Abstract 973MO
Background
Pembro + pem-platinum significantly improved survival vs pbo + pem-platinum in patients (pts) with previously untreated, metastatic nonsquamous NSCLC without sensitizing EGFR/ALK alterations, regardless of PD-L1 TPS, in the phase III KEYNOTE-189 study (NCT02578680). We report updated results with ∼5 y of follow-up.
Methods
Pts were randomized 2:1 to receive pembro 200 mg or pbo Q3W for up to 35 cycles (2y). All pts also received pem and investigator’s choice of carboplatin/cisplatin for 4 cycles, followed by maintenance pem until PD/unacceptable toxicity. Crossover from the pbo + pem-platinum group to pembro monotherapy was permitted after PD. Primary endpoints were OS and PFS.
Results
Among 616 pts randomized (pembro + pem-platinum, n = 410; pbo + pem-platinum, n = 206), median time from randomization to data cutoff (Mar 8, 2022) was 64.6 (range, 60.1–72.4) mo. 116/202 (57.4%) treated pts crossed over from pbo + pem-platinum to anti–PD-(L)1 therapy during/outside the study. Median (95% CI) OS was 22.0 (19.5‒24.5) mo vs 10.6 (8.7‒13.6) mo with pembro + pem-platinum vs pbo + pem-platinum (HR, 0.60; 95% CI, 0.50‒0.72) and 5-y OS rates were 19.4% vs 11.3%, respectively. Median (95% CI) PFS was 9.0 (8.1‒10.4) mo vs 4.9 (4.7‒5.5) mo (HR, 0.50; 95% CI, 0.42‒0.60). Additional efficacy results are in the table. Among pts with ≥1 dose of assigned treatment, grade 3‒5 AEs occurred in 295/405 (72.8%) vs 136/202 (67.3%) of pts. Among 57 pts who completed 35 cycles of pembro, ORR was 86.0% (CR, n = 8; PR, n = 41); 3-y OS rate after completion of 35 cycles of pembro was 71.9%.
Conclusions
First-line pembro + pem-platinum continued to show OS and PFS benefits with manageable toxicity vs pbo + pem-platinum, irrespective of PD-L1 expression. Pts who completed 35 cycles of pembro experienced durable responses. These data further support pembro + pem-platinum as a standard of care for metastatic nonsquamous NSCLC without sensitizing EGFR/ALK alterations. Table: 973MO
| ITTN = 616 | TPS ≥50% n = 202 | TPS 1%‒49% n = 186 | TPS <1% n = 190 | |
| OS HR (95% CI)a | 0.60 (0.50–0.72) | 0.68 (0.49–0.96) | 0.65 (0.46–0.90) | 0.55 (0.39–0.76) |
| 5-y OS ratea,% | 19.4 vs 11.3 | 29.6 vs 21.4 | 19.8 vs 7.7 | 9.6 vs 5.3 |
| PFS HR (95%CI)a,b | 0.50 (0.42–0.60) | 0.35 (0.25–0.49) | 0.57 (0.41–0.80) | 0.67 (0.49–0.92) |
| ORRb, % | 48.3 vs 19.9 | 62.1 vs 25.7 | 50.0 vs 20.7 | 33.1 vs 14.3 |
| Median DORa,b mo (range) | 12.7 (1.1+ to 68.3+) vs 7.1 (2.4 to 31.5) | 15.3 (1.2+ to 68.3+) vs 7.1 (3.4 to 31.5) | 13.6 (2.1+ to 67.6+) vs 7.6 (2.4 to 31.0+) | 10.8 (1.1+ to 59.4+) vs 7.8 (4.1 to 28.3+) |
+, no PD at last follow up; DOR, duration of response. Data are for pembro + pem-platinum vs pbo + pem-platinum. aK-M estimate. bPer RECIST v1.1 by blinded independent central review.
Clinical trial identification
NCT02578680.
Editorial acknowledgement
Writing support was provided by Christabel Wilson, MSc, of ICON plc (Blue Bell, PA, USA), and 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.C. Garassino: Financial Interests, Personal, Research Grant: Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA, AstraZeneca, Novartis, Bristol Myers Squibb, Roche, Pfizer, Celgene, Bayer, Tiziana Life Sciences, Clovis, Merck Serono, GlaxoSmithKline, Spectrum Pharmaceuticals, Eli Lilly. S.M. Gadgeel: Financial Interests, Personal, Other, personal fees: Merck, AstraZeneca, Genentech/Roche, Takeda/Ariad, Novocure, Bristol-Myers Squibb, AbbVie, Xcovery, Janssen, Pfizer, Jazz Pharmaceuticals, Blueprint, Lilly. E. Felip: Financial Interests, Personal, Advisory Role: AbbVie, AstraZeneca, Blueprint Medicines, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly, Guardant Health, Janssen, Medscape, Merck KGaA, Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA, Novartis, Pfizer, Roche; Financial Interests, Personal, Member of the Board of Directors: Grífols. E. Esteban Gonzalez: Financial Interests, Institutional, Research Grant: Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA. M. Domine Gomez: Financial Interests, Personal, Advisory Role: AstraZeneca, Bristol Myers Squibb, Boehringer Ingelheim, MSD Oncology, Pfizer, Roche; Received funding for travel, accommodation, and expenses from AstraZeneca, Boehringer Ingelheim, Eli Lilly, Pfizer, Roche; Financial Interests, Institutional, Research Grant: Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA. M.J. Hochmair: Financial Interests, Institutional, Research Grant: Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA. S.F. Powell: Financial Interests, Institutional, Research Grant: Bristol Myers Squibb, Genentech, Incyte, Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA, Pfizer, Novartis, Seattle Genetics, Actuate, Vyriad, Sorrento; Financial Interests, Institutional, Advisory Role: Bristol Myers Squibb; Financial Interests, Institutional, Invited Speaker: Alkermes. H. Bischoff: Financial Interests, Institutional, Research Grant: Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA. N. Peled: Financial Interests, Personal, Research Grant: AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA, Novartis, Pfizer, Roche, NovellusDx, Foundation Medicine, Guardant360; Financial Interests, Institutional, Research Grant: Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA. F. Grossi: Financial Interests, Personal, Research Grant: AstraZeneca, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA, Novartis, Pierre Fabre, Pfizer, Roche, Sanofi, Takeda. M. Reck: Financial Interests, Personal, Advisory Role: Lilly, Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA, Merck Serono, Bristol Myers Squibb, AstraZeneca, Boehringer Ingelheim, Pfizer, Novartis, Roche/Genentech, AbbVie, Amgen, Mirati Therapeutics, Samsung Bioepis, Sanofi/Regen; Financial Interests, Personal, Speaker’s Bureau: Roche/Genentech, Lilly, Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA, Merck Serono, AstraZeneca, Bristol Myers Squibb, Boehringer Ingelheim, Celgene, Pfizer, Novartis, Amgen, Mirati Therapeutics, Sanofi-Aventis. R. Hui: Financial Interests, Personal, Advisory Role: AstraZeneca, BMS, Eli Lilly, Merck, Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA, Novartis, Oncosec, Pfizer, Roche, Seagen. E.B. Garon: Financial Interests, Personal, Advisory Board: Novartis, Merck, BMS, EMD Serono, Regeneron, Sanofi, Natera, Shionogi, ABL Bio, Xilio, GSK, Boehringer Ingelheim, Eisai, Gilead, Eli Lilly, Personalis; Financial Interests, Institutional, Invited Speaker: Novartis, Merck, EMD Serono, Eli Lilly, Genetech, Iovance, Neon, Mirati, AstraZeneca, BMS, ABL Bio; Non-Financial Interests, Advisory Role, Scientific Advisory Board: Lungevity. T. Kurata: Financial Interests, Personal, Advisory Role: Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA, Ono, Bristol Myers Squibb, AstraZeneca, Chugai, Eli Lilly, Boehringer Ingelheim; Financial Interests, Personal, Research Grant: Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA, AstraZeneca, Takeda, Bristol Myers Squibb, Novartis; Financial Interests, Institutional, Research Grant: Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA. J.E. Gray: Financial Interests, Personal, Research Grant: Array, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Eli Lilly, Genentech, Merck; Financial Interests, Institutional, Research Grant: Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA. P.O. Schwarzenberger: 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: Merck & Co., Inc., Rahway, NJ, USA. 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: Merck & Co., Inc., Rahway, NJ, USA. D. Rodriguez Abreu: Financial Interests, Personal, Advisory Role: Roche, AstraZeneca, Bristol Myers Squibb, Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA, Eli Lilly, Pfizer, Novartis; Financial Interests, Personal, Other, Travel expenses: Roche, Bristol Myers Squibb, Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA, Novartis; Financial Interests, Institutional, Research Grant: Bristol Myers Squibb. All other authors have declared no conflicts of interest.