Pembrolizumab in Combination With Platinum-Based Chemotherapy in Patients With Recurrent EGFR and ALK Gene Altered Non-Small-Cell Lung Cancer (NSCLC)

Document Type

Article

Publication Date

3-1-2026

Publication Title

Clinical lung cancer

Keywords

Humans, Carcinoma, Non-Small-Cell Lung, Male, Lung Neoplasms, Female, Antibodies, Monoclonal, Humanized, Anaplastic Lymphoma Kinase, Middle Aged, ErbB Receptors, Antineoplastic Combined Chemotherapy Protocols, Aged, Adult, Carboplatin, Pemetrexed, Neoplasm Recurrence, Local, Mutation, Follow-Up Studies

Abstract

INTRODUCTION: Immune checkpoint inhibitors have limited efficacy in patients with EGFR-mutant (EGFR+) and ALK-rearranged (ALK+) non-small cell lung cancer (NSCLC). We conducted a phase II study to evaluate the efficacy of pembrolizumab with carboplatin and pemetrexed in these patients.

PATIENTS AND METHODS: EGFR+ or ALK+ NSCLC patients, previously treated with targeted therapy, were eligible. Carboplatin, pemetrexed and pembrolizumab were administered every 3 weeks for 4 cycles followed by maintenance pemetrexed and pembrolizumab. The primary endpoint was response rate (RR). Blood for circulating tumor cells (CTCs) was collected prior to the 1st and 3rd cycles. The plan was to enroll 28 evaluable patients in both EGFR+ and ALK+ cohorts.

RESULTS: Of the 33 patients enrolled, 26 had EGFR+ and 7 had ALK+ NSCLC. RR (95% CI,) was 46% (27%, 67%) in EGFR+ and 29% (4%, 71%), in ALK+ patients, respectively. Median progression free survival (PFS) and overall survival (OS) in the EGFR+ cohort were 8.3 months (7.2-16.5) and 22.2 months (20.6-NE), respectively. In the ALK+ cohort, median PFS and OS were both 2.9 months. The median CTC count at baseline in 15 evaluable EGFR+ patients was 4 cells/mL (0-23). OS among EGFR+ patients with decreasing vs. increasing CTC count during treatment was not reached vs. 18.5 months, respectively (P = .52). The most common adverse events were fatigue, nausea, anemia and AST/ALT elevation.

CONCLUSION: Pembrolizumab in combination with chemotherapy demonstrated encouraging RR of 42% and OS of 22 months among patients with recurrent EGFR+ NSCLC. The efficacy in ALK+ patients was not encouraging.

Medical Subject Headings

Humans; Carcinoma, Non-Small-Cell Lung; Male; Lung Neoplasms; Female; Antibodies, Monoclonal, Humanized; Anaplastic Lymphoma Kinase; Middle Aged; ErbB Receptors; Antineoplastic Combined Chemotherapy Protocols; Aged; Adult; Carboplatin; Pemetrexed; Neoplasm Recurrence, Local; Mutation; Follow-Up Studies

PubMed ID

41046186

Volume

27

Issue

2

First Page

189

Last Page

196

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