120MO - Adjuvant Pembrolizumab versus Placebo for Early-Stage NSCLC After Resection and Optional Chemotherapy: Updated Results From PEARLS/KEYNOTE-091

Background

At second interim analysis (IA2) of the phase 3 PEARLS/KEYNOTE-091 study of completely resected stage IB–IIIA NSCLC per AJCC v7 (NCT02504372), pembrolizumab (pembro) as adjuvant therapy significantly improved DFS vs placebo (pbo) in the ITT population (HR, 0.76; 95% CI, 0.63–0.91; P = 0.0014); significance was not achieved in the PD-L1 TPS ≥50% population (0.82; 95% CI, 0.57–1.18; P = 0.14). We report results from IA3, the final DFS analysis.

Methods

Eligible pts aged ≥18 y with completely resected stage IB (T ≥4 cm), II, or IIIA NSCLC (AJCC v7), ECOG PS 0 or 1, and tumor sample for PD-L1 testing received optional adjuvant chemotherapy (chemo) for ≤4 cycles as indicated per guidelines. Pts were randomized 1:1 to pembro 200 mg or pbo Q3W for 18 doses (∼1 y). Dual primary endpoints were DFS in the ITT and PD-L1 TPS ≥50% populations. Alpha was assigned to the PD-L1 TPS ≥50% population only (α = 0.0125; significance boundary, P = 0.01038).

Results

Of 1177 pts in the ITT population, 590 were randomized to pembro and 587 to pbo. Median follow-up at data cutoff (Jan 24, 2023) was 51.7 (range, 32.7–84.2) mo. DFS was not significantly improved with pembro vs pbo in the PD-L1 TPS ≥50% population (HR, 0.83; 95% CI, 0.59–1.16; P = 0.13); 4y DFS rates (95% CI) were 57.0% (47.9%–65.1%) vs 49.1% (39.8%–57.8%). Outcomes in the ITT and adjuvant chemo populations were generally consistent to IA2 (Table). 198 pts (34.1%) in the pembro group and 150 (25.8%) in pbo group experienced grade ≥3 all-cause AEs; 11 (1.9%) and 6 (1.0%), respectively, had grade 5 AE. 227 (39.1%) and 76 pts (13.1%), respectively, experienced immune-mediated AEs and infusion reactions. Table: 120MO

Conclusions

In this final DFS analysis, adjuvant pembro continued to improve DFS vs pbo in the ITT population, without significant improvement in pts with PD-L1 TPS ≥50%, in stage IB-IIIA NSCLC following complete resection and adjuvant chemo when indicated. Adjuvant pembro has manageable safety, supporting its use in this setting.

Clinical trial identification

NCT02504372.

Editorial acknowledgement

Medical writing support was provided by Kathleen Estes, PhD, of ICON plc (Blue Bell, PA, 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

B. Besse: Non-Financial Interests, Institutional, Research Grant: 4D Pharma (Inst); AbbVie (Inst); Amgen (Inst); Aptitude Health (Inst); AstraZeneca (Inst); BeiGene (Inst); Blueprint Medicines (Inst); Boehringer Ingelheim (Inst); Celgene (Inst); Cergentis (Inst); Chugai Pharma (Inst); Cristal Therapeutics (Inst); Daiich. L. Havel: Financial Interests, Institutional, Funding: Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA (MSD) to support conduct of this study; Financial Interests, Personal, Advisory Board: AstraZeneca; Bristol Myers Squibb; MSD; Pfizer; Roche; Sanofi; Takeda, Pierre Fabre Medicament. S. Peters: Financial Interests, Institutional, Funding: AstraZeneca (Inst); Bristol Myers Squibb (Inst); Ecancer (Inst); Illumina (Inst); Imedex (Inst); Medscape (Inst); MSD (Inst); Novartis (Inst); PER (Inst); Pfizer (Inst); Prime Oncology (Inst); Research to Practice (Inst); RMEI Medical Education (Inst); Ro; Financial Interests, Institutional, Advisory Board: AbbVie (Inst); Amgen (Inst); AstraZeneca (Inst); Bayer (Inst); Biocartis (Inst); Bioinvent (Inst); Blueprint Medicines (Inst); Boehringer Ingelheim (Inst); BristolMyers Squibb (Inst); Clovis Oncology (Inst); Daiichi Sankyo (Inst); Debiopharm Group (Inst); Financial Interests, Institutional, Research Funding: Amgen (Inst); AstraZeneca (Inst); Biodesix (Inst); BMS (Inst); Boehringer Ingelheim (Inst); Illumina (Inst); Iovance Biotherapeutics (Inst); Lilly (Inst); Merck Serono (Inst); MSD (Inst); Novartis (Inst); Pfizer (Inst); Phosplatin Therapeutics (Inst); Roc; Non-Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Bristol Myers Squibb; Incyte; MSD; Roche; Sanofi; Non-Financial Interests, Personal, Other, Uncompensated Relationships: Annals of Oncology (I); ESMO; European Thoracic Oncology Platform (ETOP); Journal of Thoracic Oncology. S.I. Marreaud, N. Jha, U. Dafni, M.E. Mauer: Financial Interests, Institutional, Research Funding: Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA. K. Oselin: Financial Interests, Institutional, Local PI: Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA; Financial Interests, Institutional, Funding: Pfizer and Takeda; Financial Interests, Personal, Advisory Board: Amgen, Takeda, MSD, Janssen, Roche, and AstraZeneca; Financial Interests, Personal, Other, travel: MSD and AstraZeneca. E. Esteban Gonzalez: Financial Interests, Institutional, Local PI: Merck Sharp & Dohme LLC. M.D. Isla Casado: Financial Interests, Personal, Advisory Board: Amgen; AstraZeneca; Bayer; Boehringer Ingelheim; Bristol Myers Squibb; GSK; Janssen; Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA (MSD); Pfizer; Roche; Sanofi; Takeda; ; Financial Interests, Personal, Speaker, Consultant, Advisor: Amgen; AstraZeneca; Bayer; Bristol Myers Squibb; MSD; Pfizer; Roche; Takeda; ; Financial Interests, Institutional, Research Funding: GSK (Inst); MSD (Inst). A. Martinez-Marti: Financial Interests, Personal, Advisory Board: AstraZeneca/MedImmune; Boehringer Ingelheim; Bristol Myers Squibb; Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA (MSD); MSD Oncology; Pfizer; Roche; Financial Interests, Personal, Speaker, Consultant, Advisor: AstraZeneca/MedImmune; Boehringer Ingelheim; Bristol Myers Squibb; Merck Sharp & Dohme; Pfizer; Roche; Financial Interests, Personal, Other, travel: AstraZeneca/MedImmune; Boehringer Ingelheim; Bristol Myers Squibb; Merck Sharp & Dohme; Pfizer; Roche; Financial Interests, Institutional, Research Funding: MSD. M. Faehling: Financial Interests, Personal, Advisory Board: AstraZeneca; Bristol Myers Squibb; Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA (MSD); Roche; Financial Interests, Personal, Speaker, Consultant, Advisor: AstraZeneca; Bristol Myers Squibb; Roche; Sanofi; Financial Interests, Institutional, Research Funding: AstraZeneca (Inst); MSD (Inst); Roche (Inst). J. Lee: Financial Interests, Institutional, Research Funding: Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA. Y. Luo, S.M. Keller: Financial Interests, Personal, Full or part-time Employment: Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA. R.A. Stahel: Financial Interests, Personal, Advisory Board: AstraZeneca; Boehringer Ingelheim; Bristol Myers Squibb; GSK; Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA (MSD); Roche; Sandoz; Seattle Genetics; Takeda; Financial Interests, Personal, Speaker, Consultant, Advisor: Amgen; AstraZeneca; Blueprint Medicines; Boehringer Ingelheim; Bristol Myers Squibb; GSK; MSD; Novartis; Roche; Financial Interests, Institutional, Research Funding: AstraZeneca (Inst); Bristol Myers Squibb (Inst); Celgene (Inst); Daiichi Sankyo (Inst); Ipsen (Inst); Janssen (Inst); MSD (Inst); Mirati Therapeutics (Inst); Novartis (Inst); Pfizer (Inst); Pierre Fabre (Inst); Roche (Inst). M.E.R. O'Brien: Financial Interests, Personal, Financially compensated role, honoraria: AbbVie; Bristol Myers Squibb; Merck & Co., Inc., Rahway, NJ, USA; Merck Serono; Financial Interests, Personal, Advisory Board: Amgen; AstraZeneca; Eisai Europe; ITeos Therapeutics; Merck & Co., Inc., Rahway, NJ, USA; PharmaMar; Pierre Fabre; Puma Biotechnology; Financial Interests, Personal, Other, travel: Bristol Myers Squibb; Financial Interests, Institutional, Research Funding: MSD. M. Tsuboi: Financial Interests, Personal, Financially compensated role, honoraria: AstraZeneca Japan; Bristol Myers Squibb Japan; Chugai Pharma; Johnson & Johnson; Lilly Japan; Medtronic; MSD K.K., Tokyo, Japan; Novartis; Ono Pharmaceutical; Taiho Pharmaceutical; Teijin Pharma; Daiichi Sankyo Company; Financial Interests, Personal, Advisory Board: AstraZeneca Japan; Chugai Pharma; Lilly Japan; MSD; Novartis; MiRXES; ; Financial Interests, Institutional, Research Funding: AstraZeneca Japan (Inst); Bristol Myers Squibb KK (Inst); Merck & Co., Inc., Rahway, NJ, USA (Inst); Ono Pharmaceutical (Inst); Novartis (Inst); MiRXES (Inst); Johnson & Johnson Japan (Inst). L. Paz-Ares: Financial Interests, Personal, Advisory Board, or speaker: Adacap, Amgen, AstraZeneca, Bayer, Blueprint Medicines, BMS, Boehringer Ingelheim, Celgene, Incyte, Ipsen, Lilly, Merck KGaA, Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA to, Novartis, PharmaMar, Pfizer, Roche, Sanofi, Servi; Financial Interests, Personal, Member of Board of Directors: Genómica and Altum Sequencing; Financial Interests, Institutional, Research Funding: AstraZeneca, BMS, Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA, and Pfizer.