LBA3 - Perioperative Pembrolizumab (pembro) Plus Neoadjuvant Chemotherapy (chemo) in Early-Stage Non-Small-Cell Lung Cancer (NSCLC): A 4-Year Update of KEYNOTE-671

Background

In the phase 3 KEYNOTE-671 study, perioperative pembro significantly improved EFS (HR, 0.58; 95% CI, 0.46–0.72; P < 0.001) and OS (HR, 0.72; 95% CI, 0.56–0.93; P = 0.0052) vs neoadjuvant chemo and surgery alone and showed manageable safety in patients (pts) with early stage NSCLC. We report results after ⁓4 years of follow-up from KEYNOTE-671.

Methods

Pts (≥18 years) with untreated resectable stage II, IIIA, or IIIB (N2) NSCLC were randomized 1:1 to pembro 200 mg or placebo Q3W plus chemo for 4 cycles followed by surgery then adjuvant pembro 200 mg or placebo Q3W for up to 13 cycles (∼9 mo). Randomization was stratified by disease stage (II vs III), PD-L1 tumor proportion score (<50% vs ≥50%), tumor histology (squamous vs nonsquamous), and geographic region (East Asia vs not East Asia). Dual primary endpoints were EFS per RECIST v1.1 by investigator assessment and OS; secondary endpoints included safety.

Results

797 pts were randomized to the pembro (n = 397) or placebo (n = 400) arms. Median time from randomization to data cutoff (August 19, 2024) was 41.1 (range, 0.4–75.3) mo. The HR for EFS was 0.57 (95% CI, 0.47–0.69) and OS HR was 0.73 (95% CI, 0.58–0.92; Table). Grade ≥3 treatment-related AEs occurred in 179/396 pts (45.2%) in the pembro arm and 151/399 pts (37.8%) in the placebo arm; 4 (1.0%) and 3 (0.8%) treatment-related deaths occurred, respectively. Immune-mediated AEs and infusion reactions occurred in 103 pts (26.0%) in the pembro arm and 37 pts (9.3%) in the placebo arm, with 25 (6.3%) and 7 (1.8%), respectively, as grade ≥3. Table: LBA3

Conclusions

The clinically meaningful EFS and OS benefit of adding perioperative pembro to neoadjuvant chemo in pts with early-stage NSCLC is maintained over ⁓4 years of follow-up, supporting this regimen as a standard of care treatment option for this population.

Clinical trial identification

NCT03425643; EudraCT 2017-001832-21.

Editorial acknowledgement

Medical writing assistance was provided by Aisling Towell, PhD, of ICON plc (Dublin, Ireland). This assistance was funded by 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

M. Majem: Financial Interests, Personal, Advisory Board: Amgen; Financial Interests, Personal, Invited Speaker: Amgen; Financial Interests, Personal, Advisory Board: ROCHE; Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Personal, Advisory Board: Takeda; Financial Interests, Personal, Invited Speaker: Takeda; Financial Interests, Personal, Advisory Board: Janssen; Financial Interests, Personal, Advisory Board: Cassen Recordati; Financial Interests, Personal, Invited Speaker: Helsinn; Financial Interests, Personal, Advisory Board: Bms; Financial Interests, Personal, Advisory Board: Sanofi; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Invited Speaker: Cassen Recordatti; Financial Interests, Institutional, Funding: BMS; Financial Interests, Institutional, Funding: AstraZeneca; Financial Interests, Institutional, Funding: Roche; Non-Financial Interests, Personal, Leadership Role, Board Member: Associacio Contra El Cancer Barcelona; Non-Financial Interests, Personal, Leadership Role: Asocacion Para La Investigacion Del Cancer De Pulmon En Mujeres. M.C. Garassino: Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Abion; Financial Interests, Personal, Advisory Board: MSD International GmbH; Financial Interests, Personal, Advisory Board: BMS; Financial Interests, Personal, Advisory Board: Boehringer Ingelheim Italia S.p.A; Financial Interests, Personal, Advisory Board: Celgene; Financial Interests, Personal, Advisory Board: Eli Lilly; Financial Interests, Personal, Advisory Board: Incyte; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Advisory Board: Takeda; Financial Interests, Personal, Advisory Board: Seattle Genetics; Financial Interests, Personal, Advisory Board: Mirati; Financial Interests, Personal, Advisory Board: Daiichi Sankyo; Financial Interests, Personal, Advisory Board: Regeneron; Financial Interests, Personal, Advisory Board: Merck & Co., Inc., Rahway, NJ, USA; Financial Interests, Personal, Advisory Board: Blueprint; Financial Interests, Personal, Advisory Board: Janssen; Financial Interests, Personal, Advisory Board: Sanofi; Financial Interests, Personal, Advisory Board: AbbVie; Financial Interests, Personal, Advisory Board: BeiGene; Financial Interests, Personal, Advisory Board: Oncohost; Financial Interests, Personal, Advisory Board: Medscape, Financial Interests, Personal, Advisory Board: Gilead; Financial Interests, Personal, Advisory Board: lo Biotech; Financial Interests, Personal, Advisory Board: Revolution Medicines; Financial Interests, Institutional, Invited Speaker: AstraZeneca; Financial Interests, Institutional, Invited Speaker: Merck & Co., Inc., Rahway, NJ, USA; Financial Interests, Institutional, Invited Speaker: Daiichi Sankyo; Financial Interests, Institutional, Invited Speaker: Gilead; Financial Interests, Institutional, Invited Speaker: Eli Lilly; Financial Interests, Institutional, Invited Speaker: Regeneron; Financial Interests, Personal, Advisory Role: AstraZeneca. B. Mennecier: Speaker fees from Amgen, AstraZeneca, Pfizer, Roche, Novartis, Pierre Fabre, BMS, MSD and Takeda; Advisory Board fees from Amgen, AstraZeneca, BMS, Janssen, Pfizer, Pierre Fabre, Sanofi, Novocure and Takeda; and has received support for attending meetings and/or travel from Daiichi Sankyo, MSD, BMS, AstraZeneca. N. Ikeda: Financial Interests, Personal, Funding: AstraZeneca; Financial Interests, Personal, Funding: Chugai Pharma; Financial Interests, Personal, Funding: Boehringer Ingelheim; Financial Interests, Personal, Funding: Taiho Pharma; Financial Interests, Personal, Funding: Eli Lilly; Financial Interests, Personal, Funding: Ono Pharma; Financial Interests, Personal, Funding: BMS; Financial Interests, Personal, Funding: MSD; Financial Interests, Personal, Funding: Nihon Mediphysics; Financial Interests, Personal, Funding: Teijin Pharma; Financial Interests, Personal, Funding: Eisai; Financial Interests, Personal, Funding: Daiichi-Sankyo; Financial Interests, Personal, Funding: Fuji film; Financial Interests, Personal, Funding:, Johnson & Johnson; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Chugai Pharma; Financial Interests, Personal, Advisory Board: Boehringer Ingelheim; Financial Interests, Personal, Advisory Board: Taiho Pharma; Financial Interests, Personal, Advisory Board: Eli Lilly; Financial Interests, Personal, Advisory Board: Ono Pharma; Financial Interests, Personal, Advisory Board: BMS; Financial Interests, Personal, Advisory Board: Olympus; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Advisory Board: Johnson & Johnson; Financial Interests, Personal, Advisory Board: Nihon Mediphysics; Financial Interests, Personal, Advisory Board: Medtronics; Financial Interests, Personal, Advisory Board: Teijin Pharma; Financial Interests, Personal, Leadership Role: Japan Surgical Society ; Financial Interests, Personal, Leadership Role: Japan Lung Cancer Society. J. Bosch-Barrera: Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Personal, Invited Speaker: BMS; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Advisory Board: Sanofi; Other, Personal, Other, Relative (sister in law) working for this company: AstraZeneca. Y. Lou: Financial Interests, Personal, Funding: MSD; Financial Interests, Personal, Funding: Tolero Pharmaceuticals; Financial Interests, Personal, Funding: AstraZeneca; Financial Interests, Personal, Funding: Blueprint Medicines; Financial Interests, Personal, Funding: Sun Pharma; Financial Interests, Personal, Funding: Mirati Therapeutics; Financial Interests, Personal, Funding: Genmab; Financial Interests, Personal, Funding: EMD Serono; Financial Interests, Personal, Funding: Jacobio pharma; Financial Interests, Personal, Funding: Topallian; Financial Interests, Personal, Funding: Daiichi Sankyo; Financial Interests, Personal, Funding: Verastem; Financial Interests, Personal, Funding: Rayze Bio; Financial Interests, Personal, Funding: A2 Biotherapeutics; Financial Interests, Personal, Funding: Elephas; Financial Interests, Personal, Funding: Pyrotech Therapeutics; Financial Interests, Personal, Funding: Novartis; Financial Interests, Personal, Funding: Oric. D. Das: Financial Interests, Personal, Full or part-time Employment: Merck Sharp & Dohme LLC. S.M. Keller: Financial Interests, Personal, Full or part-time Employment: Merck Sharp & Dohme LLC; Financial Interests, Personal, Stocks/Shares: Merck Sharp & Dohme LLC. A. Samkari: Financial Interests, Personal, Full or part-time Employment: Merck Sharp & Dohme LLC; Financial Interests, Personal, Stocks/Shares: Merck Sharp & Dohme LLC. J. Spicer: Financial Interests, Personal, Funding: AstraZeneca; Financial Interests, Personal, Funding: MSD; Financial Interests, Personal, Funding: Roche; Financial Interests, Personal, Funding: BMS; Financial Interests, Personal, Funding: CLS Therapeutics; Financial Interests, Personal, Funding: Protalix Biotherapeutics; Financial Interests, Personal, Funding: Pfizer; Financial Interests, Personal, Funding: Regeneron; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Merck; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Advisory Board: BMS; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: Chemocentryx; Financial Interests, Personal, Advisory Board: Amgen; Financial Interests, Personal, Advisory Board: Protalix Biotherapeutics; Financial Interests, Personal, Advisory Board: Xenetic Biosciences; Financial Interests, Personal, Advisory Board: Regeneron, Eisai; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Invited Speaker: Peerview; Financial Interests, Personal, Invited Speaker: OncLive,; Financial Interests, Personal, Invited Speaker: Medscape; Financial Interests, Personal, Speaker, Consultant, Advisor: AstraZeneca; Financial Interests, Personal, Speaker, Consultant, Advisor: Merck; Financial Interests, Personal, Speaker, Consultant, Advisor: BMS; Financial Interests, Personal, Coordinating PI: AstraZeneca; Financial Interests, Personal, Research Grant: Roche; Financial Interests, Personal, Research Grant: MSD; Financial Interests, Personal, Research Grant: BMS; Financial Interests, Personal, Research Grant: AstraZeneca. H. Wakelee: Financial Interests, Personal, Advisory Board, Served on a DSMC, completed November 2022: 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; Financial Interests, Personal, Invited Speaker, Series of CME lectures: 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, Invited Speaker, CME lecture: Axis Medical Education; Financial Interests, Personal, Advisory Board: IOBiotech; Financial Interests, Personal, Invited Speaker, Facilitated speaking at several virtual conferences: Shanghai Bird Translation and Consulting; Financial Interests, Personal, Invited Speaker, Invited speaker at virtual symposium: China International Medical Foundation; Financial Interests, Personal, Invited Speaker, Invited to speak and moderate at JLCS meetings: Japanese Lung Cancer Society; Financial Interests, Personal, Invited Speaker, Presented at several CME conferences: Medical Educator Consortium; Financial Interests, Personal, Invited Speaker, Facilitated discussion of recent data: IDEOlogy Health; Financial Interests, Personal, Invited Speaker, Invited CME lecture: Vindico Medical Education; Financial Interests, Personal, Invited Speaker, CME lecture: ParadigmMC; Financial Interests, Personal, Invited Speaker, CME lecture: Prova Education; Financial Interests, Personal, Invited Speaker, Invited speaker at symposium: Taiwan Association for the Study of Lung Cancer (TASLC); Financial Interests, Personal, Royalties, I receive royalties for a chapter I wrote for UpToDate: UpToDate; Financial Interests, Institutional, Local PI, Clinical Trial Conduct: AstraZeneca/Medimmune; Financial Interests, Institutional, Local PI, Clinical Trial Conduct: BMS; Financial Interests, Institutional, Steering Committee Member, Clinical Trial Conduct: Genentech/Roche; Financial Interests, Institutional, Steering Committee Member, Clinical Trial Conduct: Merck; Financial Interests, Institutional, Local PI, Clinical Trial Conduct: Seagen; Financial Interests, Institutional, Local PI, Clinical Trial Conduct: Xcovery; Financial Interests, Institutional, Local PI, clinical trial conduct: Helsinn; Financial Interests, Institutional, Coordinating PI, IIT for single site: Bayer; Financial Interests, Personal, Steering Committee Member, uncompensated steering committee member: Merck; Financial Interests, Personal, Other, uncompensated advisory board participation: BMS; Financial Interests, Personal, Steering Committee Member, uncompensated steering committee member: AstraZeneca; Financial Interests, Personal, Steering Committee Member, uncompensated steering committee member: Genentech/Roche; Non-Financial Interests, Personal, Officer, Past President: International Association for the Study of Lung Cancer (IASLC); Non-Financial Interests, Personal, Leadership Role, Executive Committee: ECOG-ACRIN. All other authors have declared no conflicts of interest.