC) neoadjuvant chemotherapy with 3 cycles cisplatin (cis)/docetaxel (doce) followed by surgery is an accepted standard of care achieving a 1-year event-free survival (EFS) of 48%. PD-(L)1 inhibitors have recently shown high response rates in resectable NSCLC.
Methods
Neoadjuvant treatment consisted of 3 cycles of cis 100 mg/m2 and doce 85 mg/m2 q3w followed by 2 cycles of durvalumab 750 mg q2w. Durvalumab was continued after surgery for 1 year. The primary endpoint is EFS at 1 year. The hypothesis for statistical considerations was an improvement of EFS at 1 year from 48% to 65%.
Results
Sixty-eight patients were included. Radiographic response rate was 44.8% (95%CI: 32.6-57.4) after neoadjuvant chemotherapy (CR: 4.5%, PR: 40.3%, SD: 44.8%) and 58.1% (95%CI: 44.8-70.5) after additional neoadjuvant immunotherapy (CR: 6.5%, PR: 51.6%, SD: 25.8%). Of the 55 resected patients, 10 patients (18.2%) had a pathological complete response and 33 patients (60.0%) a major pathological response defined as ≤10% viable tumor cells by central pathology review. Postoperative nodal down-staging was observed in 37 patients (67.3%). 1-year EFS was 73.3% (90%CI: 60.1-82.7). At the time of the analysis, median EFS was not reached. After a median follow up of 28 months, median OS was not reached. Thirteen patients had died with disease progression/disease recurrence as the most frequent reason (11 patients). 59 patients (88.1%) had an AE grade ≥3 including two fatal cases (one postoperative bleeding complication and one respiratory failure). Results for PD-L1 expression and tumor mutational burden will be presented during the meeting.
Conclusions
This is to our knowledge the largest study of patients with resectable stage IIIA(N2) NSCLC investigating perioperative immune checkpoint inhibitor therapy. The addition of perioperative durvalumab to standard of care cis/doce is safe and results in a encouraging 1-year EFS rate exceeding historical data of chemotherapy alone and achieves a high major pathological response rate.
Clinical trial identification
NCT02572843.
Legal entity responsible for the study
Swiss Group for Clinical Cancer Research SAKK.
Funding
Foundation or academic group WITH funding from a pharma, biotech, or other commercial company - AstraZeneca.
Disclosure
S.I. Rothschild: Advisory/Consultancy, Research grant/Funding (institution): AstraZeneca; Advisory/Consultancy, Research grant/Funding (self): BMS; Advisory/Consultancy, Research grant/Funding (institution): Merck Serono; Advisory/Consultancy: Boehringer Ingelheim; Advisory/Consultancy: Pfizer; Advisory/Consultancy: Eisai; Advisory/Consultancy: Eli Lilly; Advisory/Consultancy: MSD; Advisory/Consultancy: Novartis; Honoraria (institution), Advisory/Consultancy: Roche; Advisory/Consultancy: Takeda. A. Zippelius: Advisory/Consultancy, Research grant/Funding (institution): Roche; Advisory/Consultancy: MSD; Advisory/Consultancy: BMS; Research grant/Funding (institution): Beyondsprings; Research grant/Funding (institution): Secarna; Research grant/Funding (institution): Crescendo. S. Savic Prince: Advisory/Consultancy: MSD; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Boehringer Ingelheim; Advisory/Consultancy: Roche; Advisory/Consultancy: Pfizer; Advisory/Consultancy: Thermo Fisher Scientific. D. Betticher: Advisory/Consultancy: MSD; Advisory/Consultancy: Roche; Advisory/Consultancy: Pfizer; Advisory/Consultancy: Janssen-Cilag; Advisory/Consultancy: Novartis. M. Früh: Advisory/Consultancy: BMS; Advisory/Consultancy: MSD; Advisory/Consultancy, Research grant/Funding (institution): AstraZeneca; Advisory/Consultancy: Boehringer Ingelheim; Advisory/Consultancy: Roche; Advisory/Consultancy: Takeda. M. Joerger: Non-remunerated activity/ies: ESMO Press & Media Affairs Committee. C. Britschgi: Advisory/Consultancy, Travel/Accommodation/Expenses: AstraZeneca; Advisory/Consultancy: Pfizer; Advisory/Consultancy: Roche; Advisory/Consultancy, Travel/Accommodation/Expenses: Takeda; Advisory/Consultancy: Janssen-Cilag; Advisory/Consultancy: Boehringer Ingelheim. S. Peters: Advisory/Consultancy: AbbVie; Advisory/Consultancy: Amgen; Honoraria (institution), Advisory/Consultancy, Research grant/Funding (institution): AstraZeneca; Advisory/Consultancy: Bayer; Advisory/Consultancy: Biocartis; Advisory/Consultancy: Bioinvent; Advisory/Consultancy: Blueprint Medicines; Honoraria (institution), Advisory/Consultancy, Research grant/Funding (institution): Boehringer Ingelheim; Honoraria (institution), Advisory/Consultancy, Research grant/Funding (institution): BMS; Advisory/Consultancy, Research grant/Funding (institution): Clovis; Advisory/Consultancy: Daiichi Sankyo; Advisory/Consultancy: Debiopharm; Honoraria (institution), Advisory/Consultancy: Eli Lilly; Honoraria (institution), Advisory/Consultancy, Research grant/Funding (institution): F. Hoffmann-La Roche; Advisory/Consultancy: Foundation Medicine; Honoraria (institution), Advisory/Consultancy, Research grant/Funding (institution): Illumina; Advisory/Consultancy: Janssen; Honoraria (institution), Advisory/Consultancy, Research grant/Funding (institution): MSD; Advisory/Consultancy, Research grant/Funding (institution): Merck Serono; Advisory/Consultancy: Merrimack; Honoraria (institution), Advisory/Consultancy, Research grant/Funding (institution): Novartis; Advisory/Consultancy: Pharma Mar; Honoraria (institution), Advisory/Consultancy, Research grant/Funding (institution): Pfizer; Advisory/Consultancy: Regeneron; Honoraria (institution), Advisory/Consultancy: Sanofi; Advisory/Consultancy: Seattle Genetics; Honoraria (institution), Advisory/Consultancy: Takeda; Advisory/Consultancy: Vaccibody; Research grant/Funding (institution): Amgen; Research grant/Funding (institution): Biodesix. M.T. Mark: Advisory/Consultancy: BMS; Advisory/Consultancy: Roche; Advisory/Consultancy, Research grant/Funding (institution): AstraZeneca; Advisory/Consultancy: MSD; Advisory/Consultancy: Takeda. W. Janthur: Honoraria (self), Advisory/Consultancy: Roche; Advisory/Consultancy: Boehringer Ingelheim; Advisory/Consultancy: Takeda; Honoraria (self), Advisory/Consultancy: MSD; Advisory/Consultancy: Novartis. P.R. Froesch: Advisory/Consultancy: Roche; Advisory/Consultancy: Takeda; Advisory/Consultancy: Boehringer Ingelheim; Advisory/Consultancy: BMS; Advisory/Consultancy: Pfizer. M. Pless: Advisory/Consultancy: Abbvie; Advisory/Consultancy, Travel/Accommodation/Expenses: AstraZeneca; Advisory/Consultancy, Travel/Accommodation/Expenses: Boehringer Ingelheim; Advisory/Consultancy, Travel/Accommodation/Expenses: BMS; Advisory/Consultancy: Eisai; Advisory/Consultancy: MSD; Advisory/Consultancy: Novartis; Advisory/Consultancy: Pfizer; Advisory/Consultancy: Roche; Advisory/Consultancy: Takeda; Advisory/Consultancy: MSD; Travel/Accommodation/Expenses: Vifor; Honoraria (institution): Janssen-Cilag.
Invited Discussant LBA49, 1236MO and 1237MO
- Martin Sebastian (Frankfurt am Main, Germany)