930MO - PD-L1 expression and outcomes of pembrolizumab and placebo in completely resected stage IB-IIIA NSCLC: Subgroup analysis of PEARLS/KEYNOTE-091

Background

In the PEARLS/KEYNOTE-091 study of completely resected stage IB (T ≥4 cm) to IIIA NSCLC (AJCC v7) following ≤4 cycles of adjuvant chemotherapy as recommended per local guidelines (NCT02504372), pembrolizumab (pembro) significantly prolonged DFS vs placebo in the ITT population at the second interim analysis (IA2) (HR 0.76; P = 0.0014). The DFS benefit in the PD-L1 TPS ≥50% population was not significant (HR 0.82; P = 0.14). We present more detailed results for the PD-L1 subgroups.

Methods

Eligible patients were randomized 1:1 to pembro 200 mg or placebo Q3W for 18 doses. PD-L1 TPS <1% vs 1-49% vs ≥50% was a stratification factor. Dual primary end points were DFS in the ITT and TPS ≥50% populations. Data are from IA2 (median follow-up, 35.6 months).

Results

Of the 1177 randomized patients, PD-L1 TPS was <1% in 39.5%, 1-49% in 32.2%, and ≥50% in 28.3%. Baseline characteristics were generally balanced between the pembro and placebo arms in the ITT and TPS ≥50% populations and were generally similar in the ITT and TPS ≥50% populations. Grade 3-5 AE rates for pembro vs placebo were 34.1% vs 25.8% in the ITT and 37.8% vs 25.0% in the TPS ≥50% population; AEs led to discontinuation in 19.8% vs 5.9% and 23.2% vs 6.7%. Pembro improved DFS in the TPS ≥50%, 1-49%, and <1% subgroups (Table). Table: 930MO

*Dual primary end point; P = 0.14.

Conclusions

As expected, median and long-term DFS estimates in the pembro arm were numerically improved in the PD-L1 TPS ≥50% subgroup vs the 1-49% and <1% subgroups. The lack of statistically significant benefit for pembro in the TPS ≥50% population at IA2 likely results from placebo overperformance in this population and a smaller population size. DFS in the PD-L1-selected populations will be tested at the next IA. Overall, data support the benefit of pembro for completely resected stage IB-IIIA NSCLC and, if recommended, adjuvant chemotherapy, regardless of PD-L1 expression.

Clinical trial identification

NCT02504372, first posted on July 21, 2015.

Editorial acknowledgement

Medical writing and editorial assistance provided by Melanie Leiby, an employee of the study sponsor, Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.

Legal entity responsible for the study

EORTC Lung Cancer Group and ETOP.

Funding

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

Disclosure

S. Peters: Financial Interests, Institutional, Advisory Board: Vaccibody, Takeda, Seattle Genetics, Sanofi, Roche/Genentech, Regeneron, Phosplatin Therapeutics, PharmaMar, Pfizer, Novartis, Mirati, Merck Serono, MSD, Janssen, Incyte, Illumina, IQVIA, GlaxoSmithKline, Gilhead, Genzyme, Foundation Medicine, F-Star, Eli Lilly, Debiopharm, Daiichi Sankyo, Boehringer Ingelheim, Blueprint Medicines, Biocartis, Bio Invent, BeiGene, Bayer, BMS, AstraZeneca, Arcus, Amgen, AbbVie, iTheos, Novocure; Financial Interests, Institutional, Invited Speaker: Takeda, Sanofi, Roche/Genentech, RTP, Pfizer, PRIME, PER, Novartis, Medscape, MSD, Imedex, Illumina, Fishawack, Eli Lilly, Ecancer, Boehringer Ingelheim, AstraZeneca, BMS, OncologyEducation, RMEI, Mirati; Financial Interests, Personal, Other, Associate Editor Annals of Oncology: Elsevier; Financial Interests, Institutional, Invited Speaker, MERMAID-1: AstraZeneca; Financial Interests, Institutional, Invited Speaker, MERMAID-2, Poseidon, MYSTIC: AstraZeneca; Financial Interests, Institutional, Invited Speaker, Clinical Trial Steering committee CheckMate 743, CheckMate 73L, CheckMate 331 and 451: BMS; Financial Interests, Institutional, Invited Speaker, RELATIVITY 095: BMS; Financial Interests, Institutional, Invited Speaker, BGB-A317-A1217-301/AdvanTIG-301: BeiGene; Financial Interests, Institutional, Invited Speaker, Clinical Trial Chair ZEAL-1: GSK; Financial Interests, Institutional, Invited Speaker, Clinical Trial Steering Committee PEARLS, MK-7684A: MSD; Financial Interests, Institutional, Invited Speaker, Clinical Trial Steering Committee SAPPHIRE: Mirati; Financial Interests, Institutional, Invited Speaker, LAGOON: PharmaMar; Financial Interests, Institutional, Invited Speaker, phase 1/2 trials: Phosplatin Therapeutics; Financial Interests, Institutional, Invited Speaker, Clinical Trial Chair Skyscraper-01; Chair ALEX; Steering Committee BFAST; Steering Committee BEAT-Meso; Steering Committee ImPower-030, IMforte: Roche/Genentech; Financial Interests, Institutional, Invited Speaker, Phase 2 Inupadenant with chemo: iTeos; Non-Financial Interests, Officer, ESMO President 2020-2022: ESMO; Non-Financial Interests, Officer, Council Member & Scientific Committee Chair: ETOP/IBCSG Partners; Non-Financial Interests, Officer, Vice-President Lung Group: SAKK; Non-Financial Interests, Other, Involved in Swiss politics: Swiss Political Activities; Non-Financial Interests, Officer, President and Council Member: Ballet Béjart Lausanne Foundation; Non-Financial Interests, Principal Investigator, Involved in academic trials: ETOP/EORTC/SAKK; Non-Financial Interests, Member: Association of Swiss Physicians FMH (CH), ASCO, AACR, IASLC; Non-Financial Interests, Leadership Role, ESMO President: ESMO; Non-Financial Interests, Member, Vice-President Lung Group: SAKK; Non-Financial Interests, Leadership Role, Vice-President: SAMO; Non-Financial Interests, Member, Association of Swiss interns and residents: ASMAC/VSAO. B. Besse: Financial Interests, Institutional, Funding: 4D Pharma, AbbVie, Amgen, Aptitude Health, AstraZeneca, BeiGene, Blueprint Medicines, Boehringer Ingelheim, Celgene, Cergentis, Cristal Therapeutics, Daiichi-Sankyo, Eli Lilly, GSK, Janssen, Onxeo, OSE immunotherapeutics, Pfizer, Roche-Genentech, Sanofi, Takeda, Tolero Pharmaceuticals; Financial Interests, Institutional, Research Grant: Chugai pharmaceutical, Eisai, Genzyme Corporation, Inivata, Ipsen, Turning Point Therapeutics. U. Dafni: Financial Interests, Personal, Other, Member of the Tumor Agnostic Evidence Generation working Group: Roche. K. Oselin: Financial Interests, Personal, Advisory Board: MSD, Takeda, AstraZeneca, Janssen, Amgen, Roche; Financial Interests, Institutional, Research Grant: Takeda, Roche, Pfizer. D. Isla: Financial Interests, Institutional, Research Grant: GSK; Financial Interests, Personal, Advisory Role: MSD, AstraZeneca, Roche, Amgen, Pfizer, Sanofi, Bayer, Bristol-Myers Squibb, GSK, Janssen, Takeda, BI; Financial Interests, Personal, Speaker’s Bureau: Amgen, AstraZeneca, Bayer, Bristol-Myers Squibb, Roche, MSD, Pfizer, Takeda. A. Martinez-Marti: Financial Interests, Personal, Advisory Board, Speaker's Bureau: Bristol-Myers Squibb, F. Hoffmann La Roche AG, Merck Sharp & Dohme, MSD Oncology, AstraZeneca/MedImmune; Financial Interests, Personal, Other, Speaker's Bureau: Pfizer; Financial Interests, Personal, Invited Speaker, And Local PI: AstraZeneca/MedImmune; Financial Interests, Personal, Invited Speaker: F. Hoffmann La Roche AG, Bristol-Myers Squibb, Merck Sharp & Dohme, MSD Oncology; Non-Financial Interests, Principal Investigator: AstraZeneca/MedImmune, F. Hoffmann La Roche AG, Bristol-Myers Squibb, Merck Sharp & Dohme, MSD Oncology. M. Faehling: Financial Interests, Institutional, Funding: MSD, Roche, AstraZeneca; Financial Interests, Personal, Advisory Board: MSD, Roche, AstraZeneca, Bristol Myers Squibb; Financial Interests, Personal, Invited Speaker: Roche, AstraZeneca, Sanofi, Bristol Myers Squibb. 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, Teijin Pharma, Taiho Pharma, Medtronic Japan, ONO Pharmaceutical CO., LTD; Financial Interests, Personal, Advisory Board, Advisory boards: Novartis; Financial Interests, Personal, Invited Speaker: Daiichi-Sankyo Company Limited, MSD, AstraZeneca, Novartis; Financial Interests, Institutional, Research Grant: Beohringer-Ingelheim Japan, MSD, AstraZeneca KK, Ono Pharmaceutical CO., LTD, Bristol-Myers Squibb KK, Novartis; Financial Interests, Institutional, Invited Speaker: Eli Lilly Japan. K. Nakagawa: Financial Interests, Personal, Invited Speaker: Ono Pharmaceutical Co., Ltd., Eli Lilly Japan K.K., Amgen Inc., Nippon Kayaku Co., Ltd., AstraZeneca K.K., Chugai Pharmaceutical Co., Ltd., MSD K.K., Pfizer Japan Inc., Nippon Boehringer Ingelheim Co., Ltd., Taiho Pharmaceutical Co., Ltd., Bayer Yakuhin, Ltd., CMIC ShiftZero K.K., Life Technologies Japan Ltd., Neo Communication, Merck Biopharma Co., Ltd., Kyowa Kirin Co., Ltd., Takeda Pharmaceutical Co., Ltd., 3H Clinical Trial Inc., Care Net, Inc., Medical Review Co., Ltd., Medical Mobile Communications co., Ltd, YODOSHA CO., LTD., Nikkei Business Publications, Inc., Japan Clinical Research Operations, CMIC Co., Ltd., Novartis Pharma K.K., Taiyo Pharma Co., Ltd.; Financial Interests, Personal, Advisory Board: Ono Pharmaceutical Co., Ltd., Eli Lilly Japan K.K.; Financial Interests, Institutional, Other, patents sales fee: Daiichi Sankyo Co., Ltd.; Financial Interests, Institutional, Research Grant: Parexel International Corp., PRA Healthsciences, EPS Corporation., Kissei Pharmaceutical Co., Ltd., EPS International Co.,Ltd,., Daiichi Sankyo Co., Ltd., Taiho Pharmaceutical Co.,Ltd., MSD K.K., Ono Pharmaceutical Co.,Ltd., PPD-SNBL K.K, SymBio Pharmaceuticals Limited., IQVIA Services Japan K.K., Syneos Health Clinical K.K., Nippon Kayaku Co.,Ltd., EP-CRSU Co., Ltd., Mebix, Inc., Bristol-Myers Squibb K.K., Janssen Pharmaceutical K.K., Eisai Co., Ltd., AstraZeneca K.K., Mochida Pharmaceutical Co., Ltd., Covance Japan Inc., Japan Clinical Research Operations, Takeda Pharmaceutical Co., Ltd., GlaxoSmithKline K.K., Sanofi K.K., Chugai Pharmaceutical Co., Ltd., Nippon Boehringer Ingelheim Co., Ltd., Sysmex Corporation, Medical Research Support, Eli Lilly Japan K.K., Amgen Inc., Novartis Pharma K.K., Novartis Pharma K.K., SRL, Inc. J. Yang: Financial Interests, Personal, Full or part-time Employment: Merck Sharp & Dohme Corp. S.M. Keller: Financial Interests, Personal, Full or part-time Employment: Merck Sharp & Dohme Corp.; Financial Interests, Personal, Stocks/Shares: Merck Sharp & Dohme Corp. R.A. Stahel: Financial Interests, Personal, Invited Speaker: Amgen, AstraZeneca, Blueprint, Boehringer Ingelheim, GSK, MSD, Novartis, Roche, BMS; Financial Interests, Personal, Advisory Board: AstraZeneca, BMS, Janssen, MSD, Pfizer, Roche, Sandoz, Seattle Genetics, Takeda, Boehringer Ingelheim, GSK; Financial Interests, Personal, Other, DMC: Takeda; Financial Interests, Personal, Other, Editor in Chief: Lung Cancer; Financial Interests, Personal, Other, Editor: CTR; Financial Interests, Institutional, Research Grant, ETOP study: Roche, AstraZeneca, BMS, MSD, Pfizer, Mirati, Janssen; Financial Interests, Institutional, Research Grant, IBCSG study: Novartis, Ipsen, Piere Fabre, MSD, Pfizer, Roche, AstraZeneka, Celgene; Non-Financial Interests, Invited Speaker, PresidentFoundation Council: IBCSG, ETOP. L. Paz-Ares: Financial Interests, Personal, Advisory Board, Speaker fees: Roche, MSD, BMS, AZ, Lilly, PharmaMar, BeiGene, Daiichi, Medscape, PER; Financial Interests, Personal, Advisory Board: Merck Serono, Pfizer, Bayer, Amgen, Janssen, GSK, Novartis, Takeda, Sanofi, Mirati; Financial Interests, Personal, Other, Board member: Genomica, Altum sequencing; Financial Interests, Institutional, Invited Speaker: Daiichi Sankyo, AstraZeneca, Merck Sharp & Dohme Corp, BMS, Janssen-cilag international NV, Novartis, Roche, Sanofi, Tesaro, Alkermes, Lilly, Takeda, Pfizer, PharmaMar; Financial Interests, Personal, Invited Speaker: Amgen; Financial Interests, Other, Member: AACR, ASCO, ESMO; Financial Interests, Other, Foundation Board Member: AECC; Financial Interests, Other, President ASEICA (Spanish Association of Cancer Research): ASEICA; Financial Interests, Other, Foundation president: ONCOSUR; Financial Interests, Other, Member: Small Lung Cancer Group. M.E.R. O'Brien: Financial Interests, Personal, Advisory Board, virtual ad board: Puma, Sanofi; Financial Interests, Personal, Advisory Board: iTeos, Amgen, MSD, Pierre Fabre; Financial Interests, Institutional, Invited Speaker, we host clinical trials, PI for MSD pearls trial: MSD; Non-Financial Interests, Advisory Role: Eisai; Chair this UK Research Group: NCRI CSG LORD Subgroup. All other authors have declared no conflicts of interest.