Molecular Response by Guardant360 Liquid Biopsy Translates to Clinical Outcomes in NSCLC

Screening patients for molecular response using the Guardant360 assay provides an early signal of antitumor activity for pembrolizumab-based treatment of non–small cell lung cancer.

Use of the Guardant360 liquid biopsy assay was able to identify patients with metastatic non–small cell lung cancer (NSCLC) who had a molecular response to pembrolizumab (Keytruda) based immunotherapy, which was likely to translate to a durable clinical benefit.

The results published in the JCO Precision Oncology revealed statistically significant improvements in end points of progression-free and overall survival in those with a molecular response versus nonresponders.1

“These are exciting results that further support the value of liquid biopsies as a noninvasive tool to measure early treatment responses by evaluating molecular response or changes in circulating tumor DNA,” Charu Aggarwal, MD, MPH, Leslye M. Heisler Associate Professor for Lung Cancer Excellence at Penn’s Perelman School of Medicine and Abramson Cancer Center, said in a press release.2 “We look forward to additional studies to help make this approach a reality in the clinical setting to personalize immunotherapy-based treatment decisions for patients with metastatic non–small cell lung cancer.”

The single-center, prospective, observational study included 51 patients who received pembrolizumab monotherapy or in combination with chemotherapy for metastatic non–small cell lung cancer. This group went on to receive sequential next-generation sequencing by blood sample at baseline and at 9 weeks to detect for changes in circulating tumor DNA (ctDNA) levels before and after therapy initiation.

A molecular response was defined as a 50% or greater decrease in the mean variant allele fraction by ctDNA. Tumor response by RECIST 1.1 was evaluated and a durable clinical response was defined as those having a complete or partial response or stable disease lasting over 6 months. Survival end points were also recorded.

Molecular response values were lower in patients with an objective radiologic response (log mean 1.25% vs 27.7%; P <.001). Patients considered to have a durable clinical benefit were also found to have lower molecular response values (3.5% vs 49.4%; P <.001). Longer median progression-free survival (14.1 versus 4.4 months; HR, 0.25; 95% CI, 0.13-0.50) and overall survival (22.1 vs 12.0 months; HR, 0.27; 95% CI, 0.12-0.64) were seen in molecular responders versus nonresponders.

“Unfortunately, only a subset of patients with metastatic non–small cell lung cancer will respond to pembrolizumab-based therapy, and their failure to achieve clinical benefit becomes evident after their disease has progressed,” Helmy Eltoukhy, Guardant Health CEO, said in a press release. “This study adds to the growing body of evidence showing that our Guardant360 test can effectively measure molecular response, giving clinicians an earlier indication whether to continue or stop treatment, explore other therapeutic regimens, or enroll the patient in a clinical trial.”

Guardant360 analyzes for the presence of genomic alterations in 83 different genes by ctDNA in blood samples of patients with cancer. The panel was approved in August 2020 for the detection of EGFR mutations in patients with metastatic NSCLC, representing the first liquid biopsy assay to receive FDA approval as a companion diagnostic test.3 Shortly after, it was approved as a tool for comprehensive genomic profiling in patients with solid tumor malignancies.4


1. Thompson JC, Carpenter EL, Silva BA, et al. Serial monitoring of circulating tumor dna by next-generation gene sequencing as a biomarker of response and survival in patients with advanced NSCLC receiving pembrolizumab-based therapy. JCO Prec Oncol. 2021;5:510-624. doi:10.1200/PO.20.00321

2. Study Shows Guardant360 Liquid Biopsy Predicts Response to Pembrolizumab-Based Immunotherapy in Patients with Metastatic Non-Small Cell Lung Cancer. News release. Guardant Health. March 29, 2021. Accessed April 4, 2021.

3. FDA Approves First Liquid Biopsy Next-Generation Sequencing Companion Diagnostic Test. FDA. August 7, 2020. Accessed April 4, 2021.

4. Guardant Health Guardant360® CDx First FDA-Approved Liquid Biopsy for Comprehensive Tumor Mutation Profiling Across All Solid Cancers. News release. Redwood City, California. Published August 7, 2020. Accessed April 4, 2021.