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 3 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; Table). Grade 3−5 AEs occurred in 74.8% of pts in the pembro + chemo group and 70.0% in the placebo + chemo group. Among 55 pts who completed 35 cycles of pembro, ORR was 92.7% (5 CR, 46 PR) and 4 pts (7.3%) had SD. 51 pts (92.7%) were alive, and 1-year OS and PFS after completion of 35 cycles were 96.0% and 82.6%. 7 pts had initiated a second course of pembro at data cutoff.
| Table. Efficacy Outcomes in the ITT Population | ||
|---|---|---|
| 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.
ClinicalTrials.gov, 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.