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Displaying One Session

Proffered Paper session
Date
Mon, 20.09.2021
Time
13:30 - 14:50
Location
Channel 1
Proffered Paper session

LBA35 - Avelumab-cetuximab-radiotherapy versus standards of care in patients with locally advanced squamous cell carcinoma of head and neck (LA-SCCHN): Randomized phase III GORTEC-REACH trial

Presentation Number
LBA35
Speakers
  • Jean Bourhis (Lausanne, Switzerland)
Lecture Time
13:30 - 13:40
Location
Channel 1, Paris Expo Porte de Versailles, Paris, France
Date
Mon, 20.09.2021
Time
13:30 - 14:50

Abstract

Background

Based on a potential synergistic effect of anti–PD-L1 avelumab plus cetuximab and radiotherapy (RT), this combination was tested in a randomized phase III trial against 2 standards of care (SOC) in LA-SCCHN.

Methods

The trial comprised 2 cohorts of patients (pts) fit for cisplatin (3 cycles of 100 mg/m2, Q3W) or unfit for cisplatin. The SOC was IMRT 70 Gy / 6.5 weeks with cisplatin in fit pts and with cetuximab in unfit pts (Bonner, 2006). In both cohorts, experimental arm (Exp) was 70 Gy / 6.5 weeks plus weekly cetuximab and avelumab 10 mg/kg at Day-7 and every 2 weeks during RT followed by avelumab for 12 months. The primary endpoint was progression-free survival (PFS). In Unfit pts, 115 events were needed / 277 pts to detect a HR of 0.62 (1-sided 0.05 type I error; power 80%). In Fit pts, 166 events were needed / 430 pts to detect a HR of 0.64 (2-sided 0.05 type I error; power 80%).

Results

Between 2017 and 2020, 707 pts were randomized. For cisplatin unfit pts , out of 277 pts, the number of PFS events was reached. Median age 67 years, 88% smokers, 61% oropharyngeal tumors (35% p16+), 24% stage III, 76% stage IV. Grade >= 3 AEs were 80% in both arms (p=0.91). Median follow-up was 21 months (IQR 15-28). PFS rate at 2 years (95%CI) was 44% (35%-53%) in Exp vs 31% (23%-40%) in Cetux-SOC (HR 0.85; p=0.15). Loco-regional progression at 2 years (95%CI) was 34% (26%-43%) in Exp vs 44% (35%-53%) in Cetux-SOC (HR = 0.83; p=0.34). Distant metastasis rate was lower in Exp (HR = 0.31, p=0.007). The 2-year OS rate (95%CI) was 58% (48%-67%) in Exp vs 54% in SOC (44%-64%) (HR 1.08; p-=0.69). For cisplatin fit pts, out of 430 pts, the number of PFS events was not reached. The interim analysis for futility based on 89 events in 317 first pts showed a 1-year PFS rate (95%CI) of 64% (54%-72%) in Exp vs 73% in SOC-cisplatin (65%-81%): HR 1.27 (95%CI 0.83-1.93), crossing the futility boundary.

Conclusions

In cisplatin-Unfit pts, a favorable effect of adding avelumab to cetuximab was seen on PFS, local-regional control, distant metastases, but the primary endpoint on PFS was not met. In cisplatin-Fit pts, the futility boundary for efficacy was crossed, favoring SOC cisplatin.

Clinical trial identification

NCT02999087.

Legal entity responsible for the study

GORTEC.

Funding

GORTEC with a funding from MERCK Serono. This research was financially supported by Merck Serono S.A.S., Lyon, France, an affiliate of Merck KGaA, as part of an alliance between Merck (CrossRef Funder ID: 10.13039/100009945) and Pfizer.

Disclosure

All authors have declared no conflicts of interest.

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Proffered Paper session

LBA36 - Nivolumab (N) + ipilimumab (I) vs EXTREME as first-line (1L) treatment (tx) for recurrent/metastatic squamous cell carcinoma of the head and neck (R/M SCCHN): Final results of CheckMate 651

Presentation Number
LBA36
Speakers
  • Athanassios Argiris (Marousi, Greece)
Lecture Time
13:40 - 13:50
Location
Channel 1, Paris Expo Porte de Versailles, Paris, France
Date
Mon, 20.09.2021
Time
13:30 - 14:50

Abstract

Background

Despite recent tx advances in R/M SCCHN, durable survival benefit remains an elusive goal. CheckMate 651 (NCT02741570), a phase 3 randomized trial, evaluated N+I vs EXTREME regimen as 1L tx for platinum-eligible R/M SCCHN.

Methods

Pts with R/M SCCHN, no prior systemic therapy in R/M setting, and ECOG PS 0–1 were randomized 1:1 to N (3 mg/kg Q2W) + I (1 mg/kg Q6W; n = 472), or EXTREME (n = 475), stratified by tumor PD-L1 level, p16 expression, and prior chemotherapy. Pts were treated with N+I or EXTREME (cetuximab + cisplatin/carboplatin + fluorouracil ≤6 cycles, then cetuximab maintenance) until progression/unacceptable toxicity, or 2 y for N+I. Primary endpoints were overall survival (OS) in all randomized and PD-L1 combined positive score (CPS) ≥20 populations. OS in CPS ≥1 was a key secondary endpoint. Progression-free survival (PFS), objective response rate (ORR), duration of response (DOR), and safety were also assessed.

Results

947 pts were randomized; baseline characteristics were balanced across arms. At final analysis (minimum follow-up: 27.3 mo), there was no statistically significant improvement in OS with N+I vs EXTREME in all randomized (HR 0.95 [97.9% CI: 0.80–1.13] P = 0.4951) or CPS ≥20 (HR 0.78 [97.5% CI: 0.59–1.03] P = 0.0469) populations. In pts with CPS ≥1, OS HR was 0.82 (95% CI: 0.69–0.97). Other efficacy results are in the table. Overall, 8% (N+I) and 46% (EXTREME) of pts received subsequent immunotherapy. Grade 3/4 tx-related adverse events occurred in 28% vs 71% of treated pts, respectively.

Conclusions

N+I did not show statistically significant OS improvement vs EXTREME in pts with R/M SCCHN; however, there was evidence of clinical activity in pts with CPS ≥20 and CPS ≥1 as shown by prolonged OS (median and 2 y rates) and durable responses. Notably, OS in the control arm was better than historical data. N+I had a favorable safety profile vs EXTREME, with no new safety signals observed.

All randomized CPS ≥20 CPS ≥1
N+I EXTREME N+I EXTREME N+I EXTREME
n 472 475 185 178 355 372
Median OS, mo 95% CI 13.9 12.1–15.8 13.5 12.6–15.2 17.6 13.8–22.0 14.6 12.3–16.0 15.7 13.7–18.8 13.2 11.1–14.6
HR CI 0.95 97.9% CI: 0.80–1.13 0.78 97.5% CI: 0.59–1.03 0.82 95% CI: 0.69–0.97
P value 0.4951 0.0469 -
2-y OS, % 31 28 41 33 34 28
Median PFS, mo95% CI 3.32.8−4.2 6.75.8−7.0 5.43.1–6.9 7.05.6–8.7 4.2 2.9-5.4 6.1 5.6-7.0
HR 95% CI 1.41 1.21−1.65 1.02 0.78–1.33 1.23 1.03−1.47
2-y PFS, % 15 13 26 16 18 13
ORR, n (%) 95% CI 114 (24) 20−28 175 (37) 32−41 63 (34) 27−41 64 (36) 29−44 98 (28) 23-33 133 (36) 31-41
Median DOR, mo 95% CI 16.69.7−29.4 5.95.5−7.0 32.612.1−NR 7.05.7−10.1 18.3 10.9-32.6 6.0 5.6-7.6
18 mo DOR, % 48 20 62 29 52 22

Clinical trial identification

NCT02741570.

Editorial acknowledgement

Writing and editorial assistance was provided by Brooke Middlebrook, CMPP, of Evidence Scientific Solutions, funded by Bristol Myers Squibb.

Legal entity responsible for the study

Bristol Myers Squibb and Ono Pharmaceutical Company Ltd.

Funding

Bristol Myers Squibb (all study sites) and Ono Pharmaceuticals (study sites in Japan, Korea and Taiwan).

Disclosure

A. Argiris: Financial Interests, Personal, Other, Review Committee: AstraZeneca; Financial Interests, Personal, Funding: BMS; Financial Interests, Personal, Invited Speaker: BMS; Financial Interests, Personal, Other, Review Committee: Debiopharm; Financial Interests, Personal, Invited Speaker: Merck Serono; Financial Interests, Personal, Advisory Board: Rakuten Medical, Inc.; Financial Interests, Personal, Funding: Rakuten Medical, Inc. K. Harrington: Financial Interests, Institutional, Advisory Board: Arch Oncology; Financial Interests, Institutional, Advisory Board: AstraZeneca; Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Institutional, Advisory Board: BMS; Financial Interests, Institutional, Invited Speaker: BMS; Financial Interests, Institutional, Advisory Board: Boehringer-Ingelheim; Financial Interests, Institutional, Research Grant: Boehringer-Ingelheim; Financial Interests, Institutional, Advisory Board: Codiak; Financial Interests, Institutional, Advisory Board: Inzen; Financial Interests, Institutional, Advisory Board: Merck-Serono; Financial Interests, Institutional, Invited Speaker: Merck-Serono; Financial Interests, Personal and Institutional, Advisory Board: MSD; Financial Interests, Personal and Institutional, Invited Speaker: MSD; Financial Interests, Personal and Institutional, Research Grant: MSD; Financial Interests, Institutional, Advisory Board: Oncolys; Financial Interests, Institutional, Advisory Board: Pfizer; Financial Interests, Institutional, Advisory Board: PsiVac; Financial Interests, Institutional, Advisory Board: Replimune; Financial Interests, Institutional, Research Grant: Replimune. M. Tahara: Financial Interests, Personal and Institutional, Invited Speaker: Ono Pharmaceutical; Financial Interests, Personal and Institutional, Advisory Board: Ono Pharmaceutical; Financial Interests, Personal and Institutional, Research Grant: Ono Pharmaceutical; Financial Interests, Personal and Institutional, Invited Speaker: BMS; Financial Interests, Personal and Institutional, Advisory Board: BMS; Financial Interests, Personal and Institutional, Research Grant: BMS; Financial Interests, Personal and Institutional, Invited Speaker: MSD; Financial Interests, Personal and Institutional, Advisory Board: MSD; Financial Interests, Personal and Institutional, Research Grant: MSD; Financial Interests, Personal and Institutional, Invited Speaker: Bayer; Financial Interests, Personal and Institutional, Advisory Board: Bayer; Financial Interests, Personal and Institutional, Research Grant: Bayer; Financial Interests, Personal and Institutional, Invited Speaker: Merck Biopharma; Financial Interests, Personal and Institutional, Advisory Board: Merck Biopharma; Financial Interests, Personal and Institutional, Research Grant: Merck Biopharma; Financial Interests, Personal and Institutional, Invited Speaker: Eisai; Financial Interests, Personal and Institutional, Advisory Board: Eisai; Financial Interests, Personal and Institutional, Research Grant: Eisai; Financial Interests, Personal, Advisory Board: LOXO; Financial Interests, Personal, Advisory Board: Celgene; Financial Interests, Personal and Institutional, Invited Speaker: Rakuten Medical; Financial Interests, Personal and Institutional, Advisory Board: Rakuten Medical; Financial Interests, Personal and Institutional, Research Grant: Rakuten Medical; Financial Interests, Personal, Advisory Board: Amgen; Financial Interests, Personal and Institutional, Advisory Board: Novartis; Financial Interests, Personal and Institutional, Research Grant: Novartis. R.L. Ferris: Financial Interests, Personal, Advisory Board: Achilles Therapeutics; Financial Interests, Personal, Advisory Role: Aduro Biotech, Inc; Financial Interests, Institutional, Funding: AstraZeneca/MedImmune; Financial Interests, Personal, Advisory Role: Bicara Therapeutics, Inc; Financial Interests, Personal, Advisory Board: Bristol Myers Squibb; Financial Interests, Institutional, Funding: Bristol Myers Squibb; Financial Interests, Personal, Advisory Board: EMD Serono; Financial Interests, Personal, Advisory Role: Everest Clinical Research Corporation; Financial Interests, Personal, Advisory Role: F. Hoffmann-La Roche Ltd; Financial Interests, Personal, Advisory Role: Genocea Biosciences, Inc; Financial Interests, Personal, Advisory Board: Instil Bio, Inc; Financial Interests, Personal, Advisory Role: Kowa Research Institute, Inc.; Financial Interests, Personal, Advisory Board: Lifescience Dynamics Limited; Financial Interests, Personal, Advisory Board: MacroGenics, Inc.; Financial Interests, Personal, Advisory Board: Merck; Financial Interests, Personal, Advisory Role: Mirati Therapeutics, Inc; Financial Interests, Personal, Advisory Role: Nanobiotix; Financial Interests, Personal, Advisory Role: Novasenta; Financial Interests, Personal, Stocks/Shares: Novasenta; Financial Interests, Institutional, Funding: Novasenta; Financial Interests, Personal, Advisory Board: Numab Therapeutics AG; Financial Interests, Personal, Advisory Board: OncoCyte Corporation; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Role: PPD; Financial Interests, Personal, Advisory Board: Rakuten Medical, Inc; Financial Interests, Personal, Advisory Role: Sanofi; Financial Interests, Personal, Advisory Board: Seagen, Inc; Financial Interests, Institutional, Funding: Tesaro; Financial Interests, Personal, Advisory Role: Zymeworks, Inc. M. Gillison: Financial Interests, Personal and Institutional, Advisory Role: Istari Oncology Inc; Financial Interests, Personal and Institutional, Advisory Role: LLX Solutions, LLC; Financial Interests, Personal and Institutional, Advisory Role: Kura Oncology; Financial Interests, Personal and Institutional, Advisory Role: Mirati Therapeutics; Financial Interests, Personal and Institutional, Advisory Role: BioNtech AG; Financial Interests, Personal and Institutional, Advisory Role: Shattuck Labs, Inc; Financial Interests, Personal and Institutional, Advisory Role: EMD Serono, Inc; Financial Interests, Personal and Institutional, Advisory Role: Depiopharm; Financial Interests, Personal and Institutional, Advisory Role: Merck & Co; Financial Interests, Personal and Institutional, Advisory Role: Ipsen Biopharmaceuticals Inc; Financial Interests, Personal and Institutional, Advisory Role: Gilead Sciences, Inc; Financial Interests, Personal and Institutional, Advisory Role: Bristol Myers Squibb; Financial Interests, Personal and Institutional, Advisory Role: Bicara Therapeutics; Financial Interests, Personal and Institutional, Advisory Role: Bayer Healthcare Pharmaceutics; Financial Interests, Personal and Institutional, Advisory Role: Genocea Biosciences, Inc.; Financial Interests, Personal and Institutional, Invited Speaker: OncLive; Financial Interests, Personal and Institutional, Invited Speaker: Roche; Financial Interests, Personal and Institutional, Advisory Role, Scientific advisory committee: Seagen; Financial Interests, Personal and Institutional, Advisory Role, Scientific advisory committee: Sensei Biotherapeutics, Inc; Financial Interests, Personal and Institutional, Funding, Research funding: Genocea Biosciences, Inc; Financial Interests, Personal and Institutional, Invited Speaker, Research funding: Bristol Myers Squibb; Financial Interests, Personal and Institutional, Invited Speaker, Research funding: Genentech; Financial Interests, Personal and Institutional, Invited Speaker, Research funding: Kura; Financial Interests, Personal and Institutional, Invited Speaker, Research funding: Cullinan Labs; Financial Interests, Personal and Institutional, Other, DSBM: SQZBiotech; Financial Interests, Personal and Institutional, Other, DSBM: BioMimetix. J. Fayette: Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: BMS; Financial Interests, Personal, Advisory Board: Innate Pharma,; Financial Interests, Personal, Advisory Board: Merck Serono,; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Institutional, Other, Research Funding: Seagens; Non-Financial Interests, Personal, Principal Investigator: AstraZeneca . A. Daste: Financial Interests, Personal, Advisory Role, Consulting: Bristol Myers Squibb; Financial Interests, Personal, Advisory Role, Consulting: Merck, Sharp & Dohme; Financial Interests, Personal, Advisory Role, Consulting: Merck. R. Mesia Nin: Financial Interests, Personal, Invited Speaker: Bristol Myers Squibb; Financial Interests, Personal, Invited Speaker: Merck, Sharp & Dohme; Financial Interests, Personal, Invited Speaker: Merck; Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Advisory Board: Bristol Myers Squibb; Financial Interests, Personal, Advisory Board: Merck, Sharp & Dohme; Financial Interests, Personal, Advisory Board: Merck; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Advisory Board: Nanobiotics; Financial Interests, Personal, Advisory Board: Seattle Genetics; Financial Interests, Personal, Advisory Board: Boeringer Ingelheim. N.F. Saba: Financial Interests, Personal, Advisory Board: Merck; Financial Interests, Personal, Advisory Board: Kura; Financial Interests, Personal, Advisory Board: CUE; Financial Interests, Institutional, Funding: Bristol Myers Squibb; Financial Interests, Institutional, Funding: Exelixis; Financial Interests, Personal, Advisory Role: Pfizer . M. Mak: Financial Interests, Personal, Invited Speaker: Bayer; Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Personal, Invited Speaker: Merck Serono; Financial Interests, Personal, Invited Speaker: Takeda; Financial Interests, Personal, Invited Speaker: Amgen. M.A. Álvarez Avitia: Financial Interests, Personal, Invited Speaker: Bristol Myers Squibb; Financial Interests, Personal, Advisory Board: Bristol Myers Squibb; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Invited Speaker: Janssen Mexico; Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Invited Speaker: Merck, Sharp & Dohme; Financial Interests, Personal, Advisory Board: Merck, Sharp & Dohme; Financial Interests, Personal, Invited Speaker: Ipsen. A. Guminski: Financial Interests, Personal, Advisory Board: BMS; Non-Financial Interests, Personal, Other, Conference Travel Support: BMS; Financial Interests, Personal, Advisory Board: Regeneron; Non-Financial Interests, Personal, Principal Investigator: Regeneron; Financial Interests, Personal, Advisory Board: Sanofi; Financial Interests, Personal, Advisory Board: Merck KgA; Non-Financial Interests, Personal, Other, Conference Travel Support: Merck KgA; Non-Financial Interests, Personal and Institutional, Principal Investigator, Investigator Initiated Trial Support: AstraZeneca; Financial Interests, Personal, Advisory Board: MSD; Non-Financial Interests, Personal and Institutional, Research Grant: Sun Pharma; Financial Interests, Personal, Advisory Board: Sun Pharma. U. Müller-Richter: Non-Financial Interests, Personal, Invited Speaker: Bristol Myers Squibb; Non-Financial Interests, Personal, Advisory Board: Bristol Myers Squibb; Non-Financial Interests, Institutional, Funding: Bristol Myers Squibb; Non-Financial Interests, Institutional, Principal Investigator: Bristol Myers Squibb; Non-Financial Interests, Personal, Invited Speaker: Merck, Sharp & Dohme; Non-Financial Interests, Personal, Advisory Board: Merck, Sharp & Dohme; Non-Financial Interests, Personal, Invited Speaker: Merck, Sharp & Dohme; Non-Financial Interests, Personal, Expert Testimony: Merck, Sharp & Dohme; Non-Financial Interests, Institutional, Funding: Merck, Sharp & Dohme; Financial Interests, Institutional, Principal Investigator: Merck, Sharp & Dohme; Non-Financial Interests, Personal, Advisory Board: Sanofi; Non-Financial Interests, Personal, Expert Testimony: Sanofi; Non-Financial Interests, Personal, Writing Engagements: Sanofi; Non-Financial Interests, Institutional, Funding: KuraOncology; Non-Financial Interests, Institutional, Principal Investigator: KuraOncology; Non-Financial Interests, Institutional, Funding: AstraZeneca; Non-Financial Interests, Institutional, Principal Investigator: AstraZeneca; Non-Financial Interests, Institutional, Funding: BioNTech; Non-Financial Interests, Institutional, Principal Investigator: BioNTech. N. Kiyota: Financial Interests, Personal, Speaker’s Bureau, Speaker of sponsored seminar: Bayer; Financial Interests, Personal, Speaker’s Bureau, Speaker of sponsored seminar: Eisai; Financial Interests, Personal, Speaker’s Bureau, Speaker of sponsored seminar: ONO; Financial Interests, Personal, Speaker’s Bureau, Speaker of sponsored seminar: Bristol Myers Squibb; Financial Interests, Personal, Speaker’s Bureau, Speaker of sponsored seminar: Merck, Sharp & Dohme; Financial Interests, Institutional, Research Grant: Adlai Nortye; Financial Interests, Institutional, Research Grant: Bayer; Financial Interests, Institutional, Research Grant: ONO; Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Institutional, Research Grant: Lilly; Financial Interests, Institutional, Research Grant: Bristol Myers Squibb; Financial Interests, Institutional, Research Grant: Rakuten Medical; Financial Interests, Institutional, Advisory Role: Adlai Nortye; Financial Interests, Institutional, Advisory Role: ONO. M. Roberts: Financial Interests, Personal, Full or part-time Employment: BMS; Financial Interests, Personal, Stocks/Shares: BMS . T.A. Khan: Financial Interests, Personal, Full or part-time Employment: BMS; Financial Interests, Personal, Stocks/Shares: BMS. K. Miller-Moslin: Financial Interests, Personal, Full or part-time Employment: Bristol Myers Squibb. L. Wei: Financial Interests, Personal, Full or part-time Employment: BMS. R. Robert Haddad: Financial Interests, Personal, Full or part-time Employment: Dana-Farber Cancer Institute; Financial Interests, Personal, Leadership Role: National Comprehensive Cancer Network; Financial Interests, Personal, Advisory Role: Celgene; Financial Interests, Personal, Advisory Role: Merck; Financial Interests, Personal, Advisory Role: Eisai; Financial Interests, Personal, Advisory Role: Bristol Myers Squibb; Financial Interests, Personal, Advisory Role: AstraZeneca; Financial Interests, Personal, Advisory Role: Pfizer; Financial Interests, Personal, Advisory Role: Loxo; Financial Interests, Personal, Advisory Role: Genentech; Financial Interests, Personal, Advisory Role: Immunomic Therapeutics; Financial Interests, Personal, Advisory Role: GSK; Financial Interests, Personal, Advisory Role: Gilead Sciences; Financial Interests, Personal, Advisory Role: Vaccinex; Financial Interests, Personal, Advisory Role: EMD Serono; Financial Interests, Personal, Advisory Role: BioNTech AG; Financial Interests, Personal, Advisory Role: Achilles Therapeutics; Financial Interests, Personal, Advisory Role: Bayer; Financial Interests, Personal, Advisory Role: Mirati Therapeutics; Financial Interests, Institutional, Funding, Research Funding: Boehringer Ingelheim; Financial Interests, Institutional, Funding, Research Funding: Merck; Financial Interests, Institutional, Funding, Research funding: Bristol Myers Squibb; Financial Interests, Institutional, Funding, Research funding: Celgene; Financial Interests, Institutional, Funding, Research funding: AstraZeneca; Financial Interests, Institutional, Funding, Research Funding: VentiRx; Financial Interests, Institutional, Funding, Research Funding: Genentech; Financial Interests, Institutional, Funding, Research Funding: Pfizer; Financial Interests, Institutional, Funding, Research Funding: Kura; Financial Interests, Personal, Other: Nanobiotix; Financial Interests, Personal, Other: ISA Pharmaceuticals; Financial Interests, Personal, Other, Patents, Royalties, Other Intellectual Property: UpToDate. All other authors have declared no conflicts of interest.

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Proffered Paper session

Invited Discussant LBA35 and LBA36

Speakers
  • Amanda Psyrri (Haidari, Greece)
Lecture Time
13:50 - 14:00
Location
Channel 1, Paris Expo Porte de Versailles, Paris, France
Date
Mon, 20.09.2021
Time
13:30 - 14:50
Proffered Paper session

Q&A and live discussion

Speakers
  • Amanda Psyrri (Haidari, Greece)
Lecture Time
14:00 - 14:10
Location
Channel 1, Paris Expo Porte de Versailles, Paris, France
Date
Mon, 20.09.2021
Time
13:30 - 14:50
Proffered Paper session

858O - Results of KEYNOTE-122: A phase III study of pembrolizumab (pembro) monotherapy vs chemotherapy (chemo) for platinum-pretreated, recurrent or metastatic (R/M) nasopharyngeal carcinoma (NPC)

Presentation Number
858O
Speakers
  • Anthony T.C. T. Chan (Sha Tin, Hong Kong PRC)
Lecture Time
14:10 - 14:20
Location
Channel 1, Paris Expo Porte de Versailles, Paris, France
Date
Mon, 20.09.2021
Time
13:30 - 14:50

Abstract

Background

Treatment options for R/M NPC are limited. In the phase Ib KEYNOTE-028 trial, pembro showed antitumor activity and manageable safety in a cohort of 27 patients (pts) with R/M NPC. KEYNOTE-122 (NCT02611960) is a multicenter, open-label, randomized phase III study to evaluate the efficacy and safety of pembro monotherapy vs chemo in pts with platinum-pretreated, R/M NPC.

Methods

Pts with histologically confirmed non-keratinizing differentiated (WHO Class II) or undifferentiated (WHO Class III), platinum-pretreated, Epstein-Barr Virus positive R/M NPC, ECOG PS 0-1, and measurable disease per RECIST v1.1 were randomized 1:1 to pembro 200 mg Q3W for up to 35 cycles or investigator’s choice of standard doses of chemo (capecitabine [C], gemcitabine [G], or docetaxel [D]). Primary endpoint was OS (overall significance threshold: 0.025, one-sided). Secondary endpoints included PFS, ORR, and DOR (all per RECIST v1.1 by BICR).

Results

Between May 5, 2016 and May 28, 2018, 233 pts were randomized to pembro (N=117) or chemo (N=116; C: n=39; G, n=46; D, n=31). 74.4% pts in the pembro arm and 62.9% in the chemo arm had PD-L1 CPS≥1. Median time from the first dose to data cutoff (Nov 30, 2020) was 45.1 (range, 30.2-54.8) mo. In the ITT population, median OS was 17.2 months (95% CI, 11.7–22.9) with pembro and 15.3 months (10.9–18.1) with chemo (HR, 0.90; 95% CI, 0.67-1.19; P=0.2262; significance threshold for final analysis: 0.0187); OS rate at 24 months was 40.2% with pembro vs 32.2% with chemo. Other key efficacy outcomes are summarized in the table. Biomarker analyses are ongoing. Treatment-related AEs incidence was 61.2% with pembro and 87.5% with chemo (grade 3-5, 10.3% vs 43.8%).

Conclusions

Pembro monotherapy did not improve OS vs chemo in pts with platinum-pretreated R/M NPC. PD-L1 CPS ≥1 did not enrich for OS or ORR for pembro. Pembro showed manageable safety and a lower incidence of treatment-related AEs vs chemo.

ITT population Pembro Chemo
N=117 N=116
OS, median (95% CI), mo 17.2 (11.7–22.9) 15.3 (10.9–18.1)
HR (95% CI) 0.90 (0.67-1.19); P=0.2262
PFS, median (95% CI), mo 4.1 (2.1-5.6) 5.5 (4.0-8.1)
HR (95% CI) 1.28 (0.94-1.75)
ORR, % (95% CI) 21.4 (14.3-29.9) 23.3 (15.9-32.0)
DCR (CR+PR+SD), % (95% CI) 50.4 (41.0-59.8) 63.8 (54.4-72.5)
DOR, median (range), mo 12.0 (1.7+-49.7+) 13.1 (2.6-49.3+)
Patients with PD-L1 CPS≥1 n=87 n=73
OS, median (95% CI), mo 17.2 (10.0-27.0) 18.0 (12.1-23.9)
ORR, % (95% CI) 23.0 (14.6-33.2) 26.0 (16.5-37.6)

Clinical trial identification

NCT02611960.

Editorial acknowledgement

Medical writing assistance was provided by Yue Liu 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

A.T.C.T.C. Chan: Financial Interests, Institutional, Research Grant: Merck Serono, Merck Sharp & Dohme, Novartis, Pfizer, Eli Lilly, ; Financial Interests, Institutional, Funding: Merck Sharp & Dohme; Financial Interests, Personal, Advisory Role: Merck Sharp & Dohme, Merck Serono, Cullinan Management Inc., Beigene, Springer, Pfizer, ; Financial Interests, Personal, Other, Travel: Bristol Myers Squibb, Merck Sharp & Dohme, Pfizer, Roche, Novartis, AstraZeneca; Financial Interests, Personal, Advisory Board: Merck Sharp & Dohme, Tessa Therapeutics Ltd; Non-Financial Interests, Personal, Other: Immunomic Therpeutics, Inc Angene Biotechnology, Owlstone Medical Limited. V.H.F. Lee: Financial Interests, Institutional, Funding: Merck Sharp & Dohme; Financial Interests, Personal, Research Grant: Merck Sharp & Dohme; Financial Interests, Personal, Advisory Role: Merck Sharp & Dohme. R. Hong: Financial Interests, Institutional, Funding: Merck Sharp & Dohme; Financial Interests, Institutional, Research Grant: Merck Sharp & Dohme. M. Ahn: Financial Interests, Personal, Other, Honoraria: AstraZeneca, Takeda, Merck Sharp & Dohme, Ono, Bristol Myers Squibb, Lilly, Amgen, Merck, Roche; Financial Interests, Personal, Advisory Role: AstraZeneca, Takeda, Merck Sharp & Dohme, Ono, Bristol Myers Squibb, Lilly, Amgen, Merck, Roche, Alpha Pharmaceuticals; Financial Interests, Personal, Research Grant: AstraZeneca, Roche, Merck Sharp & Dohme. W.Q. Chong: Financial Interests, Institutional, Funding: Merck Sharp & Dohme; Financial Interests, Personal, Other, Travel payment: Merck Sharp & Dohme, Amgen. S. Kim: Financial Interests, Institutional, Funding: Merck Sharp & Dohme; Financial Interests, Institutional, Research Grant: Novartis, Sanofi Aventis, Dongkook Pharm Co; Financial Interests, Personal, Advisory Role: Novartis, AstraZeneca, Lilly, DaeHwa Pharma Co.,Ltd, ISU Abix, Daiichi-Sankyo; Financial Interests, Personal, Stocks/Shares: Genopeaks, Neogene TC. H. Gwo Fuang: Financial Interests, Institutional, Research Grant: Merck Sharp & Dohme, AstraZenenca, Eli Lily, Arcus Biosciences, Inc., Pfizer, INEX EpiTherapeutics Pte. Ltd., Roche, Astella, Novartis, Tessa Therapeutics, Regeneron, Samsung Bioepis; Financial Interests, Personal, Invited Speaker: Eli Lily, Merck, Pfizer; Financial Interests, Personal, Other, Travel Expenses: AstraZenenca, Bristol-Myers Squibb Pte Ltd; Financial Interests, Personal, Advisory Board: Pfizer, Boehringer ingelheim, AstraZenenca, MIMS, Merck Sharp & Dohme, Eli Lily. P.B. Caguioa: Financial Interests, Personal, Other, honoraria: Roche, AstraZeneca, Novartis, Merck Sharp & Dohme; Financial Interests, Institutional, Funding: Merck Sharp & Dohme. N. Ngamphaiboon: Financial Interests, Institutional, Research Grant: Merck Sharp & Dohme, Roche, Exelixis, RAPT therapeutics, BeiGene, Pfizer; Financial Interests, Personal, Other, Honoraria: Roche, AstraZeneca, Amgen, Merck Sharp & Dohme, Taiho; Financial Interests, Personal, Advisory Board: Merck Sharp & Dohme, Amgen, Novartis, Bayer, AstraZeneca, Claris, Elli-Lilly. C. Ho: Financial Interests, Institutional, Funding: Merck Sharp & Dohme; Financial Interests, Personal, Research Grant: AstraZeneca , Roche; Financial Interests, Personal, Other, Honoraria: AstraZeneca, Bristol Myers Squibb, Boehringer Ingelheim, Bayer, Eisai, EMD Serono, Merck, Novartis, Roche; Financial Interests, Personal, Other, Travel Payments: Roche. M.A.S. Abdul Aziz: Financial Interests, Institutional, Funding: Merck Sharp & Dohme. Q.S. Ng: Financial Interests, Institutional, Funding: Merck Sharp & Dohme; Financial Interests, Personal, Other, Travel: Merck Sharp & Dohme; Financial Interests, Personal, Advisory Board: Merck Sharp & Dohme. C. Yen: Financial Interests, Institutional, Funding: Merck Sharp & Dohme. N. Soparattanapaisarn: Financial Interests, Institutional, Funding: Merck Sharp & Dohme; Financial Interests, Personal, Research Grant: Merck Sharp & Dohme ; Financial Interests, Personal, Research Grant: AstraZeneca ; Financial Interests, Personal, Research Grant: Roche ; Financial Interests, Personal, Research Grant: Bristol Myers Squibb. K.C.R. Ngan: Financial Interests, Institutional, Funding: Merck Sharp & Dohme; Financial Interests, Personal, Advisory Role: Pfizer, Novartis, Sanofi, AstraZeneca, Lilly, Merck Sharp & Dohme, Zai Lab, Roche, Eisai; Financial Interests, Personal, Other, Honoraria: Novartis, AstraZeneca, Sanofi, Pfizer, Zai Lab, Eisai, Lilly, Merck Sharp & Dohme; Financial Interests, Personal, Other, Travel payments: Pfizer, Astellas, Novartis, Merck Sharp & Dohme, Roche, Esiai, Merck, Sanofi, Bristol Myers Squibb, Zai Lab; Financial Interests, Personal, Advisory Board: Nuance Biotech (Shenzhen, China); Financial Interests, Personal, Leadership Role: President, Hong Kong Breast Oncology Group. S.K. Kho: Financial Interests, Institutional, Funding: Merck Sharp & Dohme. R. Swaby: Financial Interests, Personal, Full or part-time Employment: Merck & Co., Inc.; Financial Interests, Personal, Stocks/Shares: Merck & Co., Inc. S. Saraf: Financial Interests, Personal, Full or part-time Employment: Merck & Co., Inc.; Financial Interests, Personal, Stocks/Shares: Merck & Co., Inc. J. Ge: Financial Interests, Personal, Full or part-time Employment: Merck & Co., Inc.; Financial Interests, Personal, Stocks/Shares: Merck & Co., Inc. L.L. Siu: Financial Interests, Institutional, Funding: Merck Sharp & Dohme; Financial Interests, Personal, Advisory Board: Merck Sharp & Dohme; Financial Interests, Institutional, Funding: Novartis; Financial Interests, Institutional, Funding: Bristol Myers Squibb; Financial Interests, Institutional, Funding: Pfizer; Financial Interests, Institutional, Funding: Boerhinger-Ingelheim; Financial Interests, Institutional, Funding: GlaxoSmithKline; Financial Interests, Institutional, Funding: Roche/Genentech; Financial Interests, Institutional, Funding: Karyopharm; Financial Interests, Institutional, Funding: AstraZeneca; Financial Interests, Institutional, Funding: Astellas; Financial Interests, Institutional, Funding: Bayer; Financial Interests, Institutional, Funding: Abbvie; Financial Interests, Institutional, Funding: Amgen; Financial Interests, Institutional, Funding: Symphogen; Financial Interests, Institutional, Funding: Intensity Therapeutics; Financial Interests, Institutional, Funding: Mirati; Financial Interests, Institutional, Funding: Shattucks; Financial Interests, Institutional, Funding: Avid; Financial Interests, Personal, Advisory Role: Pfizer; Financial Interests, Personal, Advisory Role: Celgene; Financial Interests, Personal, Advisory Role: Morphosys; Financial Interests, Personal, Advisory Role: Roche; Financial Interests, Personal, Advisory Role: Oncorus; Financial Interests, Personal, Advisory Role: Symphogen; Financial Interests, Personal, Advisory Role: Seattle Genetics; Financial Interests, Personal, Advisory Role: GlaxoSmithKline; Financial Interests, Personal, Advisory Role: Voronoi; Financial Interests, Personal, Advisory Role: Treadwell Therapeutics; Financial Interests, Personal, Advisory Role: Arvinas; Financial Interests, Personal, Advisory Role: Tessa; Financial Interests, Personal, Advisory Role: Navire; Financial Interests, Personal, Advisory Role: Relay; Financial Interests, Personal, Advisory Role: Rubius; Financial Interests, Personal, Advisory Role: Daiichi Sankyo; Financial Interests, Personal, Advisory Role: Janpix.

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Proffered Paper session

859O - Refining TNM staging system for Epstein-Barr virus-related nasopharyngeal carcinoma: A multicenter cohort study

Presentation Number
859O
Speakers
  • Wang-Zhong Li (Guangzhou, China)
Lecture Time
14:20 - 14:30
Location
Channel 1, Paris Expo Porte de Versailles, Paris, France
Date
Mon, 20.09.2021
Time
13:30 - 14:50

Abstract

Background

Additional nonanatomic prognostic factors beyond TNM categories supplement evidence-based TNM classifications. We aimed to refine TNM staging groups for Epstein-Barr virus (EBV)-related nasopharyngeal carcinoma (NPC) by incorporating the EBV DNA status.

Methods

This multicenter retrospective cohort comprised 2,354 patients with nonmetastatic NPC treated with radiotherapy with or without chemotherapy between January 2008 and December 2016. Progression-free survival (PFS) and overall survival (OS) according to EBV DNA status and the 8th edition TNM staging system were compared. Recursive partitioning analysis (RPA) combined with supervised clustering was applied to derive prognostic groupings. A refined RPA stage was developed, validated, and compared with existing staging schemes.

Results

Pretreatment EBV DNA status was an independent prognostic factor. Lower survival probability by higher TNM stage was evident in EBV DNA (+) patients but not in those with EBV DNA (-) disease. Integrating EBV DNA status and TNM stage, the RPA stage divided nonmetastatic NPC into RPA-I (T1-3N0 or EBV DNA [-] T1-3N1), RPA-II (EBV DNA [+] T1-3N1-2 or EBV DNA [-] T1-3N2-3/T4N0-3), and RPA-III (EBV DNA [+] T4N0-3/T1-3N3) with distinctly different prognosis. The RPA stage outperformed the current TNM stage and two reported RPA staging schemes. These results were internally and externally validated. The new staging system identified approximately two-fold low-risk patients that might not benefit from chemotherapy than the current TNM staging system.

Conclusions

We developed and validated an RPA-based staging system for EBV-related NPC. This staging system may facilitate prognostic stratification and clinical trial designs.

Legal entity responsible for the study

The authors.

Funding

National Natural Science Foundation of China; Guangdong Medical Research Foundation; Young Teacher Training Project of Sun Yat-sen University.

Disclosure

All authors have declared no conflicts of interest.

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Proffered Paper session

Invited Discussant 858O and 859O

Speakers
  • Lisa F. Licitra (Milan, Italy)
Lecture Time
14:30 - 14:40
Location
Channel 1, Paris Expo Porte de Versailles, Paris, France
Date
Mon, 20.09.2021
Time
13:30 - 14:50
Proffered Paper session

Q&A and live discussion

Speakers
  • Lisa F. Licitra (Milan, Italy)
Lecture Time
14:40 - 14:50
Location
Channel 1, Paris Expo Porte de Versailles, Paris, France
Date
Mon, 20.09.2021
Time
13:30 - 14:50