10MO - EMPOWER-Lung 1: Cemiplimab (CEMI) monotherapy as first-line (1L) treatment of patients (pts) with brain metastases from advanced non-small cell lung cancer (aNSCLC) with programmed cell death-ligand 1 (PD-L1) ≥50% — 3-year update

Background

In phase III EMPOWER-Lung 1 study, 1L CEMI monotherapy resulted in significantly longer OS and PFS versus chemotherapy (CHEMO) for pts with aNSCLC with no actionable genomic aberrations, whose tumours express PD-L1 ≥50%. The study included pts with treated, clinically stable, baseline brain metastases, a hard-to-treat and underrepresented population in clinical trials. We previously reported improved OS and PFS with 1L CEMI versus CHEMO for this subgroup. In this post hoc analysis, we report 3-year outcomes.

Methods

In EMPOWER-Lung 1, pts were randomised 1:1 to CEMI 350 mg IV Q3W or investigator's choice of CHEMO. The overall median follow-up duration from randomization to data cut-off (4 March 2022) was 37.1 months (mo; range 24.0–56.5). Here, we analyzed pts with treated, clinically stable brain metastases (radiological stability not required).

Results

In all, 69/565 (12.2%) pts with PD-L1 ≥50% had treated, clinically stable brain metastases at randomization. Baseline characteristics in CEMI (n = 34) vs CHEMO (n = 35) groups were: median age, 60.0 (range: 45–76) vs 62.0 (range: 48–77) yrs; male, 97.1% vs 82.9%; and non-squamous histology, 85.3% vs 74.3%. CEMI showed superior efficacy outcomes vs CHEMO: longer median OS (not reached vs 20.7 mo; HR = 0.42, 0.20–0.87), longer median PFS (12.5 vs 5.3 mo; HR = 0.34, 0.18–0.63), a higher ORR (55.9% vs 11.4%) and a longer median duration of response (31.7 mo vs 12.5 mo; table). After baseline, disease progression in brain occurred in 5 (14.7%) pts with CEMI vs 7 (20%) with CHEMO. Incidence of grade ≥3 TEAEs was 35.3% in the CEMI group vs 60.0% in CHEMO.

Data cutoff date 4 March 2022.

Stratified log-rank test P-value.

CI, confidence interval; CR, complete response; ORR, objective response rate; OS, overall survival; mo, months; NA, not applicable; NE, not evaluable; NR, not reached; PFS, progression-free survival; PR, partial response.

Conclusions

Three-year follow up data shows durable clinical benefits and an acceptable safety profile with 1L CEMI monotherapy in subgroup analysis of pts with aNSCLC and brain metastases. CEMI is generally well tolerated in this subgroup.

Clinical trial identification

NCT03088540.

Editorial acknowledgement

Medical writing support was provided by John G Facciponte, PhD, of Prime, Knutsford, UK, funded by Regeneron Pharmaceuticals, Inc. and Sanofi. Responsibility for all opinions, conclusions, and data interpretation lies with the authors.

Legal entity responsible for the study

Regeneron Pharmaceuticals, Inc.

Funding

Regeneron Pharmaceuticals, Inc. and Sanofi.

Disclosure

M. Özgüroğlu: Financial Interests, Personal, Advisory Role, Honoraria: Novartis, Roche, Janssen, Sanofi, Astellas; Financial Interests, Personal, Advisory Board: Janssen, Sanofi, Astellas; Financial Interests, Personal, Other, Travel support: Bristol-Myers Squibb, Janssen, AstraZeneca; Financial Interests, Personal, Invited Speaker: AstraZeneca. A. Sezer: Financial Interests, Institutional, Research Grant: Roche, Merck Sharp & Dohme, Merck Serono, AstraZeneca, Eli Lilly, Novartis, Johnson & Johnson, Regeneron Pharmaceuticals, Inc., Sanofi. M. Gumus: Financial Interests, Institutional, Invited Speaker, Honoraria: Roche, Merck Sharp & Dohme, Gen İlaç, Novartis. I. Cicin: Financial Interests, Personal and Institutional, Advisory Role: Pfizer, Merck Sharp & Dohme Oncology, Roche, Novartis–Ipsen, Eli Lilly, Bristol-Myers Squibb, Servier, Abdi Ibrahim, Nobelpharma, AbbVie, Teva, Janssen Oncology; Financial Interests, Institutional, Invited Speaker, Speaker fees: Novartis, Roche, Bristol-Myers Squibb, Pfizer, Abdi Ibrahim. X. He: Financial Interests, Personal, Full or part-time Employment: Regeneron Pharmaceuticals, Inc.; Financial Interests, Personal, Stocks/Shares: 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.; Financial Interests, Personal, Other, Patents pending: 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.; Financial Interests, Personal, Other, Patents pending: Regeneron Pharmaceuticals, Inc. All other authors have declared no conflicts of interest.