Liquid Biopsies Improve Delivery of Targeted Therapy in Metastatic NSCLC

New York—The addition of a liquid biopsy to standard care tumor surveillance involving tissue next-generation sequencing (NGS) led to a marked increase in the detection of mutations that can be targeted with therapy in patients with non–small-cell lung cancer (NSCLC), according to results from a study presented at the 23rd Annual Perspectives in Thoracic Oncology meeting.

“The data so far suggest that not only is liquid biopsy already making a difference in the lives of our patients, but there is so much more we can do to fully realize the impact of precision medicine through liquid biopsy for our patients,” said Erica Carpenter, MBA, PhD, an investigator in the study and Director of the Liquid Biopsy Laboratory at the University of Pennsylvania, Philadelphia.

She presented the study results just a day after they were published online (JAMA Oncol. 2018 Oct 11. Epub ahead of print).

Using Plasma Tests for Improved Detection

Tumor surveillance is traditionally conducted via tumor tests, imaging, and blood tests. Unlike the other methods, liquid biopsies can detect tumor materials that have been shed into the bloodstream. Other reasons liquid biopsies are preferable to other methods are because using tumor tissue samples can be suboptimal if a tumor is heterogenous, imaging may not be sensitive enough to detect tiny tumors, and patients experience less discomfort.

In the prospective cohort study by Dr Carpenter and colleagues, the objectives were to determine the proportion of patients who had targetable mutations detected in their plasma and tissue NGS; the link between the allele fractions (AFs) of mutations detected in tissue and plasma; and the relationship between response rate and plasma AF of the targeted mutations.

A total of 323 patients (mean age, 65 years; 60.1% women) with metastatic NSCLC underwent plasma NGS with a 73-gene commercial platform. These patients had plasma testing ordered as part of their routine clinical management and were enrolled at the Hospital of the University of Pennsylvania between April 1, 2016, and January 2, 2018.

Liquid Biopsies Improve Outcomes

In 113 (35.0%) of the 323 patients in the study, therapeutically targetable mutations were detected in EGFR, ALK, MET, BRCA1, ROS1, RET, ERBB2, or BRAF V600E. Liquid biopsies alone were conducted at the discretion of the treating physician or because of patient preference in 94 (29.1%) of cases. Among the patients who only underwent plasma testing, 31 (33.0%) had targetable mutations detected, which removed the need for an invasive biopsy.

For the 229 patients who underwent simultaneous plasma testing and tissue NGS (or who couldn’t have tissue NGS), targetable mutations were detected in tissue alone for 47 (20.5%) patients; adding plasma testing increased this number to 82 (35.8%).

A total of 42 patients received targeted therapy based on the results of their respective liquid biopsy; 36 (85.7%) of these patients achieved stable disease, a complete response, or a partial response. There was no correlation found between the plasma-based targeted mutation AF and the depth of response according to the Response Evaluation Criteria in Solid Tumors.

“This clinical study is, to our knowledge, one of the largest to measure the implications of plasma-based genotyping for the delivery of targeted therapy in NSCLC and clearly demonstrates that liquid biopsy can improve delivery of therapy and, consequently, outcomes,” said Dr Carpenter and her colleagues in the published results. —Hina Khaliq