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Tumor Mutation Burden in Metastatic NSCLC: Predictive of Response to Pembrolizumab?

By: Sarah Campen, PharmD
Posted: Monday, March 23, 2020

For patients with metastatic non–small cell lung cancer (NSCLC), a higher baseline tumor mutation burden may be predictive of response to first-line pembrolizumab-based therapy, according to the results of a study published in Clinical Cancer Research. “Lack of biomarkers beyond the current standard of tissue PD-L1 has limited our ability to select patients who benefit most from immunotherapy,” explained Charu Aggarwal, MD, MPH, of the University of Pennsylvania Perelman School of Medicine, Philadelphia, and colleagues. “[Tumor mutation burden] is a promising biomarker.”

“We believe this is the largest study to show [a] correlation between blood-based tumor mutational burden and clinical outcomes after first-line PD-1–based treatment, including combination chemo-immunotherapy, for NSCLC,” said the study’s senior author Erica L. Carpenter, MBA, PhD, Director of the Liquid Biopsy Laboratory at the University of Pennsylvania, in Penn Medicine press release.

The study enrolled 66 patients with newly diagnosed metastatic NSCLC starting first-line pembrolizumab-based therapy, either alone or in combination with chemotherapy. The researchers assessed the plasma-based tumor mutation burden using a 500-gene next-generation sequencing panel. A total of 52 patients (78.8%) were able to be evaluated.

The plasma-based tumor mutation burden was significantly higher for patients who achieved a durable clinical benefit compared with those who achieved no benefit (21.3 vs. 12.4 mutations per megabase [mut/Mb], P = .003). In patients with a tumor mutation burden of at least 16 mut/Mb, progression-free survival was higher than in those with a tumor mutation burden less than 16 mut/Mb, at 14.1 versus 4.7 months, respectively (P < .001). The researchers also found that several types of mutations, including ERBB2 exon 20, STK11, KEAP1, and PTEN, appear to be negative predictor mutations; that is, patients with a high plasma mutation burden and one or more of these mutations are unlikely to respond to pembrolizumab therapy.

Disclosure: The study authors reported no conflicts of interest.



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