Abstract 1210P
Background
Neoadjuvant pembro + chemo followed by adjuvant pembro significantly improved event-free survival (EFS) and OS vs neoadjuvant chemo alone in patients (pts) with resectable NSCLC in the phase III KEYNOTE-671 study. At interim analysis 2 (IA2), HRs (95% CI) were 0.59 (0.48–0.72) for EFS and 0.72 (0.56–0.93) for OS. We present EFS and OS results for key pt subgroups based on IA2.
Methods
Eligible pts with resectable stage II, IIIA, or IIIB (N2) NSCLC per AJCC 8 were randomized 1:1 to 4 cycles of pembro 200 mg or pbo + cisplatin-based chemo followed by surgery and adjuvant pembro or pbo for up to 13 additional cycles. Dual primary endpoints were EFS by investigator assessment per RECIST v1.1 and OS. Randomization was stratified by disease stage (II vs III), PD-L1 TPS (<50% vs ≥50%), histology (squamous vs nonsquamous), and region (East Asia vs non–East Asia). Exploratory analyses of EFS and OS were done using a Cox regression model with treatment as a covariate for preplanned subgroups based on PD-L1 TPS, disease stage, nodal involvement, and histology at baseline. Landmark analyses of EFS and OS from time of initiation of adjuvant therapy were also done.
Results
797 pts were randomized to the pembro arm (N = 397) or the pbo arm (N = 400). Median study follow-up at IA2 (data cutoff, July 10, 2023) was 36.6 mo (range, 18.8–62.0). HRs for EFS and OS favored the pembro arm across all subgroups evaluated (Table). Among pts who started adjuvant therapy, HRs (95% CI) for EFS and OS from the start of adjuvant therapy were 0.55 (0.42–0.72; N = 548) and 0.71 (0.49–1.03; N = 557), respectively. Table: 1210P
| N | EFS HR (95% CI) | OS HR (95% CI) | |
| Stage II at baseline | 239 | 0.59 (0.40–0.88) | 0.67 (0.41–1.10) |
| Stage III at baseline | 558 | 0.58 (0.46–0.72) | 0.74 (0.55–0.98) |
| Squamous histology | 344 | 0.51 (0.38–0.69) | 0.71 (0.51–0.99) |
| Nonsquamous histology | 453 | 0.66 (0.51–0.86) | 0.73 (0.50–1.06) |
| PD-L1 TPS ≥50% | 266 | 0.48 (0.33–0.71) | 0.55 (0.33–0.92) |
| PD-L1 TPS 1%–49% | 242 | 0.52 (0.36–0.73) | 0.69 (0.44–1.07) |
| PD-L1 TPS ≥1% | 508 | 0.51 (0.39–0.66) | 0.62 (0.45–0.87) |
PD-L1 TPS ConclusionsPerioperative pembro provided a clinically meaningful improvement in EFS and OS across subgroups vs neoadjuvant chemo alone in pts with resectable stage II, IIIA, or IIIB NSCLC. Results from the landmark analyses from time of adjuvant therapy start suggest adjuvant therapy adds clinical benefit in this setting. Clinical trial identificationNCT03425643; EudraCT 2017-001832-21. Editorial acknowledgementMedical writing assistance was provided by Christabel Wilson, MSc, of ICON plc (Blue Bell, PA, USA). This assistance was funded by Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA. Legal entity responsible for the studyMerck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA. FundingMerck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA. DisclosureM.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; 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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: Merck. 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. J.D. Spicer: Financial Interests, Personal, Advisory Board: AstraZeneca, Merck, Roche, BMS, Novartis, Amgen, Protalix Biotherapeutics, Xenetic Biosciences, Regeneron, Eisai; Financial Interests, Personal, Invited Speaker: AstraZeneca, Merck, BMS; Financial Interests, Institutional, Coordinating PI, In kind contribution of investigational drug.: AstraZeneca, BMS; Financial Interests, Institutional, Coordinating PI, Grant to institution for research within my laboratory.: CLS Therapeutics; Financial Interests, Institutional, Coordinating PI, Grant to institution for execution of research within my laboratory.: Protalix Biotherapeutics; Financial Interests, Institutional, Coordinating PI, Grant to institution for execution of multi-center clinical trial.: Roche; Financial Interests, Institutional, Coordinating PI, Grant to institution for execution of clinical trial.: Merck; Non-Financial Interests, Principal Investigator, Clinical trial chair for IND 242 Neoadjuvant Platform Trial in Patients with Surgically Resectable Non-Small Cell Lung Cancer (NSCLC): Canadian Cancer Trials Group. L. Thiberville: Financial Interests, Institutional, Other, Board and expertise, invitation to medical congress: MSD, Sanofi, Chiesi, Pfizer. F.D.F. Chaves: Financial Interests, Institutional, Other, Local PI or SI of clinical trials: AstraZeneca, MSD, Xcovery, BMS, Lilly, Beigene; Financial Interests, Institutional, Invited Speaker, Local speaker: AstraZeneca, Servier, Takeda, Merck, MSD, Bayer. G. Liu: Financial Interests, Personal, Advisory Board: Anheart, Amgen, AstraZeneca, Bayer, EMD Serono, Jazz, Johnson and Johnson, MSD, Novartis, Pfizer, Roche, Sterimax, Takeda; Financial Interests, Personal and Institutional, Coordinating PI: Takeda, AstraZeneca. Research grants from Boehringer Ingelheim, Pfizer, AstraZeneca, Takeda. M. Okada: Financial Interests, Institutional, Funding, Funding for this study: MSD. H. Saji: Financial Interests, Personal and Institutional, Other, Payment or honoraria for lectures, presentations, speaker bureaus, manuscript writing, or educational events: MSD, Chugai Pharmaceutical, Astellas Pharma, Takeda, AstraZeneca, CSL Behring, TAIHO, Bristol Myers Squibb, Fujifilm Medical, Ethicon, and Covidien. K. Laktionov: Financial Interests, Personal, Invited Speaker, Speaker’s Bureau: AstraZeneca, Roche, Biocad, Pfeizer, Amgen, Swixx BioPharma; Non-Financial Interests, Advisory Role: AstraZeneca, Roche, Biocad, Pfizer, Amgen. A. Rittmeyer: Financial Interests, Personal, Advisory Board: AbbVie, AstraZeneca, BMS, Boehringer Ingelheim, Daiichi Sankyo, Gilead, GSK, MSD, Eli Lilly, Novartis, Pfizer, Roche. J. Bosch-Barrera: Financial Interests, Personal, Invited Speaker: MSD, BMS, AstraZeneca; Financial Interests, Personal, Advisory Board: Roche, Sanofi; Other, Relative (sister in law) working for this company.: AstraZeneca. R.D. Gentzler: Financial Interests, Personal, Advisory Board: AstraZeneca, Takeda, Gilead, Janssen, Mirati, Daiichi Sankyo, Sanofi, Oncocyte, Jazz Pharmaceuticals, Merus; Financial Interests, Personal, Invited Speaker: Clinical Care Options, OncLive, Targeted Oncology, Society for Immunotherapy of Cancer (SITC), MedStar Health, Aptitude Health, American Society of Clinical Oncology (ASCO); Financial Interests, Institutional, Local PI: Janssen, Mirati, Daiichi Sankyo, Bristol Myers Squibb, AstraZeneca, Jounce Therapeutics, Takeda, Bristol Myers Squibb, Merck, Chugai, Amgen, Dizal; Financial Interests, Institutional, Research Grant: Pfizer; Financial Interests, Institutional, Coordinating PI: Mirati; Non-Financial Interests, Leadership Role, Co-chair, Thoracic Working Group: Hoosier Cancer Research Network; Non-Financial Interests, Principal Investigator: NCI ETCTN; Non-Financial Interests, Other, Member of Lung Cancer Scientific Review Committee: American Society of Clinical Oncology, Scientific Review Committee; Non-Financial Interests, Other, Committee Member: NCI Investigational Drug Steering Committee; Non-Financial Interests, Officer, Editor: Journal of Clinical Oncology: Meeting Abstracts; Non-Financial Interests, Other, World Conference on Lung Cancer 2024 Planning Committee: IASLC; Non-Financial Interests, Personal, Other, Travel support for attending meetings for invited speaker: International Association for the Study of Lung Cancer (IASLC); Non-Financial Interests, Personal, Other, Travel to meeting: Tempus, ASCO. A.K. Ganti: Financial Interests, Personal and Institutional, Coordinating PI, Institutional PI for clinical trials: MSD, Boehringer Ingelheim, Poseida Inc, Mirati Therapeutics; Financial Interests, Personal and Institutional, Speaker, Consultant, Advisor, Consultant: Jazz Pharmaceuticals, AstraZeneca, Regeneron Pharmaceuticals, Sanofi Genzyme, Cardinal Health, Flagship Biosciences, Mirati Therapeutics, Bayer. E. Jensen: Financial Interests, Personal, Full or part-time Employment: Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA; Financial Interests, Personal, Stocks/Shares, may own stock and/or hold stock options: Merck & Co., Inc., Rahway, NJ, USA. S.M. Keller: Financial Interests, Personal, Full or part-time Employment: Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA; Financial Interests, Personal, Stocks/Shares, may own stock and/or hold stock options: Merck & Co., Inc., Rahway, NJ, USA. A. Samkari: Financial Interests, Institutional, Full or part-time Employment: Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA; Financial Interests, Personal, Stocks/Shares, may own stock and/or hold stock options: Merck & Co., Inc., Rahway, NJ, USA. 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, 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, ParadigmMC, Prova 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, 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, BMS, Seagen, Xcovery; Financial Interests, Institutional, Steering Committee Member, Clinical Trial Conduct: Genentech/Roche, Merck; 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, AstraZeneca, Genentech/Roche; Financial Interests, Personal, Other, uncompensated advisory board participation: BMS; Non-Financial Interests, Officer, Past President: International Association for the Study of Lung Cancer (IASLC); Non-Financial Interests, Leadership Role, Executive Committee: ECOG-ACRIN. All other authors have declared no conflicts of interest. 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