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Clinical Trial
. 2025 May 15;131(10):e35864.
doi: 10.1002/cncr.35864.

Cemiplimab monotherapy as first-line treatment of patients with brain metastases from advanced non-small cell lung cancer with programmed cell death-ligand 1 ≥50

Saadettin Kilickap  1 , Mustafa Özgüroğlu  2 , Ahmet Sezer  3 , Mahmut Gümüş  4 , Igor Bondarenko  5 , Miranda Gogishvili  6 , Haci M Turk  7 , Irfan Cicin  8 , Dmitry Bentsion  9 , Oleg Gladkov  10 , Virote Sriuranpong  11 , Ruben G W Quek  12 , Debra A G McIntyre  12 , Xuanyao He  12 , Jennifer McGinniss  12 , Frank Seebach  12 , Giuseppe Gullo  12 , Petra Rietschel  12 , Jean-Francois Pouliot  12
Affiliations
Clinical Trial

Cemiplimab monotherapy as first-line treatment of patients with brain metastases from advanced non-small cell lung cancer with programmed cell death-ligand 1 ≥50

Saadettin Kilickap et al. Cancer. .

Abstract

Background: In the phase 3 EMPOWER-Lung 1 study, first-line cemiplimab monotherapy provided significant survival benefit versus chemotherapy in patients with advanced non-small cell lung cancer (NSCLC) with programmed cell death-ligand 1 (PD-L1) ≥50%. This exploratory subgroup analysis investigated the clinical outcomes of cemiplimab treatment in patients with advanced NSCLC with brain metastases.

Methods: Patients with advanced NSCLC were randomized (1:1) to cemiplimab 350 mg every 3 weeks or four cycles of platinum doublet chemotherapy (NCT03088540). Patients with symptomatic radiotherapy-treated brain metastases were eligible to enroll. Of the 565 patients with confirmed PD-L1 expression ≥50%, 69 (12%) had brain metastases at baseline.

Results: Patients with brain metastases who received cemiplimab had a median overall survival (OS) of 52.4 months compared with 20.7 months for those who received chemotherapy (hazard ratio [HR], 0.40; p = .0031) and a median progression-free survival (PFS) of 12.5 versus 5.3 months (HR, 0.33; p = .0002), respectively. Patients without brain metastases had a median OS of 24.3 months with cemiplimab versus 12.5 months with chemotherapy (HR, 0.63; p < .0001); their median PFS was 6.5 months versus 5.2 months (HR, 0.55; p < .0001), respectively. Cemiplimab was associated with a significant improvement in global health status/quality of life in all patients, including those with brain metastases. The cemiplimab safety profile was generally similar in all patients.

Conclusions: In patients with advanced NSCLC with PD-L1 ≥50%, first-line cemiplimab monotherapy improved survival and patient-reported outcomes over chemotherapy for those who received prior radiotherapy for symptomatic brain metastases.

Keywords: PD‐L1; advanced NSCLC; brain metastases; cemiplimab; immunotherapy.

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Conflict of interest statement

Virote Sriuranpong reports fees for professional activities from Amgen, AstraZeneca, Daiichi Sankyo Company Ltd, Eisai, F. Hofmann‐La Roche, Merck Sharp & Dohme, Novartis, and Pfizer. Haci M. Turk reports fees for professional activities from Regeneron Pharmaceuticals. Saadettin Kilickap reports travels funding from Regeneron Pharmaceuticals. Mustafa Özgüroğlu reports honoraria from Novartis, Roche, Janssen, Sanofi, and Astellas; advisory board fees from Janssen, Sanofi, and Astellas; travel support from Bristol‐Myers Squibb, Janssen, AstraZeneca, and Regeneron Pharmaceuticals, Inc.; and speaker support from AstraZeneca. Ahmet Sezer reports institutional research support from Roche, Merck Sharp & Dohme, Merck Serono, AstraZeneca, Lilly, Novartis, Johnson & Johnson, Regeneron Pharmaceuticals, Inc., and Sanofi outside the submitted work. Mahmut Gümüş reports honoraria to institution for lectures from Roche, Merck Sharp & Dohme, Gen İlaç, and Novartis outside the submitted work. Irfan Cicin reports personal fees (paid to institution) from Pfizer, Merck Sharp & Dohme Oncology, Roche, Novartis‐Ipsen, Eli Lilly, Bristol‐Myers Squibb, Servier, Abdi Ibrahim, Nobelpharma, AbbVie, Teva, and Janssen Oncology; and speaker’s bureau fees (paid to institution) from Novartis, Roche, Bristol‐Myers Squibb, Pfizer, and Abdi Ibrahim. Ruben G. W. Quek is a shareholder of Regeneron Pharmaceuticals, Inc. Jennifer McGinniss is a shareholder of Regeneron Pharmaceuticals, Inc. Jean‐Francois Pouliot is a shareholder of Regeneron Pharmaceuticals, Inc. Frank Seebach is a shareholder of Regeneron Pharmaceuticals, Inc. Giuseppe Gullo is a shareholder of Regeneron Pharmaceuticals, Inc. Debra A. G. McIntyre is a shareholder of Regeneron Pharmaceuticals, Inc. Xuanyao He is a shareholder of Regeneron Pharmaceuticals, Inc. Petra Rietschel is a shareholder of Regeneron Pharmaceuticals, Inc. The other authors declare no conflicts of interest.

Figures

FIGURE 1
FIGURE 1
Kaplan–Meier curves showing OS by the independent review committee in patients (A) with and (B) without brain metastases at baseline. Patients were stratified by tumor histology, with HR based on a stratified Cox regression model using the treatment as a covariate and tumor histology as a stratification factor. p values are two‐sided. CI indicates confidence interval; HR, hazard ratio; mOS, median overall survival; NE, not evaluable; OS, overall survival.
FIGURE 2
FIGURE 2
Kaplan–Meier curves showing PFS by the independent review committee in patients (A) with and (B) without brain metastases at baseline. Patients were stratified by tumor histology, with HR based on a stratified Cox regression model using the treatment as a covariate and tumor histology as a stratification factor. p values are two‐sided. CI indicates confidence interval; HR, hazard ratio; NE, not evaluable; mPFS, median progression‐free survival; PFS, progression‐free survival.
FIGURE 3
FIGURE 3
Forest plot model of estimated between‐treatment differences (cemiplimab vs. chemotherapy) in overall change from baseline (MMRM model) in patients with brain metastases at baseline per (A) EORTC QLQ‐C30 GHS/QoL and functional scales, (B) EORTC QLQ‐C30 symptom scales, and (C) EORTC QLQ‐LC13 symptom scales. CI indicates confidence interval; EORTC, European Organization for Research and Treatment of Cancer; GHS, global health status; LC, lung cancer; LS, least‐squares; MMRM, mixed‐model with repeated measures; QLQ‐C30, Quality of Life‐Core 30; QLQ‐LC13, Quality of Life‐Lung Cancer Module; QoL, quality of life; SE, standard error.
See this image and copyright information in PMC

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