Plasma-Based Tumor Mutational Burden May Predict Response to Immunotherapy in Patients With Metastatic NSCLC
Patients with non–small cell lung cancer (NSCLC) with higher measures of tumor mutations that show up in a blood test generally have a better clinical response to certain immunotherapy treatments than patients with a lower measure of mutations. A clinical trial showed that in cases where liquid biopsy detects higher volumes of mutations, patients with cancers that have spread are more likely to see a clinical benefit with immunotherapy at 6 months, as well as to survive longer without seeing their disease progress. The findings were published by Aggarwal et al in Clinical Cancer Research.
“While some people see a benefit from these therapies, unfortunately not everyone does. There is an important clinical need to identify new, noninvasive biomarkers to help us guide each patient to the treatments that have the best chance of success for them, and our findings show we may now have a tool to help us do that,” said the study’s lead author Charu Aggarwal, MD, MPH, the Leslye M. Heisler Assistant Professor for Lung Cancer Excellence at the Perelman School of Medicine at the University of Pennsylvania.
- Patients who achieved a durable clinical benefit had a median of 21.3 mutations/Mb, compared to 12.4 mutations/Mb in patients who did not achieve a durable clinical benefit.
- The 28 patients with more than 16 detectable mutations/Mb had a median progression-free survival of 14.1 months compared to 4.7 months for the 24 patients in the lower tumor mutational burden group.
- Median overall survival was not reached for the high tumor mutational burden group; the low tumor mutational burden group had a median overall survival of 8.8 months.
With a simple blood draw, researchers can screen for mutations in 500 different genes. They used this liquid biopsy panel to measure the tumor mutational burden of 66 patients, 52 of whom were evaluable for this trial. The median tumor mutational burden was 16.8 mutations per megabase (Mb) and was significantly higher for patients who experienced a durable clinical benefit compared to those who did not. Patients who achieved a durable clinical benefit had a median of 21.3 mutations/Mb, compared to 12.4 mutations/Mb in patients who did not achieve a durable clinical benefit.
The researchers then examined the progression-free survival and overall survival of both groups. The 28 patients with more than 16 detectable mutations/Mb had a median progression-free survival of 14.1 months compared to 4.7 months for the 24 patients in the lower tumor mutational burden group. Median overall survival was not reached for the high tumor mutational burden group. The low tumor mutational burden group had a median overall survival of 8.8 months.
“We believe this is the largest study to show a correlation between blood-based tumor mutational burden and clinical outcomes after first-line [programmed cell death protein 1]-based treatment, including combination chemoimmunotherapy, for NSCLC,” said the study’s senior author Erica L. Carpenter, MBA, PhD, Director of the Liquid Biopsy Laboratory and a Research Assistant Professor of Medicine at Penn.
The researchers say a larger trial is needed to confirm the findings.
Disclosure: This study was supported by the National Cancer Institute, the LUNGevity Foundation, and Merck & Co. For full disclosures of the study authors, visit clincancerres.aacrjournals.org.The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.