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Pembrolizumab lacks efficacy, may be unsafe in NSCLC subgroup

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Aaron Elliott Lisberg

CHICAGO — Pembrolizumab failed to demonstrate efficacy in patients with PD-L1-positive, EGFR-mutated advanced non-small cell lung cancer who had not been treated with tyrosine kinase inhibitors and was associated with adverse events that researchers at ASCO called “particularly concerning.”

According to Aaron Elliott Lisberg, MD, of the David Geffen School of Medicine at the University of California, Los Angeles, and colleagues, previous findings from the KEYNOTE-001 trial indicated that patients with EGFR mutations and no history of TKI therapy who were treated at a single center had superior outcomes after receiving pembrolizumab (Keytruda, Merck) compared with patients who received TKI therapy prior to pembrolizumab. Other pembrolizumab studies, however, have generally excluded TKI-naive patients with EGFR mutations, according to Lisberg.

“Data to guide treatment decisions in this patient population are lacking, particularly in patients with PD-L1 expression of 50% or greater.” he told HemOnc Today.

To further investigate the safety and efficacy of pembrolizumab in this population, Lisberg and colleagues conducted an open-label trial assessing 200 mg of pembrolizumab administered every 3 weeks to patients with PD-L1-positive, EGFR-mutated advanced NSCLC. The primary outcome was objective response rate.

The researchers planned on enrolling 25 patients. However, enrollment was terminated early after a lack of efficacy was observed in 11 patients. Only one patient demonstrated an ORR, but further analysis of the patient’s tumor revealed that the original report of an EGFR mutation was inaccurate, according to Lisberg and colleagues.

Most of the 11 patients who received pembrolizumab were women (63.6%) with no history of TKI therapy (81.8%) or smoking (54.6%) who had a PD-LI expression of 50% or greater (72.7%) and non-squamous histology (90.9%).

Although the small number of patients included in the study “precludes definitive conclusions” on the safety profile of pembrolizumab in this population, the researchers highlighted three treatment-related adverse events “of concern,” including grade 3 transaminitis, grade 2 adrenal insufficiency and erlotinib-related pneumonitis. The researchers noted that the case of pneumonitis related to erlotinib (Tarceva, Genentech) may have been triggered by prior pembrolizumab use.

Two deaths — one of which occurred in the patient with pneumonitis — were reported within 6 months of enrollment and were also of concern, according to the researchers.

“Our trial demonstrated a lack of efficacy of pembrolizumab in TKI-naive, PD-L1-positive, EGFR-mutant patients with advanced NSCLC, including those with PD-L1 expression of 50% or greater, suggesting that it is not an appropriate therapeutic choice in this setting,” Lisberg said. – by Stephanie Viguers

Reference:

Lisberg AE, et al. Abstract 9014. Presented at: ASCO Annual Meeting; June 1-5, 2018; Chicago.

Disclosures: Lisberg reports receiving consulting or advisory fees from AstraZeneca.