4134 - Pembrolizumab (pembro) + chemotherapy (chemo) in metastatic squamous NSCLC: final analysis and progression after the next line of therapy (PFS2) in KEYNOTE-407

Background

In the randomized KEYNOTE-407 study (NCT02775435), pembro + carboplatin and paclitaxel/nab-paclitaxel (chemo) significantly improved OS, PFS, and ORR compared with placebo + chemo in patients (pts) with previously untreated metastatic squamous NSCLC. Benefit was observed irrespective of PD-L1 TPS. We report updated OS from the protocol-specified final analysis and, for the first time, PFS2.

Methods

Eligible pts were randomized 1:1 to pembro (n = 278) or placebo (n = 281) + 4 cycles of carboplatin and paclitaxel/nab-paclitaxel. Randomization was stratified by PD-L1 TPS (≥1%/<1%), choice of taxane (paclitaxel/nab-paclitaxel), and region (East Asia/rest of world). Pts in the placebo + chemo arm could crossover to pembro monotherapy at the time of confirmed PD. After positive results from IA2, pts on the placebo arm were unblinded to stop placebo. Response was assessed by RECIST v1.1 by blinded central review. Primary endpoints were OS and PFS. PFS2 was an exploratory endpoint and defined as time from randomization to time of PD per investigator or death after start of 2L therapy, whichever occurred first.

Results

With median follow-up of 14.3 mo (range, 0.1–31.3) and 365 total deaths, pembro + chemo continued to improve OS (median [95% CI], 17.1 [14.4–19.9] vs 11.6 [10.1–13.7] mo), PFS (median [95% CI], 8.0 [6.3–8.4] vs 5.1 [4.3–6.0]; Table) and ORR (62.6% vs 38.4%). 2L+ therapy was received by 32.0% in the pembro + chemo arm and 59.4% (49.1% 2L+ antiPD[L]1) in the placebo + chemo arm. PFS2 was longer for 1L pembro + chemo (median [95% CI], 13.8 [12.2–15.9] mo vs 9.1 [8.2–10.2] mo), with no difference by PD-L1 TPS.Table:

LBA82

Conclusions

Pembro + chemo continued to demonstrate improved outcomes, including OS, PFS, ORR and PFS2, compared with placebo + chemo for previously untreated metastatic squamous NSCLC, with a manageable safety profile. These results support first-line pembro + chemo in pts with metastatic squamous NSCLC.

Clinical trial identification

NCT02775435.

Editorial acknowledgement

Writing support was provided by Sheri Arndt, PharmD, of C4 MedSolutions, LLC (Yardley, PA, USA), a CHC Group company, funded by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.

Legal entity responsible for the study

Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA

Funding

Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.

Disclosure

L. Paz-Ares: Honoraria (self), Spouse / Financial dependant, honoraria to self/spouse for scientific advice or as a speaker: Roche; Honoraria (self), Spouse / Financial dependant, honoraria to self/spouse for scientific advice or as a speaker: Lilly; Honoraria (self), Spouse / Financial dependant, honoraria to self/spouse for scientific advice or as a speaker: Boehringer Ingelheim; Honoraria (self), Spouse / Financial dependant, honoraria to self/spouse for scientific advice or as a speaker: AstraZeneca; Honoraria (self), Spouse / Financial dependant, honoraria to self/spouse for scientific advice or as a speaker: Novartis; Honoraria (self), Spouse / Financial dependant, honoraria to self/spouse for scientific advice or as a speaker: Pfizer; Honoraria (self), Spouse / Financial dependant, honoraria to self/spouse for scientific advice or as a speaker: Amgen; Honoraria (self), Spouse / Financial dependant, honoraria to self/spouse for scientific advice or as a speaker: BMS; Honoraria (self), Spouse / Financial dependant, honoraria to self/spouse for scientific advice or as a speaker: MSD; Honoraria (self), Spouse / Financial dependant, honoraria to self/spouse for scientific advice or as a speaker: Merck; Honoraria (self), Spouse / Financial dependant, honoraria to self/spouse for scientific advice or as a speaker: Sanofi; Honoraria (self), Spouse / Financial dependant, honoraria to self/spouse for scientific advice or as a speaker: PharmaMar; Honoraria (self), Spouse / Financial dependant, honoraria to self/spouse for scientific advice or as a speaker: Servier; Honoraria (self), Spouse / Financial dependant, honoraria to self/spouse for scientific advice or as a speaker: Sysmex; Honoraria (self), Spouse / Financial dependant, honoraria to self/spouse for scientific advice or as a speaker: Incyte; Honoraria (self), Spouse / Financial dependant, honoraria to self/spouse for scientific advice or as a speaker: Ipsen; Honoraria (self), Spouse / Financial dependant, honoraria to self/spouse for scientific advice or as a speaker: Adacap; Honoraria (self), Spouse / Financial dependant, honoraria to self/spouse for scientific advice or as a speaker: Bayer; Honoraria (self), Spouse / Financial dependant, honoraria to self/spouse for scientific advice or as a speaker: Blueprint Medicines; Honoraria (self), Spouse / Financial dependant, honoraria to self/spouse for scientific advice or as a speaker: Celgene; Honoraria to self/spouse for scientific advice or as a speaker for Roche, Lilly, Boehringer Ingelheim, AstraZeneca, Novartis, Pfizer, Amgen, BMS, MSD, Merck, Sanofi, PharmaMar, Servier, Sysmex, Incyte, Ipsen, Adacap, Bayer, Blueprint Medicines, and Celgene; board member for Genómica; grants to institution from MSD, BMS, AstraZeneca, and Pfizer. D. Vicente: Honoraria (self), Self/spouse for scientific advice or as a speaker: Boehringer Ingelheim, AstraZeneca, Pfizer, BMS, and MSD . A. Robinson: Research grant / Funding (institution), funding for clinical trials: Merck, AstraZeneca, Roche, and Pfizer; Advisory / Consultancy: Merck. H. Soto Parra: Advisory / Consultancy: AstraZeneca, MSD, BMS, Roche, and Eli Lilly. J. Mazières: Honoraria (institution): Roche, AstraZeneca, Boehringer Ingelheim, Pfizer, BMS, MSD, Merck, Pierre Fabre, PharmaMar, Bayer, and Blueprint; Research grant / Funding (institution): Roche, MSD, BMS, and AstraZeneca. B. Hermes: Travel / Accommodation / Expenses: PharmaMar and Eli Lilly; Honoraria (institution), honoraria for lectures: BMS and Pfizer; Research grant / Funding (institution): MSD, Novartis, BMS, Bayer, Roche, Eli Lilly, and PharmaMar. I. Cicin: Advisory / Consultancy: AstraZeneca, Boehringer Ingelheim, Eli Lilly, MSD, F. Hoffmann-La Roche, and Pfizer; Research grant / Funding (self), personal fees for lectures: Eli Lilly, MSD, Novartis, Pfizer, Quintiles, and Roche; Research grant / Funding (institution), funding to the institution to support trial conduct: Astellas, AstraZeneca, Boehringer Ingelheim, BMS, Eli Lilly, MSD, Parexel, Pfizer, Quintiles, Taiho, and Merck Serono. J. Rodríguez Cid: Research grant / Funding (institution), funding to the institution during conduct of this trial: MSD; Research grant / Funding (institution), funding to the institution to support trial conduct: Bayer, BMS, Celgene, Eli Lilly, MSD, Novartis, and Roche. I. Okamoto: Research grant / Funding (self), grants and personal fees: AstraZeneca, Taiho Pharmaceutical, Boehringer Ingelheim, Ono Pharmaceutical, MSD Oncology, Eli Lilly, BMS, Chugai Pharma; Research grant / Funding (self), personal fees : Pfizer; Research grant / Funding (institution), grants: Astellas Pharma, Novartis, and AbbVie. R. Ramlau: Honoraria (self), honoraria to self/spouse for scientific advice or as a speaker: Roche, Eli Lilly, Boehringer Ingelheim, AstraZeneca, Novartis, Pfizer, Amgen, BMS, MSD, Merck, and Sanofi; Officer / Board of Directors, board member: Boehringer Ingelheim, Pfizer, MSD, BMS, Novartis, Takeda, AbbVie, AstraZeneca, Eli Lilly, and Roche. X. Deng: Full / Part-time employment: Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.. T. Bas: Full / Part-time employment: Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.. B. Piperdi: Full / Part-time employment: Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.. B. Halmos: Research grant / Funding (institution): Merck, BMS, Boehringer Ingelheim, Eli Lilly, Novartis, GSK, Pfizer, AbbVie, AstraZeneca, Mirati, Takeda, and Guardant Health; Advisory / Consultancy, consultant : Merck, Novartis, Boehringer Ingelheim, AstraZeneca, Novartis, Pfizer, Guardant Health, Spectrum, BMS, and Genentech. All other authors have declared no conflicts of interest.