EMPOWER-Lung 3, a randomized, double-blind, placebo-controlled phase III trial, examined cemiplimab (anti-PD-1) plus chemotherapy (chemo) in patients with advanced non-small cell lung cancer (NSCLC) without EGFR, ALK or ROS1 aberrations, with either squamous or non-squamous histology and any level of PD-L1 expression. Previously we reported that, after 16.4 months follow-up, cemiplimab + chemo improved median overall survival (OS) over chemo alone (21.9 vs 13.0 months, HR = 0.71, 0.53–0.93). Here, we report longer-term data after 28.4 months follow-up.
Patients were randomized 2:1 to receive 4 cycles of platinum-doublet chemo, with 350 mg cemiplimab (n = 312) or placebo (n = 154) every 3 weeks for up to 108 weeks. The primary endpoint was OS; secondary endpoints included progression-free survival (PFS) and objective response rates (ORR).
After a median of 28.4 months follow-up, cemiplimab + chemo continued to show significantly improved OS and PFS vs chemo alone. Median OS was 21.1 months for cemiplimab + chemo vs 12.9 months for chemo alone (HR = 0.65, 0.51–0.82, p = 0.0003). Median PFS was 8.2 months for cemiplimab + chemo vs 5.5 months for chemo alone (HR = 0.55, 0.44–0.68, p < 0.0001). ORRs were 43.6% vs 22.1%, with a duration of response of 16.4 and 7.3 months, respectively. Safety profiles for longer-term use of cemiplimab + chemo were generally consistent with previously reported data; Grade ≥3 treatment-emergent adverse events (TEAEs) occurred in 48.7% of patients in cemiplimab + chemo and 32.7% in chemotherapy alone.
| m = Median | Cemiplimab + chemo (N = 312) | Chemo alone (N = 154) |
|---|---|---|
| mDuration of follow-up | 28.3 | 28.7 |
| mOS, months | 21.1 | 12.9 |
| HR (95% CI) | 0.65 (0.51, 0.82); P < 0.0003 | |
| mPFS, months | 8.2 | 5.5 |
| HR (95% CI) | 0.55 (0.44, 0.68); P < 0.0001 | |
| ORR, % | 44% | 22% |
| Odds ratio (95% CI) | 2.82 (1.80-4.41); P < 0.0001 | |
| Complete response, n (%) | 13 (4%) | 0 |
| Partial response, n (%) | 123 (39%) | 34 (22%) |
| Kaplan-Meier estimated mDOR (95% CI), months | 16.4 months | 7.3 months |
| ≥Grade 3 TEAEs | 152 (48.7%) | 50 (32.7%) |
CI, confidence interval; DOR, duration of response; HR, hazard ratio; ORR, objective response rate; OS, overall survival; PFS, progression-free survival; TEAEs, treatment-emergent adverse events.
At 28.4 months of follow-up, the EMPOWER-3 Lung trial continues to show an improvement in benefit of cemiplimab in combination with chemo, compared to chemo alone, for patients with advanced squamous and non-squamous NSCLC, regardless of PD-L1 expression level and without EGFR, ALK or ROS1 aberrations.
NCT03409614.
Medical writing support was provided by Rachel McGrandle, MSc, of Prime, Knutsford, UK, funded by Regeneron Pharmaceuticals, Inc. and Sanofi. Responsibility for all opinions, conclusions, and data interpretation lies with the authors.
Regeneron Pharmaceuticals, Inc.
Regeneron Pharmaceuticals, Inc. and Sanofi.
K.D. Penkov: Financial Interests, Personal, Other, Honoraria: AstraZeneca, Merck Sharp & Dohme, Nektar, Pfizer, Regeneron Pharmaceuticals, Inc., Roche; Financial Interests, Personal, Advisory Role: Nektar. E. Kalinka: Financial Interests, Personal, Other, Honoraria: Amgen, AstraZeneca, Bristol-Myers Squibb, Merck Sharp & Dohme, Nektar, Pfizer, Roche, Regeneron Pharmaceuticals, Inc. S. Li: Financial Interests, Personal, Full or part-time Employment: Regeneron Pharmaceuticals, Inc.; Financial Interests, Personal, Stocks/Shares: Regeneron Pharmaceuticals, Inc. Y. Li: Financial Interests, Personal, Stocks/Shares: Regeneron Pharmaceuticals, Inc.; Financial Interests, Personal, Full or part-time Employment: Regeneron Pharmaceuticals, Inc. M. Kaul: Financial Interests, Personal, Stocks/Shares: Regeneron Pharmaceuticals, Inc.; Financial Interests, Personal, Full or part-time Employment: Regeneron Pharmaceuticals, Inc. J. Pouliot: Financial Interests, Personal, Full or part-time Employment: Regeneron Pharmaceuticals, Inc.; Financial Interests, Personal, Stocks/Shares: Regeneron Pharmaceuticals, Inc. F. Seebach: Financial Interests, Personal, Full or part-time Employment: Regeneron Pharmaceuticals, Inc.; Financial Interests, Personal, Stocks/Shares: Regeneron Pharmaceuticals, Inc. I. Lowy: Financial Interests, Personal, Full or part-time Employment: Regeneron Pharmaceuticals, Inc.; Financial Interests, Personal, Stocks/Shares: Regeneron Pharmaceuticals, Inc. G. Gullo: Financial Interests, Personal, Full or part-time Employment: Regeneron Pharmaceuticals, Inc.; Financial Interests, Personal, Stocks/Shares: Regeneron Pharmaceuticals, Inc. P. Rietschel: Financial Interests, Personal, Full or part-time Employment: Regeneron Pharmaceuticals, Inc.; Financial Interests, Personal, Stocks/Shares: Regeneron Pharmaceuticals, Inc. All other authors have declared no conflicts of interest.