Liquid biopsy to predict clinical response to immunotherapy in metastatic non-small cell lung cancer?

Written by Alex Hyde, Future Science Group

Scientists from Perelman School of Medicine (University of Pennsylvania, PA, USA) and the Abramson Cancer Center (PA, USA) have reported a liquid biopsy panel to measure the quantity of tumor mutations in the blood of individuals with non-small cell lung cancer (NSCLC). Findings of the study indicate that a blood test could be used to predict the clinical response to immunotherapy in metastatic NSCLC.

The study, published in Clinical Cancer Research, demonstrated that individuals with NSCLC who have higher quantities of tumor mutations in their blood generally respond better to pembrolizumab-based immunotherapy treatments than patients with a lower quantity of tumor mutations.

NSCLC is the most common form of lung cancer and the 5-year survival rate for individuals with metastatic disease is 6%. Classically, tissue biopsies are analyzed for the presence of the PD-L1, a protein biomarker that can be used to predict the clinical response to immunotherapy with a PD-1 inhibitor. This research aimed address the shortfalls of the tissue-based biomarker PD-L1 by investigating biomarkers in non-invasive blood samples.

Lead author, Charu Aggarwal (University of Pennsylvania), explained: “While some people see a benefit from these therapies, unfortunately not everyone does. There is an important clinical need to identify new, non-invasive 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.”

In the study, researchers screened blood samples for mutations in 500 different genes and developed a liquid biopsy panel to measure the number of detectable mutations in the blood, known as the tumor mutational burden (TMB). In an evaluation of 52 patients, median TMB was significantly higher for individuals who experienced a durable clinical benefit (DCB) – where a DCB is defined as a complete response, partial response or stable disease for greater than 6 months.

Following the identification of the low and high TMB groups, the researchers investigated progression-free survival and overall survival in both groups. The team successfully identified a higher median progression free survival in the 28 patients of the high TMB group.Senior author Erica Carpenter commented: “We believe this is the largest study to show correlation between blood-based tumor mutational burden and clinical outcomes after first-line PD-1-based treatment, including combination chemo-immunotherapy, for NSCLC.”

The research team hope that future research will validate these findings in larger studies.

Sources: Aggarwal C, Thompson JC, Chien AL et al. Baseline plasma tumor mutation burden predicts response to pembrolizumab-based therapy in patients with metastatic non-small cell lung cancer. Clin. Cancer Res. doi:10.1158/1078-0432.CCR-19-3663 (2020)(Epub ahead of print);