- P. Garrido Lopez (Madrid, Spain)
- J. Wolf (Cologne, Germany)
LBA1_PR - Nivolumab (nivo) plus ipilimumab (ipi), nivo, or placebo (pbo) as maintenance therapy in patients (pts) with extensive disease small cell lung cancer (ED-SCLC) after first-line (1L) platinum-based chemotherapy (chemo): Results from the double-blind, randomized phase III CheckMate 451 study
- T. Owonikoko (Atlanta, GA, United States of America)
- T. Owonikoko (Atlanta, GA, United States of America)
- H. Kim (Seoul, Korea, Republic of)
- R. Govindan (St. Louis, MO, United States of America)
- N. Ready (Durham, NC, United States of America)
- M. Reck (Grosshansdorf, Germany)
- S. Peters (Lausanne, Switzerland)
- S. Dakhil (Wichita, KS, United States of America)
- A. Navarro (Barcelona, Spain)
- J. Rodriguez-Cid (Mexico City, Mexico)
- M. Schenker (Craiova, Dolj, Romania)
- J. Lee (Seoul, Korea, Republic of)
- V. Gutierrez (Malaga, Spain)
- I. Percent (Punta Gorda, FL, United States of America)
- D. Morgensztern (St. Louis, MO, United States of America)
- J. Fairchild (Princeton, NJ, United States of America)
- C. Baudelet (Princeton, NJ, United States of America)
- K. Park (Seoul, Korea, Republic of)
Abstract
Background
In pts with ED-SCLC, response rates to 1L platinum-based chemo are high but lack durability. Treatments (txs) that prolong response duration and improve survival are needed. CheckMate 451 (NCT02538666) is a global, double-blind, phase 3 study of nivo+ipi or nivo vs pbo as maintenance therapy in pts with ED-SCLC who did not progress on 1L platinum-based chemo.
Methods
Pts (N = 834) with ED-SCLC, ECOG performance status (PS) ≤ 1 and response or stable disease after 4 cycles of 1L platinum-based chemo were randomized 1:1:1 (3–9 weeks from last dose of 1L chemo or 3–11 weeks for pts who received prophylactic cranial irradiation [PCI]) to nivo 1 mg/kg + ipi 3 mg/kg Q3W intravenously (IV; 4 doses followed by nivo 240 mg Q2W IV; n = 279), nivo 240 mg Q2W IV (n = 280), or pbo (n = 275), stratified by PS, sex and prior PCI. Pts were treated up to 2 years or until progression or unacceptable toxicity. Primary endpoint was overall survival (OS) for nivo+ipi vs pbo. Secondary endpoints included OS for nivo vs pbo and progression-free survival (PFS) per blinded independent central review for nivo+ipi vs pbo and nivo vs pbo.
Results
Minimum study follow-up was 9 months. Baseline characteristics were balanced between arms. OS was not significantly prolonged with nivo+ipi vs pbo (HR, 0.92; 95% CI 0.75–1.12; P = 0.3693). OS was also not prolonged for nivo vs pbo (HR, 0.84; 95% CI 0.69–1.02), although not formally tested due to statistical hierarchy. PFS HRs vs pbo were: nivo+ipi, 0.72 (0.60–0.87); nivo, 0.67 (0.56–0.81). Rates of all-grade (grade 3–4) tx-related adverse events were: nivo+ipi, 86% (52%); nivo, 61% (12%); pbo, 50% (8%). Rates of discontinuation due to tx toxicity were: nivo+ipi, 31%; nivo, 9%; pbo, <1%. Tx-related deaths were: nivo+ipi, 7 (2.5%); nivo, 1 (<1%); pbo, 1 (<1%).
Conclusions
In CheckMate 451, maintenance therapy with nivo+ipi (primary endpoint) or nivo did not prolong OS vs pbo for ED-SCLC patients who did not progress on 1L chemo. Safety profiles of nivo+ipi and nivo were consistent with previous reports at this dose/schedule in SCLC.
Clinical trial identification
NCT02538666; Release date: 2 September 2015.
Editorial acknowledgement
Writing and editorial assistance was provided by Cristina Tomas, PhD, of Caudex and funded by Bristol-Myers Squibb.
Legal entity responsible for the study
Bristol-Myers Squibb.
Funding
Bristol-Myers Squibb.
Disclosure
T.K. Owonikoko: Research support: AbbVie, Adaptimmune, Amgen, AstraZeneca, Bristol-Myers Squibb, Corvus, G1 Therapeutics, Novartis, Pfizer, Regeneron/Sanofi; Advisory board: AbbVie, Amgen, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Lilly/Armo, PharmaMar, Xcovery; IRC/DSMB: EMD Serono, Roche/Genentech; Co-founder: Cambium Oncology. H.R. Kim: Speakers bureau, honoraria: AstraZeneca, ONO/Bristol-Myers Squibb; Consultant: Roche. R. Govindan: Consultant/advisory committees: AbbVie, Adaptimmune, AstraZeneca, Celgene, Ignyta, Inivata, Merck, Nektar, Pfizer, Roche. N. Ready: Advisor: AbbVie, G1 therapeutics, Merck, Novartis; Advisor/speaker: Bristol-Myers Squibb, Celgene; Education: AstraZeneca, EMD Serrano, Tesaro. M. Reck: Honoraria for lectures and consultancy: AbbVie, Amgen, AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Lilly, Merck, MSD, Novartis, Pfizer, Roche. S. Peters: Honoraria, education grants, consultancy, attended advisory boards, and/or provided lectures: AbbVie, Amgen, AstraZeneca, Bayer, Biocartis, Boehringer Ingelheim, Bristol-Myers Squibb, Clovis, Daiichi Sankyo, Debiopharm, Eli Lilly, F. Hoffmann-La Roche, Foundation Medicine, Illumina, Janssen, Merck Sharp and Dohme, Merck Serono, Merrimack, Novartis, PharmaMar, Pfizer, Regeneron, Sanofi, Seattle Genetics, Takeda. A. Navarro: Advisory role: Boehringer Ingelheim, Bristol-Myers Squibb, Pfizer, Roche; Safety committee member: Oryzon Genomics; Travel support: Boehringer Ingelheim, Pfizer. J. Rodriguez-Cid: Investigational resources: AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Eli Lilly, MSD, Novartis, Roche, Takeda; Advisory role: AbbVie, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Eisai, MSD, Novartis, Pfizer, Roche, Takeda; Speaker role: AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lilly, MSD, Novartis, Pfizer, Roche, Takeda. M. Schenker: For clinical trial participation (as PI/SI) my institution and I have received funds from: AbbVie, Amgen, Astellas, AstraZeneca, Bayer, Bioven, Bristol-Myers Squibb, Eisai, Eli Lilly, Gilead, Merck Serono, MSD, Mylan, Nano Carrier, Novartis, Pfizer, PharmaMar, Regeneron, Roche, Samsung D. Morgensztern: Advisory board: AbbVie, Bristol-Myers Squibb, PharmaMar, Takeda. J. Fairchild: Stock ownership: Bristol-Myers Squibb. C. Baudelet: Employee: Bristol-Myers Squibb. K. Park: Advisor: Bristol-Myers Squibb. All other authors have declared no conflicts of interest.
LBA3 - Efficacy and safety of first-line durvalumab (D) ± tremelimumab (T) vs platinum-based chemotherapy (CT) based on clinical characteristics in patients with metastatic (m) NSCLC: Results from MYSTIC
- B. Cho (Seoul, Korea, Republic of)
- B. Cho (Seoul, Korea, Republic of)
- N. Reinmuth (Gauting, Germany)
- K. Lee (Cheongju, Korea, Republic of)
- M. Ahn (Seoul, Korea, Republic of)
- A. Luft (Saint-Petersburg, Russian Federation)
- M. Van den Heuvel (Amsterdam, Netherlands)
- M. Cobo Dols (Málaga, Spain)
- A. Smolin (Moscow, Russian Federation)
- D. Vicente (Seville, Spain)
- V. Moiseyenko (Saint-Petersburg, Russian Federation)
- S. Antonia (Tampa, FL, United States of America)
- S. Le Moulec (Paris, CEDEX 5, France)
- G. Robinet (Brest, Cedex 2, France)
- R. Natale (Los Angeles, United States of America)
- E. Garon (Santa Monica, CA, United States of America)
- K. Nakagawa (Osaka, Japan)
- F. Liu (Gaithersburg, United States of America)
- P. Thiyagarajah (Cambridge, United Kingdom)
- S. Peters (Lausanne, Switzerland)
- N. Rizvi (New York, United States of America)
Abstract
Background
In MYSTIC (NCT02453282), an open-label, Phase 3 trial of first-line D (anti-PD-L1) ± T (anti-CTLA-4) vs CT in mNSCLC, while not statistically significant, a clinically meaningful improvement in overall survival (OS) was seen with D vs CT in pts with tumour cell PD-L1 expression ≥25% (TC ≥25% [primary analysis population]; D vs CT, HR 0.76 [97.54% CI 0.56–1.02], p=0.036; D+T vs CT, HR 0.85 [98.77% CI 0.61–1.17], p=0.202). Here we report OS in clinically relevant pt subgroups and safety results from MYSTIC.
Methods
Immunotherapy/CT-naïve pts with mNSCLC were randomised (1:1:1) to D (20 mg/kg q4w); D (20 mg/kg q4w) + T (1 mg/kg q4w for 4 cycles); or CT. OS was analysed in pt subgroups based on baseline clinical characteristics in the PD-L1 TC ≥25% population (prespecified: age, gender, race, histology, smoking history and immune cell [IC] PD-L1 expression ≥25% vs <25%; post hoc: ECOG performance status). Safety (CTCAE v4.03) and tolerability were evaluated in all treated pts.
Results
The subgroup analysis included 488 pts (D, 163; D+T, 163; CT, 162). Baseline characteristics were balanced between treatment groups. Treatment with D±T resulted in numerical improvement in OS vs CT in most clinical subgroups. OS in pts aged ≥65 y, PD-L1 IC ≥25%, and performance status 0 showed a HR (95% CI) of 0.66 (0.45, 0.95), 0.63 (0.38, 1.04), and 0.54 (0.34, 0.84), respectively, with D vs CT and a HR (95% CI) of 0.72 (0.50, 1.02), 0.64 (0.39, 1.05), and 0.76 (0.50, 1.14) with D+T vs CT. Rates of TRAEs leading to discontinuation and imAEs were highest with D+T and rates of Grade ≥3 TRAEs were highest with CT (Table). 5 most common events in each category listed in descending order of frequency across the 3 treatment arms. PT, preferred term; TRAE, treatment-related AE; imAE, immune-mediated AE.D (n=369) D+T (n=371) CT (n=352) Any TRAE leading to discontinuation (PT), n (%) 20 (5.4) 49 (13.2) 33 (9.4) →Pneumonitis 3 (0.8) 7 (1.9) 1 (0.3) →Interstitial lung disease 2 (0.5) 5 (1.3) 1 (0.3) →Blood creatinine increased 0 1 (0.3) 4 (1.1) →Colitis 0 5 (1.3) 0 →Diarrhoea 0 4 (1.1) 1 (0.3) Any Grade ≥3 TRAE (PT), n (%) 55 (14.9) 85 (22.9) 119 (33.8) →Anaemia 0 0 36 (10.2) →Neutropenia 1 (0.3) 0 35 (9.9) →Fatigue 6 (1.6) 8 (2.2) 7 (2.0) →Thrombocytopenia 0 0 18 (5.1) →Lipase increased 3 (0.8) 13 (3.5) 1 (0.3) Any imAE (grouped term), n (%) 50 (13.6) 105 (28.3) 12 (3.4) →Hypothyroidism 21 (5.7) 28 (7.5) 2 (0.6) →Pneumonitis 8 (2.2) 25 (6.7) 5 (1.4) →Diarrhoea 7 (1.9) 17 (4.6) 1 (0.3) →Rash 5 (1.4) 16 (4.3) 2 (0.6) →Colitis 2 (0.5) 12 (3.2) 0
Conclusions
In MYSTIC, results of OS analyses across most pt subgroups showed favourable HRs for D±T vs CT, consistent with the overall primary analysis. The safety profile of D±T was manageable and consistent with previous studies with lower rates of Grade ≥3 TRAEs reported compared to CT.
Editorial acknowledgement
Medical writing support, which was in accordance with Good Publication Practice (GPP3) guidelines, was provided by Samantha Holmes, 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
B.C. Cho: Grants/research support: Novartis, AstraZeneca, Yuhan, ONO/BMS, MSD, Bayer; Advisor/honoraria fees: AstraZeneca, Roche, Boehringer Ingelheim, Yuhan, BMS, MSD, Novartis; Speaker’s bureau fees: AZ, BMS, MSD, Novartis. N. Reinmuth: Personal fees: BMS, Roche, AstraZeneca, Takeda, Novartis, Boehringer Ingelheim, MSD, Lilly, outside the conduct of the study. A. Smolin: Grants: AstraZeneca; Grants, personal fees: AstraZeneca, Roche, MSD, BMS; Personal fees: BIOCAD, Boehringer Ingelheim. S.J. Antonia: Advisory boards/contracted research: Novartis; Advisory boards: BMS, Merck, CBMG, Boehringer Ingelheim, AstraZeneca, Memgen, FLX Bio, Nektar, Venn. G. Robinet: Grants, personal fees: AstraZeneca, MSD; Personal fees: Boehringer Ingelheim. R. Natale: Spouse employed (Medical Science Liaison): AstraZeneca - However, her salary and compensation is completely unrelated to the contracted research work performed at my institution for which I am a co-investigator. E.B. Garon: Research funding: Merck, Genentech, AstraZeneca, Novartis, Lilly, BMS, Mirati Therapeutics, Dynavax, Iovance Biotherapeutics. K. Nakagawa: Research funding: GlaxoSmithKline K.K., AstraZeneca K.K., Kyowa Hakko Kirin, Pfizer Japan Inc., AbbVie Inc., Novartis Pharma K.K., Nippon Boehringer Ingelheim, Daiichi Sankyo, Eli Lilly Japan K.K., MSD K.K., Quintiles Inc., Ono Pharmaceutical, BMS, EPS International, Chugai Pharmaceutical, ICON Japan K.K., Gritstone Oncology, Inc., Linical, Yakult Honsha, PAREXEL International Corp., Otsuka Pharmaceutical, Astellas Pharma Inc., AC Medical Inc., Taiho Pharmaceutical, Merck Serono, EPS Associates, Quintiles Inc., Japan Clinical Research Operations, Eisai, PPD-SNBL K.K., Takeda Pharmaceutical, Covance Inc., inVentiv Health Japan, A2 Healthcare Corp., EP-CRSU; Honoraria: Astellas Pharma Inc., AstraZeneca K.K., Novartis Pharma K.K., Pfizer Japan Inc., Chugai Pharmaceutical, Ono Pharmaceutical, Nippon Boehringer Ingelheim, BMS, Kissei Pharmaceutical, Eli Lilly Japan K.K., MSD K.K., EPS Holdings Inc., Showa Yakuhin Kako, Clinical Trial, CareNet, Inc., Nikkei Business Publications, Inc., Nichi-Iko Pharmaceutical, Daiichi Sankyo, Taiho Pharmaceutical, AYUMI Pharmaceutical Corporation, Kyowa Hakko Kirin, Sym Bio Pharmaceuticals, Medicus Shuppan Publishers, Reno Medical K.K., Yodosha, Nanzando; Consulting or advisory role: Astellas Pharma Inc., Eli Lilly Japan K.K., Ono Pharmaceutical, Takeda Pharmaceutical. S. Peters: Personal fees: AbbVie, Amgen, AZ, Bayer, Biocartis, BI, BMS, Clovis, Daiichi Sankyo, Debiopharm, Eli Lilly, F. Hoffmann-La Roche, Foundation Medicine, Illumina, Janssen, MSD, Merck Serono, Merrimack, Novartis, Pharma Mar, Pfizer, Regeneron, Sanofi, Seattle Genetics, Takeda; Non-financial support: Amgen, AZ, BI, BMS, Clovis, F. Hoffmann-La Roche, Illumina, MSD, Merck Serono, Novartis, Pfizer. F. Liu, P. Thiyagarajah: Full-time employment: AstraZeneca. N.A. Rizvi: Advisory boards: AbbVie, AZ, BMS, EMD Serono, Genentech, GSK, Janssen, Lilly, Merck, Novartis, Pfizer, Regeneron, Neogenomics, Oncomed, Gritstone, Bellicum; Equity: Oncomed, Gritstone, Bellicum, ARMO; Royalties: PGDX (patent filed by MSKCC). All other authors have declared no conflicts of interest.
Invited Discussant LBA1_PR and LBA3
- L. Paz-Ares (Madrid, Spain)
- L. Paz-Ares (Madrid, Spain)
102O - Final analysis of the phase III KEYNOTE-042 study: Pembrolizumab (Pembro) versus platinum-based chemotherapy (Chemo) as first-line therapy for patients (Pts) with PD-L1–positive locally advanced/metastatic NSCLC
- T. Mok (Shatin, Hong Kong PRC)
- T. Mok (Shatin, Hong Kong PRC)
- Y. Wu (Guangdong, China)
- I. Kudaba (Riga, Latvia)
- D. Kowalski (Warsaw, Poland)
- B. Cho (Seoul, Korea, Republic of)
- H. Turna (Istanbul, Turkey)
- G. De Castro Jr (São Paulo, Brazil)
- V. Srimuninnimit (Bangkok, Thailand)
- K. Laktionov (Moscow, Russian Federation)
- I. Bondarenko (Dnipro, Ukraine)
- K. Kubota (Tokyo, Japan)
- C. Caglevic (Santiago, Chile)
- B. Karaszewska (Konin, Poland)
- T. Dang (Kenilworth, NJ, United States of America)
- L. Yin (Kenilworth, NJ, United States of America)
- J. Penrod (Kenilworth, NJ, United States of America)
- G. Lopes (Miami, FL, United States of America)
Abstract
Background
Pembro significantly improved OS vs chemo as first-line therapy in pts with PD-L1–positive locally advanced/metastatic NSCLC without EGFR/ALK alterations after median follow-up of 12.8 mo based on interim analysis of KEYNOTE-042 (NCT02220894). We present the final protocol-specified analysis with an additional 6 mo of follow-up.
Methods
Pts were randomized 1:1 to 35 cycles of pembro 200 mg Q3W or chemo (6 cycles of paclitaxel/pemetrexed [pem] + carboplatin with optional pem maintenance [nonsquamous only]), stratified by region (east Asia/non-east Asia), ECOG PS (0/1), histology (squamous/nonsquamous), and PD-L1 tumor proportion score (TPS; ≥50%/1%–49%). No α was allocated to OS in this analysis as the primary hypotheses for OS were met at the interim analysis. PFS differences (secondary endpoints) were assessed sequentially in pts with TPS ≥50%, ≥20%, and ≥1% using the stratified log-rank test (one-sided P = 0.01977, 0.02022, and 0.02065, respectively). Other secondary endpoints were ORR and safety. Duration of response (DOR) was an exploratory endpoint.
Results
1274 pts were randomized, 637 per arm. As of September 4, 2018 (median follow-up, 14 mo), 6% were receiving pembro and 3% were receiving pem maintenance. OS benefit with pembro vs chemo was maintained with longer follow-up (Table). PFS was not significantly improved with pembro vs chemo in pts with TPS ≥50%, therefore secondary efficacy hypotheses were not formally tested beyond TPS ≥50%. DOR was longer with pembro vs chemo (Table). Grade 3–5 treatment-related AEs were less frequent with pembro (18%) vs chemo (41%).
Conclusions
With an additional 6 mo follow-up, pembro demonstrated continued OS benefit vs chemo as first-line therapy in pts with locally advanced/metastatic PD-L1–positive NSCLC without EGFR/ALK alterations.
Clinical trial identification
NCT02220894.
Editorial acknowledgement
Medical writing and editorial assistance was provided by Rozena Varghese, PharmD, of C4 MedSolutions, LLC (Yardley, PA), a CHC Group company. This assistance was funded by 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
T.S.K. Mok: Grants or research support: AstraZeneca, Bristol-Myers Squibb, Clovis Oncology, Merck Sharp & Dohme, Novartis, Pfizer, Roche, SFJ Pharmaceuticals, XCovery; Speakers’ fees: AstraZeneca, Roche/Genentech, Pfizer, Eli Lilly, Boehringer Ingelheim, Merck Sharp & Dohme, Novartis, Bristol-Myers Squibb, Taiho, Takeda Oncology; Honoraria: AstraZeneca, Roche/Genentech, Pfizer, Eli Lilly, Boehringer Ingelheim, Merck Serono, Merck Sharp & Dohme, Novartis, SFJ Pharmaceuticals, ACEA Biosciences, Inc., Vertex Pharmaceuticals, Bristol-Myers Squibb, OncoGenex Pharmaceuticals, Inc., Celgene, Ignyta, Inc., Fishawack Facilitate Ltd, Takeda Oncology, Janssen; Major stockholder: Sanomics Ltd.; Advisory board member: AstraZeneca, Roche/Genentech, Pfizer, Eli Lilly, Boehringer Ingelheim, Clovis Oncology, Merck Serono, Merck Sharp & Dohme, Novartis, SFJ Pharmaceuticals, ACEA Biosciences, Inc., Vertex Pharmaceuticals, Bristol-Myers Squibb, geneDecode Co., Ltd., OncoGenex Technologies Inc., Celgene, Ignyta, Inc., Cirina, Fishawack Facilitate Ltd., Janssen, Takeda, ChiMed. Y-L. Wu: Honoraria: AstraZeneca, Eli Lilly, Roche, Pierre Fabre, Pfizer, Sanofi; Consulting, advisory role: AstraZeneca, Roche, Merck, Boehringer Ingelheim; Research funding to institution: Boehringer Ingelheim, Roche. B.C. Cho: Honoraria: AstraZeneca, Roche, Boehringer Ingelheim; Consultant/advisor: AstraZeneca, Roche, Boehringer Ingelheim; Speakers’ bureau: AstraZeneca, BMS, Merck Sharp & Dohme, Novartis; Research funding: Bayer, AstraZeneca, Yuhan, Novartis. G. de Castro Jr: Consulting, advisory role: AstraZeneca, MSD, BMS, Roche, Novartis, Boehringer Ingelheim; Speakers’ bureau: MSD, BMS, Novartis, AstraZeneca; Travel, accommodation, expenses: MSD, BMS, Roche, Bayer, Novartis, Boehringer Ingelheim, AstraZeneca. K. Kubota: Research funding: Boehringer Ingelheim, Taiho, Ono; Speakers’ fees: Chugai, Taiho, MSD, Boehringer Ingelheim, AstraZeneca, BMS, Eli-Lilly, Daiichi Sankyo, Novartis, Ono, Dainippon-Sumitomo, Kyowa-Kirin, Eisai; Advisory role: Taiho. C. Caglevic: Consultant/advisor: BMS, MSD, Bayer, AZ; Speakers’ bureau: BMS, MSD, Bayer, Lilly, Roche; Research funding: MSD, Boehringer Ingelheim, GSK, Bayer, AZ, Medivation, Astellas Pharma, BMS; Travel, accommodation expenses: Boehringer Ingelheim, MSD. T. Dang, L. Yin, J. Penrod: Employee: Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. G. Lopes: Research funding to institution: Merck & Co., Inc., EMD Serono, AstraZeneca. All other authors have declared no conflicts of interest.
103O_PR - Safety and efficacy of pembrolizumab (Pembro) monotherapy in elderly patients (Pts) with PD-L1–positive advanced NSCLC: Pooled analysis from KEYNOTE-010, -024, and -042
- K. Nosaki (FUKUOKA, Japan)
- K. Nosaki (FUKUOKA, Japan)
- Y. Hosomi (Tokyo, Japan)
- H. Saka (Nagoya, Japan)
- P. Baas (Amsterdam, Netherlands)
- G. De Castro Jr (São Paulo, Brazil)
- M. Reck (Grosshansdorf, Germany)
- Y. Wu (Guangdong, China)
- J. Brahmer (Baltimore, United States of America)
- E. Felip (Barcelona, Spain)
- T. Sawada (Tokyo, Japan)
- K. Noguchi (Tokyo, Japan)
- S. Han (Tokyo, Japan)
- B. Piperdi (Kenilworth, NJ, United States of America)
- D. Kush (Kenilworth, NJ, United States of America)
- G. Lopes (Miami, FL, United States of America)
Abstract
Background
Approximately 70% of newly-diagnosed NSCLC cases occur in the elderly, and more than half are locally advanced/metastatic. We present a pooled analysis of efficacy and safety in elderly pts (aged ≥75 y) enrolled in 3 randomized controlled trials of pembro monotherapy vs standard chemotherapy (chemo) for PD-L1–positive advanced NSCLC.
Methods
Pts were aged ≥18 y with advanced NSCLC with PD-L1 tumor proportion score (TPS) ≥1% (KEYNOTE-010, -042) or TPS ≥50% (KEYNOTE-024). In KEYNOTE-010, pts were randomized to pembro 2 or 10 mg/kg Q3W or docetaxel, as second- or later-line therapy. In KEYNOTE-024 and -042, pts were randomized to first-line pembro 200 mg Q3W or platinum-based chemo. OS was estimated by the Kaplan-Meier method.
Results
The 3 trials included 264 pts aged ≥75 (range, 75–90) y with TPS ≥1%; 132 pts had TPS ≥50%. Independent of line of treatment, HRs (95% CI) for OS favored pembro vs chemo: 0.76 (0.56–1.02) in pts with TPS ≥1% and 0.40 (0.25–0.64) in pts with TPS ≥50%. Pembro also improved OS vs chemo in the pooled analysis of pts with TPS ≥50% who received first-line therapy (KEYNOTE-024 and -042): HR, 0.41 (95% CI, 0.23–0.73). Overall, fewer treatment-related AEs across various categories were observed with pembro vs chemo, in particular, grade 3–5 treatment-related AEs in pts aged ≥75 y (Table). Immune-mediated AEs and infusion reactions were more frequent with pembro vs chemo, with similar frequency in pts receiving pembro aged ≥75 y and <75 y (Table).
Conclusions
In this pooled analysis of pts aged ≥75 y with PD-L1–positive advanced NSCLC, pembro monotherapy improved OS vs chemo, both in pts with PD-L1 TPS ≥1% and PD-L1 TPS ≥50%. The safety profile of pembro was similar in pts aged ≥75 y and <75 y, with lower rates of grade 3–5 treatment-related AEs vs chemo.
Clinical trial identification
NCT01905657 (KEYNOTE-010); NCT02142738 (KEYNOTE-024); NCT02220894 (KEYNOTE-042).
Editorial acknowledgement
Medical writing and editorial assistance was provided by Michael S. McNamara, MS, of C4 MedSolutions, LLC (Yardley, PA), a CHC Group company and funded by 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
K. Nosaki: Honoraria: AstraZeneca, Chugai Pharmaceutical, Eli Lilly, MSD; Institutional research funding: MSD. Y. Hosomi: Personal fees: MSD, AstraZeneca, Eli Lilly Japan, Taiho Pharmaceutical, Chugai Pharmaceutical, Ono Pharmaceutical, Bristol-Myers Squibb. H. Saka: Grants/research support: AstraZeneca, MSD, Ono Pharmaceutical; Honoraria: AstraZeneca, MSD, Ono Pharmaceutical, Chugai Pharmaceutical, Boehringer Ingelheim, Kyorin Pharmaceutical. P. Baas: Consulting role: Genentech/Roche, Merck, Bristol-Myers Squibb, Pfizer; Research support: Bristol-Myers Squibb, Roche, Merck. G. de Castro Jr: Consulting/advisory role: AstraZeneca, MSD, BMS, Roche, Novartis, Boehringer Ingelheim; Speakers’ bureau: MSD, BMS, Novartis, AstraZeneca; Travel/accommodation expenses: MSD, BMS, Roche, Bayer, Novartis, Boehringer Ingelheim, AstraZeneca. M. Reck: Personal fees: Amgen, Hoffmann-La Roche, Lilly, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, MSD, Merck, Novartis, Pfizer, AbbVie. Y-L. Wu: Honoraria: AstraZeneca, Eli Lilly, Roche, Pierre Fabre, Pfizer, Sanofi; Consulting/advisory role: AstraZeneca, Roche, Merck, Boehringer Ingelheim; Research funding to institution: Boehringer Ingelheim, Roche. J.R. Brahmer: Grant, personal fees, Advisory boards, consulting: Merck; Uncompensated advisor and consultant: Bristol-Myers Squibb; Grants: Bristol-Myers Squibb, MedImmune/AstraZeneca; Personal fees: Amgen, Celgene, Lilly. E. Felip: Consulting, advisory role, speaker’s bureau: AbbVie, AstraZeneca, Blueprint Medicines, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Eli Lilly, Guardant Health, Janssen, Merck KGaA, Merck Sharp & Dohme, Novartis, Pfizer, Roche, Takeda; Research funding: Fundación Merck Salud; Grant for Oncology Innovation EMD Serono. T. Sawada, K. Noguchi, S.R. Han: Employee: MSD K.K., Tokyo, Japan. B. Piperdi, D.A. Kush: Employee of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. G. Lopes: Research funding to institution: Merck & Co., Inc., EMD Serono, AstraZeneca.
Invited Discussant 102O and 103O_PR
- S. Popat (London, United Kingdom)
- S. Popat (London, United Kingdom)