Pembrolizumab (pembro) + chemotherapy (chemo) in metastatic squamous NSCLC: Final analysis and progression after the next line of therapy (PFS2) in KEYNOTE-407
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. 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. 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. LBA82 LBA82 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. NCT02775435. 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. Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. 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...