Pembrolizumab shows potential in TKI-resistant EGFR+ NSCLC, not ALK+

A small study demonstrated a response rate of 42%, a median progression-free survival (PFS) of 8.3 months, and a median overall survival of 22.2 months in patients with recurrent epithelial growth factor receptor (EGFR)+ non-small-cell lung cancer (NSCLC) treated with pembrolizumab plus carboplatin and pemetrexed [1].

For patients with either EGFR or anaplastic lymphoma kinase (ALK)+ NSCLC, guidelines recommend treatment with targeted tyrosine kinase inhibitors (TKIs). Current PFS periods with targeted therapy range from 10–19 months in patients with EGFR+ NSCLC and 10–34 months in patients with ALK+ NSCLC. However, there is a need for treatment options for TKI-refractory EGFR/ALK+ NSCLC. Most commonly, platinum-based chemotherapy is implemented following TKI therapy, eliciting a response rate of 30% and affording 4–5 months of PFS.

Investigators of a phase 2 trial (NCT03242915) hypothesised that the addition of pembrolizumab would enhance the efficacy of a carboplatin and pemetrexed protocol in TKI-refractory EGFR or ALK+ NSCLC.  Of the 33 patients with NSCLC enrolled, 26 had EGFR mutations and 7 had ALK rearrangements. All patients completed 4 cycles of carboplatin (AUC5 every 3 weeks) and pemetrexed (500 mg/m2 intravenously on day 1 of each 3-week cycle) plus pembrolizumab (200mg intravenously every 3 weeks), followed by maintenance treatment with pemetrexed and pembrolizumab for 2 years.

Prof. Shirish Gadgeel (University of Michigan, USA) presented the 1-year follow-up results. The primary outcome measure -response rate within 12 months- was 42.3% in the EGFR+ cohort and 28.6% in the ALK+ cohort (deemed limited activity).

Secondary outcome measures were PFS and overall survival at 12 months. The median PFS was 8.3 months in the EGFR+ cohort and 2.9 months in the ALK+ cohort. The median overall survival was 22.2 months in the EGFR+ cohort and 2.9 months in the ALK+ cohort.

No unexpected adverse events occurred in the cohorts; the most common adverse events were fatigue, gastrointestinal symptoms, and cytopaenia.

The investigators concluded that these results warrant further evaluation of treatment with pembrolizumab plus chemotherapy in patients with recurrent EGFR+ NSCLC.

1. Gadgeel S. Pembrolizumab in combination with platinum-based chemotherapy in recurrent EGFR/ALK-positive non-small lung cancer (NSCLC). OA 09.03, WCLC 2021, 8–14 September.

 

Copyright ©2021 Medicom Medical Publishers



Posted on 21 September 202129 February 2024