Pembrolizumab (pembro) + carboplatin and paclitaxel/nab-paclitaxel significantly improved OS and PFS vs placebo in patients (pts) with previously untreated stage IV squamous NSCLC in the phase III KEYNOTE-407 study (NCT02775435). At protocol-specified final analysis (data cutoff May 9, 2019), HR for OS was 0.71 (95% CI, 0.58–0.88). We report long-term data and outcomes for pts who completed 35 cycles (∼2 y) of treatment.
Eligible pts were randomized 1:1 (stratified by paclitaxel vs nab-paclitaxel; East Asia vs rest of the world; and PD-L1 TPS ≥1% vs <1%) to receive pembro 200 mg + chemo or placebo + chemo Q3W for 4 cycles, then pembro or placebo for up to a total of 35 cycles. Primary endpoints were OS and PFS per RECIST v1.1 by blinded independent central review.
278 pts were randomized to pembro + chemo and 281 to the placebo + chemo group. As of Sep 30, 2020, median time from randomization to data cutoff was 40.1 (range, 33.1–49.4) mo; 117 (41.6%) pts crossed over from the placebo + chemo group to receive pembro monotherapy. Median OS in the pembro + chemo group was 17.2 vs 11.6 mo for placebo + chemo; HR 0.71 (95% CI, 0.59–0.86). 3-year OS rate was 29.7% vs 18.2%, respectively. Median PFS2 was 13.8 vs 9.1 mo, respectively; HR 0.59 (95% CI, 0.49–0.71;
| Pembro + Chemo (n = 278) | Placebo + Chemo (n = 281) | |
|---|---|---|
| Median OS, mo (95% CI) | 17.2 (14.4–19.7) | 11.6 (10.1–13.7) |
| OS HR (95% CI) | 0.71 (0.59–0.86) | |
| 3-y OS rate, % (95% CI) | 29.7 (24.5–35.2) | 18.2 (13.8–23.0) |
| Median PFS, mo (95% CI) | 8.0 (6.3–8.5) | 5.1 (4.3–6.0) |
| PFS HR (95% CI) | 0.59 (0.49–0.71) | |
| 3-y PFS rate, % (95% CI) | 16.1 (12.0–20.8) | 6.5 (3.9–10.0) |
| Median PFS2,a mo (95% CI) | 13.8 (12.2–15.9) | 9.1 (8.0–10.3) |
| PFS2 HR (95% CI) | 0.59 (0.49–0.71) | |
| ORR, % (95% CI) | 62.6 (56.6–68.3) | 38.8 (33.1–44.8) |
| Median DOR, mo (range) | 9.0 (1.3+ to 45.0+) | 4.9 (1.3+ to 44.8+) |
+, indicates no PD at last disease assessment. aTime from randomization to second/subsequent PD on next-line treatment/death.
With ∼3 y of follow-up, pembro + chemo continued to demonstrate durable benefit vs chemo alone without additional toxicity. Most pts who completed 35 cycles had objective responses and were alive at data cutoff. These data continue to support pembro + chemo as first-line treatment in pts with metastatic squamous NSCLC.
NCT02775435.
Writing support was provided by Kathleen Estes, PhD, of ICON plc (North Wales, PA, USA), 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.
A.G. Robinson: Research grant/Funding (institution): AstraZeneca; Research grant/Funding (institution): Merck; Advisory/Consultancy, Research grant/Funding (institution): Pfizer; Research grant/Funding (institution): Roche. D. Vicente: Honoraria (self), honoraria to self/spouse for scientific advice or as a speaker: AstraZeneca; Honoraria (self), honoraria to self/spouse for scientific advice or as a speaker: BMS; Honoraria (self), honoraria to self/spouse for scientific advice or as a speaker: Boehringer Ingelheim; Honoraria (self), honoraria to self/spouse for scientific advice or as a speaker: MSD; Honoraria (self), honoraria to self/spouse for scientific advice or as a speaker: Pfizer; Honoraria (self), honoraria to self/spouse for scientific advice or as a speaker: Roche. A. Tafreshi: Research grant/Funding (institution), received funding to their institutions from Merck to support study conduct: Merck. H. Soto Parra: Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: BMS; Advisory/Consultancy: Eli Lilly; Advisory/Consultancy: MSD; Advisory/Consultancy: Roche. J. Mazieres: Honoraria (self), Research grant/Funding (institution): AstraZeneca; Honoraria (self): Bayer; Honoraria (self): Blueprint; Honoraria (self), Research grant/Funding (institution): BMS; Honoraria (self): Boehringer Ingelheim; Honoraria (self): Merck; Honoraria (self), Research grant/Funding (institution): MSD; Honoraria (self): Pfizer; Honoraria (self): PharmaMar; Honoraria (self): Pierre Fabre; Honoraria (self), Research grant/Funding (institution): Roche. I. Cicin: Advisory/Consultancy, Research grant/Funding (institution): AstraZeneca; Advisory/Consultancy, Research grant/Funding (institution): Boehringer Ingelheim; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Eli Lilly; Advisory/Consultancy: F. Hoffmann-La Roche; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: MSD; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Pfizer; Travel/Accommodation/Expenses: Novartis; Research grant/Funding (institution), Travel/Accommodation/Expenses: Quintiles; Travel/Accommodation/Expenses: Roche; Research grant/Funding (institution): Astellas; Research grant/Funding (institution): BMS; Research grant/Funding (institution): Merck Serono; Research grant/Funding (institution): Parexel; Research grant/Funding (institution): Taiho. B. Medgyasszay: Honoraria (self), Research grant/Funding (institution): Merck; Honoraria (self), Research grant/Funding (institution): BMS; Honoraria (self), Research grant/Funding (institution): AstraZeneca; Honoraria (self), Research grant/Funding (institution): Eli Lilly; Honoraria (self), Research grant/Funding (institution): Novartis; Research grant/Funding (institution): Astellas; Research grant/Funding (institution): Boehringer Ingelheim; Research grant/Funding (institution): Eli Lilly; Research grant/Funding (institution): MSD; Research grant/Funding (institution): Parexel; Research grant/Funding (institution): Quintiles; Research grant/Funding (institution): Taiho. J. Rodríguez-Cid: Research grant/Funding (institution): MSD; Research grant/Funding (institution): Bayer; Research grant/Funding (institution): BMS; Research grant/Funding (institution): Celgene; Research grant/Funding (institution): Eli Lilly; Research grant/Funding (institution): MSD; Research grant/Funding (institution): Roche; Research grant/Funding (institution): Novartis. I. Okamoto: Honoraria (self), Research grant/Funding (self): AstraZeneca; Honoraria (self), Research grant/Funding (self): BMS; Honoraria (self), Research grant/Funding (self): Boehringer Ingelheim; Honoraria (self), Research grant/Funding (self): Chugai Pharma; Honoraria (self), Research grant/Funding (self): Eli Lilly; Honoraria (self), Research grant/Funding (self): MSD Oncology; Honoraria (self), Research grant/Funding (self): Ono Pharmaceutical; Honoraria (self), Research grant/Funding (self): Taiho; Honoraria (self): Pfizer; Research grant/Funding (self): AbbVie; Research grant/Funding (self): Astellas Pharma; Research grant/Funding (self): Novartis. S. Lee: Research grant/Funding (institution), received funding to their institutions from Merck to support study conduct: Merck. R. Ramlau: Honoraria (self), received honoraria to self/spouse for scientific advice or as a speaker: Amgen; Honoraria (self), Leadership role, received honoraria to self/spouse for scientific advice or as a speaker: AstraZeneca; Honoraria (self), Leadership role, received honoraria to self/spouse for scientific advice or as a speaker: BMS; Honoraria (self), Leadership role, received honoraria to self/spouse for scientific advice or as a speaker: Boehringer Ingelheim; Honoraria (self), Leadership role, received honoraria to self/spouse for scientific advice or as a speaker: Eli Lilly; Honoraria (self), received honoraria to self/spouse for scientific advice or as a speaker: Merck; Honoraria (self), Leadership role, received honoraria to self/spouse for scientific advice or as a speaker: MSD; Honoraria (self), Leadership role, received honoraria to self/spouse for scientific advice or as a speaker: Novartis; Honoraria (self), Leadership role, received honoraria to self/spouse for scientific advice or as a speaker: Pfizer; Honoraria (self), Leadership role, received honoraria to self/spouse for scientific advice or as a speaker: Roche; Honoraria (self), received honoraria to self/spouse for scientific advice or as a speaker: Sanofi; Leadership role, Board member: AbbVie; Leadership role, Board member: Takeda. V. Vladimirov: Research grant/Funding (institution), received funding to their institutions from Merck to support study conduct: Merck. Y. Cheng: Research grant/Funding (institution), received funding to their institutions from Merck to support study conduct: Merck. B. Halmos: Research grant/Funding (institution): AbbVie; Advisory/Consultancy, Research grant/Funding (institution): AstraZeneca; Advisory/Consultancy, Research grant/Funding (institution): BMS; Advisory/Consultancy, Research grant/Funding (institution): Boehringer Ingelheim; Research grant/Funding (institution): Eli Lilly; Research grant/Funding (institution): GSK; Advisory/Consultancy, Research grant/Funding (institution): Guardant Health; Advisory/Consultancy, Research grant/Funding (institution): Merck; Research grant/Funding (institution): Mirati; Advisory/Consultancy, Research grant/Funding (institution): Novartis; Advisory/Consultancy, Research grant/Funding (institution): Pfizer; Research grant/Funding (institution): Takeda; Advisory/Consultancy: Genentech; Advisory/Consultancy: Genentech. C-C. Liu: Full/Part-time employment: Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. P. Schwarzenberger: 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. L. Paz-Ares: Honoraria (self): Amgen, AstraZeneca, Bayer, Blueprint Medicines, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Eli Lilly, Ipsen, Merck, Merck Sharp and Dohme, Mirati, Novartis, Pfizer, Pharmamar, Roche, Sanofi, Servier, Sysmex, Takeda; Speaker Bureau/Expert testimony: Roche, Lilly, AstraZeneca, MSD, BMS; Leadership role: Altum Sequencing; Research grant/Funding (self): AstraZeneca, Bristol-Myers Squibb, Merck Sharp and Dohme; Officer/Board of Directors: Genómica; Spouse/Financial dependant: AAA, Advanz Pharma, Bayer, HMP, Ipsen, Merck, Midatech Pharma, MSD, Novartis, PharmaMar, Pfizer, Pierre Fabre, Roche, Servier and Sanofi.