974MO - 5-year update from KEYNOTE-407: Pembrolizumab plus chemotherapy in squamous non-small cell lung cancer (NSCLC)

Background

Pembrolizumab (pembro) + platinum-based chemotherapy (chemo) significantly prolonged OS and PFS compared with placebo + chemo in patients (pts) with previously untreated, metastatic squamous NSCLC in the phase III KEYNOTE-407 study (NCT02775435). We report the 5-y outcomes in the ITT population and in pts who completed 35 cycles of pembro (∼2 y).

Methods

Eligible pts were randomized 1:1 to receive pembro 200 mg or placebo + carboplatin and paclitaxel/nab-paclitaxel Q3W for 4 cycles, followed by pembro or placebo up to 35 cycles. Eligible pts in the placebo + chemo group were allowed to crossover on-study to up to 35 cycles of open-label pembro monotherapy upon unblinding after verification of PD by BICR. Primary endpoints were OS and PFS per RECIST v1.1 by BICR.

Results

Pts were randomized to pembro + chemo (n = 278) or placebo + chemo (n = 281). As of Feb 23, 2022, median time from randomization to data cutoff was 56.9 (range, 49.9–66.2) mo; 117 pts crossed over from the placebo + chemo group to receive pembro monotherapy, and an additional 26 pts received subsequent anti–PD-(L)1 therapy; the effective crossover rate was 51.1%. Median OS in the ITT population was 17.2 mo for the pembro + chemo group and 11.6 mo for the placebo + chemo group; HR, 0.71 (95% CI, 0.59–0.85). Respective 5-y OS rates were 18.4% and 9.7%. Additional efficacy outcomes are described in the table. Grade 3‒5 AEs occurred in 74.8% and 70.0% of pts in the pembro + chemo and placebo + chemo groups, respectively. Among 55 pts who completed 35 cycles of pembro, ORR was 90.9%, and 3-y OS rate after completion of 35 cycles (⁓5 y after randomization) was 69.5%. Table: 974MO

+ indicates no PD by time of last assessment.

Conclusions

After 5 y of follow-up, pembro + chemo continued to demonstrate prolonged OS and PFS vs chemo alone without increased toxicity. Most pts who completed 35 cycles had objective responses and were alive at data cutoff. These long-term data support use of pembro + chemo as a standard first-line treatment option for metastatic squamous NSCLC.

Clinical trial identification

NCT02775435.

Editorial acknowledgement

Writing support was provided by Kathleen Estes, PhD, 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

S. Novello: Financial Interests, Personal, Invited Speaker: AZ, MSD, Eli Lilly, Novartis, BeiGene, Amgen; Financial Interests, Personal, Advisory Board: BI, BMS, Pfizer, Takeda, Roche, Sanofi, Amgen; Financial Interests, Institutional, Invited Speaker, IIT: MSD, BI; Non-Financial Interests, Leadership Role, President of this European advocacy: WALCE. D.M. Kowalski: Financial Interests, Personal, Advisory Board: Bristol-Myers Squibb, Boehringer Ingelheim, Merck Serono, Roche/Genentech, AstraZeneca, Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA; Financial Interests, Institutional, Funding: Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Rahway, NJ, USA, to support study conduct. D. Vicente Baz: Financial Interests, Personal, Other, received honoraria to self/spouse for scientific advice: AstraZeneca, BMS, Boehringer Ingelheim, MSD, Pfizer, and Roche; Financial Interests, Personal, Invited Speaker: AstraZeneca, BMS, Boehringer Ingelheim, MSD, Pfizer, and Roche. J. Mazieres: Financial Interests, Personal, Invited Speaker: Roche, AstraZeneca, BMS, MSD, Daiichi, Novartis, Amgen; Financial Interests, Personal, Advisory Board: Roche, AstraZeneca, Pierre Fabre, Takeda, BMS, MSD, Jiangsu Hengruii, Blueprint, Daiichi, Novartis, Amgen, Lilly, Merck; Financial Interests, Personal, Research Grant: Roche, AstraZeneca, Pierre Fabre, BMS; Non-Financial Interests, Personal, Principal Investigator: Roche, AstraZeneca, Pierre Fabre, Takeda, BMS, MSD, Jiangsu Hengruii, Blueprint, Daiichi, Novartis, Amgen, Sanofi, Pfizer, Merck. J.R. Rodriguez Cid: Financial Interests, Institutional, Funding, received funding to the institution during conduct of this trial: MSD; Financial Interests, Institutional, Funding, received funding to the institution to support trial conduct: Bayer, BMS, Celgene, Eli Lilly, MSD, Novartis, and Roche. A. Tafreshi: Financial Interests, Institutional, Funding, support study conduct: Merck. Y. Cheng: Financial Interests, Institutional, Funding, support study conduct: Merck. K.H. Lee: Financial Interests, Personal, Advisory Board: Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA, AstraZeneca, Bristol-Myers Squibb, Pfizer, Lilly; Financial Interests, Institutional, Funding: Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Rahway, NJ, USA, to support study conduct. S. Sugawara: Financial Interests, Personal, Other, Honoraria: AstraZeneca, Bristol Myers Squibb, Chugai Pharma, Kyowa Kirin, Lilly, MSD K.K., Nippon Boehringer Ingelheim, Novartis, Ono Pharmaceuticals, Pfizer, Taiho Pharmaceuticals, and Yakult Honsha. A.G. Robinson: Financial Interests, Personal, Funding, received funding for clinical trials: AstraZeneca, Merck, Pfizer, and Roche; Financial Interests, Personal, Advisory Board: Merck. B. Halmos: Financial Interests, Personal, Funding, research funding: AbbVie, AstraZeneca, BMS, Boehringer Ingelheim, Eli Lilly, GSK, Guardant Health, Merck, Mirati, Novartis, Pfizer, and Takeda; Financial Interests, Personal, Other, consultant: AstraZeneca, BMS, Boehringer Ingelheim, Genentech, Guardant Health, Merck, Novartis, Pfizer, and Spectrum. 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. 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. M.C. Pietanza: 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. L. Paz-Ares: Financial Interests, Personal, Other, honoraria to self/spouse for scientific advice: Adacap, Amgen, AstraZeneca, Bayer, Blueprint Medicines, BMS, Boehringer Ingelheim, Celgene, Incyte, Ipsen, Lilly, Merck, MSD, Novartis, PharmaMar, Pfizer, Roche, Sanofi, Servier, and Sysmex; Financial Interests, Personal, Invited Speaker: Adacap, Amgen, AstraZeneca, Bayer, Blueprint Medicines, BMS, Boehringer Ingelheim, Celgene, Incyte, Ipsen, Lilly, Merck, MSD, Novartis, PharmaMar, Pfizer, Roche, Sanofi, Servier, and Sysmex; Financial Interests, Personal, Other, board member: Genómica and Altum Sequencing; Financial Interests, Institutional, Research Grant: AstraZeneca, BMS, MSD, and Pfizer. All other authors have declared no conflicts of interest.