LBA56 - Overall survival in the KEYNOTE-671 study of perioperative pembrolizumab for early-stage non-small-cell lung cancer (NSCLC)

Background

At the protocol-specified first interim analysis of the phase 3 KEYNOTE-671 study of resectable early-stage NSCLC (NCT03425643), neoadjuvant pembrolizumab (pembro) + chemotherapy (chemo) followed by resection and adjuvant pembro significantly improved EFS, mPR, and pCR with an expected safety profile vs neoadjuvant chemo and resection alone. We present results of the protocol-specified second interim analysis of KEYNOTE-671.

Methods

Patients (pts) with resectable stage II, IIIA, or IIIB (N2) NSCLC per AJCC v8 were randomized 1:1 to pembro 200 mg (n = 397) or placebo (n = 400) Q3W. Pts were to receive 4 cycles of neoadjuvant pembro or placebo plus cisplatin-based chemo and ≤13 cycles of adjuvant pembro or placebo. Dual primary endpoints are EFS (time from randomization to local progression precluding planned surgery, unresectable tumor, progression or recurrence per RECIST v1.1 by investigator assessment, or death from any cause) and OS.

Results

Median time from randomization to the 10 July 2023 data cutoff was 36.6 mo (range, 18.8-62.0). With 254 (31.9%) deaths, OS was significantly improved in the pembro arm (HR 0.72 [95% CI 0.56-0.93]; P = 0.00517). Median OS was not reached (NR) (95% CI NR-NR) in the pembro arm vs 52.4 mo (95% CI 45.7-NR) in the placebo arm; 36-mo OS rates were 71.3% vs 64.0%. EFS continued to be improved in the pembro arm (HR 0.59 [95% CI 0.48-0.72]; median [95% CI] 47.2 mo [32.9-NR] vs 18.3 mo [14.8-22.1]; 36-mo rate, 54.3% vs 35.4%). Treatment-related AEs were grade ≥3 in 45.2% of pts in the pembro arm vs 37.8% in the placebo arm, led to discontinuation of all treatment in 20.2% vs 9.3%, and led to death in 1.0% vs 0.8% (no new treatment-related deaths since the first interim analysis).

Conclusions

Neoadjuvant pembro + chemo followed by resection and adjuvant pembro provided a statistically significant and clinically important improvement in OS compared with neoadjuvant chemo and resection alone in pts with resectable stage II, IIIA, or IIIB (N2) NSCLC. The OS gains seen in KEYNOTE-671 with the absence of new safety signals establish the perioperative pembro regimen as a new standard of care for resectable early-stage NSCLC.

Clinical trial identification

NCT03425643, first posted February 7, 2018.

Editorial acknowledgement

Editorial assistance provided by Melanie A. Leiby, PhD, an employee of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.

Legal entity responsible for the study

Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.

Funding

Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.

Disclosure

J.D. Spicer: Financial Interests, Personal, Advisory Role, honoraria: AstraZeneca, Merck & Co., Inc., Rahway, NJ, USA, Bristol-Myers Squibb, Amgen, Chemocentryx, Regeneron, Protalix Biotherapeutics, Xenetic Biosciences, Novartis; Financial Interests, Institutional, Funding: AstraZeneca, Merck Sharp & Dohme Corp., Bristol-Myers Squibb, CLS Therapeutics, Protalix Biotherapeutics. S. Gao: Financial Interests, Institutional, Funding, To support study conduct: Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc.. M. Liberman: Financial Interests, Personal, Advisory Board: Johnson & Johnson; Financial Interests, Personal, Stocks/Shares, CMO: Endocision, AssistIQ, Ditch Labs; Financial Interests, Local PI: Merck, AstraZeneca, Pfizer, BMS; Financial Interests, Research Grant: J&J. T. Kato: Financial Interests, Personal, Advisory Board, speaker, consultancy: AstraZeneca, Eli Lilly, Merck Biopharma, MSD; Financial Interests, Personal, Advisory Board, speaker: Pfizer, Amgen, Janssen; Financial Interests, Personal, Other, consultancy: Daiichi Sankyo, Takeda, Taiho; Financial Interests, Personal, Other, consultancy, speaker: Chugai; Financial Interests, Personal, Invited Speaker: Ono, Novartis, Bristol-Meyers Squibb, Boehringer Ingelheim; Financial Interests, Personal, Advisory Board: Beigene, Glaxo; Financial Interests, Personal, Advisory Board, Steering Committee: Roche; Financial Interests, Personal, Full or part-time Employment, Family member: Eli Lilly; Financial Interests, Institutional, Local PI: Chugai, MSD, Pfizer, Eli Lilly, AbbVie, Regeneron, Novartis, Amgen, Merck Biophama, BeiGene, Haihe Biopharma, Blueprint Medicines, Turning Point, Takeda, Daiichi Sankyo, Gilead, GSK, Janssen, Bayer; Financial Interests, Institutional, Steering Committee Member, Local PI: AstraZeneca. M. Tsuboi: Financial Interests, Personal, Invited Speaker, Lecture: Johnson & Johnson Japan; Financial Interests, Personal, Advisory Board, Lectures, Advisory boards: AstraZeneca KK, Chugai Pharmaceutical Co.,Ltd, MSD; Financial Interests, Personal, Invited Speaker, Lectures: Eli Lilly Japan, Bristol-Myers Squibb KK, Taiho Pharma, Medtronic Japan, ONO Pharmaceutical CO.,LTD, Daiichi Sankyo company limited; Financial Interests, Personal, Advisory Board, Advisory boards: Novartis, MiREXS; Financial Interests, Institutional, Research Grant: Beohringer-Ingelheim Japan, MSD, AstraZeneca KK, Ono Pharmaceutical Co.,Ltd, Bristol-Myers Squibb KK, Novartis, MiRXES; Financial Interests, Personal, Steering Committee Member: MSD, AstraZeneca, Novartis; Financial Interests, Institutional, Steering Committee Member: Eli Lilly Japan. S. Lee: Financial Interests, Personal, Advisory Board: AstraZeneca/MedImmune, Roche, Merck, Pfizer, Lilly, BMS/Ono, Takeda, Janssen, IMBdx; Financial Interests, Personal, Invited Speaker: AstraZeneca/MedImmune, Roche, Merck, Lilly, Amgen; Financial Interests, Institutional, Research Grant: Merck, AstraZeneca, Lunit. K. Chen: Financial Interests, Institutional, Funding, Supports study conduct: MSD. M. Majem: Financial Interests, Personal, Advisory Board: Amgen, Roche, AstraZeneca,Takeda, Janssen, Cassen Recordati, BMS; Financial Interests, Personal, Invited Speaker: Amgen, Roche, AstraZeneca, Pfizer, Takeda, Helsinn; Financial Interests, Institutional, Funding: BMS, AstraZeneca, Roche. E. Eigendorff: Financial Interests, Institutional, Funding, Studying funding to the institution to support study conduct: MSD. G. Martinengo: Financial Interests, Institutional, Funding, Funding to institution to suport study conduct: MSD. O. Bylicki: Financial Interests, Personal, Advisory Board, Expert Board: BMS, Roche, Takeda; Financial Interests, Personal, Advisory Board, Annuel contrat: MSD; Financial Interests, Personal, Advisory Board, expert board: AstraZeneca, janssen. M.C. Garassino: Financial Interests, Personal, Advisory Board: Eli Lilly, SeaGen International GmbH, Eli Lilly, Incyte, GSK, Bayer Healthcare Pharmaceuticals, Blueprint Medicines, AstraZeneca UK, AstraZeneca and Daiichi Sankyo Oncology Teams, Roche, Daiichi Sankyo, Mirati Therapeutics, Inc, Daiichi Sankyo/AstraZeneca, AstraZeneca Poland, Daiichi Sankyo, Inc., MSD, Eli Lilly, Pfizer, AstraZeneca/MedImmune, Sanofi Genzyme corporation, Sanofi / Prex, Regeneron Pharmaceuticals, Eli Lilly, Mirati Therapeutics, Inc.; Financial Interests, Personal, Invited Speaker: WebMD, WebMD Oncology/Takeda, MSD Italia, Srl, GrupoPacifico-Secretaria Técnica ICAPEM/AstraZeneca, S.O.S S.r.l, Medscape, ecancer, Ideology; Financial Interests, Personal, Invited Speaker, Global Experts Meeting: AstraZeneca; Financial Interests, Personal, Other, AstraZeneca Spain: Invitation to a lung cancer investigator meeting: AstraZeneca; Financial Interests, Personal, Advisory Board, Advisory Boards: Takeda, Daiichi Sankyo, BeiGene; Financial Interests, Personal, Other, PACIFIC-R Global Scientific Committee: AstraZeneca; Financial Interests, Personal, Other, Steering Committee member and Co-chair at the AstraZeneca Lung Cancer Summit 2019: AstraZeneca; Financial Interests, Personal, Other, MK-3475 KN671 Steering Committee.: MSD; Financial Interests, Personal, Other, Pacific 6 International Coordinating Investigator: AstraZeneca; Financial Interests, Personal, Other, Janssen Scientific Advisory Board and Therapeutic Area Steering Committee Meeting on Lung Cancer: Janssen; Financial Interests, Personal, Other, Pfizer Global Lung Cancer Educational Programme - Steering Committee: Pfizer; Financial Interests, Personal, Other, Seattle Genetics Lung Cancer Platform Study: Seattle Genetics; Financial Interests, Personal, Other, GSK Lung Cancer Global Council: GSK; Financial Interests, Personal, Other, PACIFIC-R Scientific Committee: AstraZeneca UK; Financial Interests, Personal, Other, GSK-Garassino- ZEAL Steering Committee 2020-23: GSK; Financial Interests, Personal, Advisory Board, Advisory Board: AbbVie, Abion, Bayer; Financial Interests, Personal, Invited Speaker, Satellite Symposium: merck; Financial Interests, Personal, Advisory Board, Advisory boards: Merck, Sanofi, Gilead; Financial Interests, Personal, Invited Speaker, Invited speaker: Medscape; Financial Interests, Personal, Advisory Board, Invited speaker: OncoHost; Financial Interests, Personal, Advisory Board, Advisor: Boheringer; Financial Interests, Personal, Steering Committee Member, Member of the MK-3475 KN671 Steering Committee (KEYNOTE-671): MSD; Financial Interests, Personal, Coordinating PI, Coordinating investigator for the MK-3475 KEYNOTE 189: MSD; Financial Interests, Personal and Institutional, Coordinating PI, Pacific 6 Steering Committee and International Coordinating Investigator: AstraZeneca; Financial Interests, Institutional, Steering Committee Member, Steering Committee ML41118 Roche: Roche; Financial Interests, Institutional, Local PI, TURNING POINT: Bayer; Financial Interests, Institutional, Local PI, Phase II: Celgene Corporation, Spectrum Pharmaceuticals, Merk Serono; Financial Interests, Institutional, Local PI, A Phase 1: Janssen; Financial Interests, Institutional, Local PI, Array 818-202: Pfizer; Financial Interests, Institutional, Local PI, PAPILLON Study: Janssen; Financial Interests, Institutional, Local PI: Amgen; Financial Interests, Institutional, Local PI, Phase 3: Bluprint; Financial Interests, Institutional, Local PI, Phase 3 Study RESILIENT: IPSEN Bioscience Inc.; Financial Interests, Institutional, Local PI, Phase III: Amgen, GSK Research & Develpoment Ltd., Novartis; Financial Interests, Institutional, Local PI, Phase III - CEACAM5: Sanofi; Financial Interests, Institutional, Local PI, Phase I-JNJ-61186372, a Human Bispecific EGFR and cMet Antibody: Janssen; Financial Interests, Institutional, Local PI, Phase II - SAVANNAH: AstraZeneca S.p.A.; Financial Interests, Institutional, Local PI, phase III NEOCOAST: MedImmune LCC; Financial Interests, Institutional, Local PI, Phase II - coast: MedImmune LCC; Financial Interests, Institutional, Local PI, Phase III - ADRIATIC: AstraZeneca; Financial Interests, Institutional, Local PI, Phase III (CANOPY-1): Novartis; Financial Interests, Institutional, Local PI, Phase 1b: Exelixis Inc.; Financial Interests, Institutional, Local PI, Phase 3-GO40241: Roche; Financial Interests, Institutional, Local PI, Phase III- CASPIAN: AstraZeneca; Financial Interests, Institutional, Local PI, Phase III CA209-017: BMS; Financial Interests, Institutional, Local PI, MK3475-091 - PEARLS: Merk; Financial Interests, Institutional, Local PI, Phase III - Roche GO29431: Roche; Financial Interests, Institutional, Local PI, Phase III - ARCTIC: AstraZeneca; Financial Interests, Institutional, Local PI, Phase III - AURA 3: AstraZeneca AB; Financial Interests, Institutional, Local PI, Phase III CA209-057: BMS; Financial Interests, Institutional, Local PI, OPEL/2014/14/067: Otsuka Pharmaceutical Italy S.r.l.; Financial Interests, Institutional, Local PI, Phase II - VISION: Merck KGaA; Financial Interests, Institutional, Local PI, Phase III MK-3475-715: Incyte Corporation; Financial Interests, Institutional, Local PI, Phase 1/2 (TRIDENT-1): Turning Point Therapeutics, Inc.; Financial Interests, Institutional, Local PI, HERTHENA-Lung01: A Phase 2: Daiichi Sankyo Development Ltd.; Financial Interests, Institutional, Local PI, Phase II ATLANTIC: AstraZeneca S.p.A.; Financial Interests, Institutional, Local PI, Clinical trial: Affimed; Financial Interests, Institutional, Local PI, Clinical trial poziotinib: spectrum; Non-Financial Interests, Principal Investigator, STYLE Trial: Pfizer; Non-Financial Interests, Principal Investigator, Studio TYME: Eli Lilly; Non-Financial Interests, Principal Investigator, People: MSD; Non-Financial Interests, Principal Investigator, FAME trial: Istituto Nazionale dei Tumori; Non-Financial Interests, Principal Investigator, POST-ALK: Istituto Nazionale dei Tumori; Non-Financial Interests, Principal Investigator, Bando finalizzata Mesotelioma: Istituto Nazionale dei Tumori; Non-Financial Interests, Principal Investigator, TERAVOLT: Istituto Nazionale dei Tumori; Non-Financial Interests, Principal Investigator, IND227: Istituto dei Tumori Pascale - Napoli; Non-Financial Interests, Principal Investigator, Progetto Timoma: Istituto Nazionale dei Tumori; Non-Financial Interests, Principal Investigator, APOLLO: Istituto Nazionale dei Tumori; Non-Financial Interests, Principal Investigator, Beverly: Istituto dei Tumori Pascale - Napoli; Non-Financial Interests, Principal Investigator, RAMES: GOIRC; Non-Financial Interests, Principal Investigator, Studio CHANCE: GOIRC; Non-Financial Interests, Principal Investigator, Creta trial: Sant'Orsola Malpighi - Bologna (Alma Mater Studiorum Università Bologna); Non-Financial Interests, Principal Investigator, MILES 5: Istituto dei Tumori Pascale - Napoli; Non-Financial Interests, Principal Investigator, LIPI: GUSTAVE-ROUSSY PARIGI LIPI TRIAL- no profit; Non-Financial Interests, Principal Investigator: AO Spedali Civili Brescia; Non-Financial Interests, Principal Investigator, phase III trial: European Thoracic Oncology Platform (ETOP); Non-Financial Interests, Leadership Role, Honorary President and Founder: Women for Oncology Italy; Non-Financial Interests, Other, Member of ASCO Scientific Committee (2018-2021): ASCO; Non-Financial Interests, Leadership Role, Board member: AIOT (Associazione Italiana Oncologia Toracica); Non-Financial Interests, Member: AIOM, AIOT; Non-Financial Interests, Member, WCLC annual congress Lung Cancer Track: WCLC; Non-Financial Interests, Member, Scientific Committee: IPOP (Italian lung cancer charity), TUTOR (Italian thymic malignancies charity); Non-Financial Interests, Member, Member since 2013-2018: EMA Scientific Advisory Group (SAG); Non-Financial Interests, Other, Scientific Programme Committee: AACR; Non-Financial Interests, Leadership Role, previous ESMO National Societies Committee Chair and ESMO Council Member: ESMO; Other, Travel, Accommodations, Expenses: Pfizer; Other, Relationships to Disclose Travel, Accommodations, Expenses: Roche, AstraZeneca; Other, travel and accomodation: Merk. D. Rodriguez Abreu: Financial Interests, Personal, Advisory Board: MSD, Novartis, Roche/Genentech, pfizer, Bristol-Myers Squibb, AstraZeneca, Regeneron, Gilead, Sanofi, Amgen, Takeda, Eli Lilly, Incyte, Merck Serono; Financial Interests, Personal, Invited Speaker: MSD, Novartis, Roche/Genentech, pfizer, Bristol-Myers Squibb, AstraZeneca, Regeneron, Gilead, Sanofi, Amgen, Takeda, Eli Lilly, Merck Serono; Financial Interests, Personal, Other, Travel expenses: MSD, Novartis, Roche/Genentech, pfizer. J. Chaft: Other, Personal, Speaker, Consultant, Advisor: arcus biosciences, AstraZeneca, Bristol Myers Squibb Company, Flame biosciences, Guardant Health, Merck, Regeneron Pharmaceuticals; Financial Interests, Institutional, Funding, Funding to support study conduct: Merck Sharp & Dohme; Financial Interests, Institutional, Funding, Funded by Cancer Center Support Grant P30 CA008748: NIH. S. Novello: Financial Interests, Personal, Invited Speaker: AstraZeneca, MSD, Eli Lilly, Novartis, Beigene, Amgen; Financial Interests, Personal, Advisory Board: BI, BMS, Pfizer, Takeda, Roche, Sanofi, Amgen; Financial Interests, Institutional, Coordinating PI, IIT: MSD, BI; Non-Financial Interests, Leadership Role, president of this european advocacy: WALCE. J. Yang: Financial Interests, Personal, Full or part-time Employment: Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc.. S.M. Keller: Financial Interests, Personal, Full or part-time Employment: Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc.; Financial Interests, Personal, Stocks/Shares: Merck & Co., Inc.. A. Samkari: Financial Interests, Personal, Full or part-time Employment: Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc.; Financial Interests, Personal, Stocks/Shares: Merck & Co., Inc.. H. Wakelee: Financial Interests, Personal, Advisory Board, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Blueprint, Mirati; Financial Interests, Personal, Invited Speaker, Develop and present a series of lectures: Fishawack Facilitate LTD; Financial Interests, Personal, Invited Speaker, Series of CME lectures: Medscape, Research to Practice; Financial Interests, Personal, Other, Discussion of new data at conferences: Curio Science; Financial Interests, Personal, Invited Speaker, Series of lectures/webinars for PER/OncLive: MJH Holdings; Financial Interests, Personal, Writing Engagement: UpToDate; Financial Interests, Personal, Invited Speaker, CME lecture: Axis Medical Education, Nexus Oncology; Financial Interests, Institutional, Local PI, Clinical Trial Conduct: ACEA Biosciences, Arrys Therapeutics, AstraZeneca/Medimmune, BMS, Clovis Oncology, Novartis, Seagen, Xcovery; Financial Interests, Institutional, Coordinating PI, Clinical Trial Conduct: Celgene; Financial Interests, Institutional, Steering Committee Member, Clinical Trial Conduct: Genentech/Roche, Merck; Non-Financial Interests, Leadership Role, Executive Committee: ECOG-ACRIN; Financial Interests, Institutional, Local PI, clinical trial conduct: Helsinn; Non-Financial Interests, Officer, President: International Association for the Study of Lung Cancer (IASLC). All other authors have declared no conflicts of interest.