Non-Small Cell Lung Cancer Coverage from Every Angle
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Biomarker-Directed Analysis of First-Line Pembrolizumab-Based Therapies in NSCLC

By: Julia Fiederlein
Posted: Thursday, December 23, 2021

Assessments of the T-cell–inflamed gene-expression profile and tumor mutational burden seemed to be feasible and clinically useful in studying the clinical activity of three first-line pembrolizumab-based combination therapies in patients with advanced non–small cell lung cancer (NSCLC), according to the multicenter phase II KEYNOTE-495/KeyImPaCT trial. This interim analysis, which was presented by Martin Gutierrez, MD, of the Hackensack University Medical Center, New Jersey, and colleagues during the 2021 Society for Immunotherapy of Cancer (SITC) Annual Meeting (Abstract 457) and published in the Journal for ImmunoTherapy of Cancer, may shed light on the unique biology of each biomarker subgroup.

“The [subgroup with high T-cell–inflamed gene expression and tumor mutational burden] demonstrated the best response among the biomarker subgroups for all three combination therapies,” the investigators commented. “Further validation is needed to determine additional signals and may be addressed as more mature data become available.”

Patients were allocated to a biomarker-defined subgroup and randomly assigned in a 1:1:1 ratio to receive pembrolizumab plus lenvatinib (n = 72), quavonlimab (n = 72), or favezelimab (200 mg: n = 30; 800 mg: n = 34). In all treatment groups, the objective response rates appeared to be the highest in patients with high T-cell–inflamed gene expression and tumor mutational burden; response rates seemed to be similar across combinations within this biomarker subgroup. On the other hand, in those with low T-cell–inflamed gene expression and tumor mutational burden, the objective response rates seemed to be low across combinations.

A total of 88%, 65%, 57%, and 59% of patients treated with lenvatinib, quavonlimab, and 200 and 800 mg of favezelimab, respectively, experienced treatment-related adverse events. Most treatment-related adverse events were grade 1 or 2; however, this did not seem to hold true in patients treated with lenvatinib (grade 3–5: 63%).

Disclosure: No information regarding conflicts of interest was provided.



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