Genomic Analyses Guide Targeted Therapies for Metastatic Cancers
High-throughput genomic analyses may improve outcomes in patients with types of metastatic cancer, according to results of a recent trial published in Cancer Discovery (published online April 1, 2017; doi:10.1158/2159-8290.CD-16-1396).
In recent years, the identification of genomic drivers of cancer and the development of targeted therapies have led oncologists to believe that testing for a large number of genes across all tumor types may improve outcomes for patients with advanced diseases.
Fabrice André, MD, PhD, Institut Gustave Roussy (France), and colleagues organized the Molecular Screening for Cancer Treatment Optimization trial to evaluate the clinical benefit of using high-throughput genomic analyses for improving outcomes in patients with advanced cancers. Researchers enrolled 1035 adult patients with advanced, unresectable, or metastatic cancer who had progressed after at least 1 prior therapy between 2011 and 2016. Tumor biopsies were obtained from 948 patients and DNA sequencing were performed on 843 patients. The primary objective was to evaluate clinical benefit, measured by the percentage of patients demonstrating progression-free survival (PFS) on matched therapy 1.3-fold longer than the PFS on prior therapy.
The most frequent cancer types among the patient population were of the digestive tract (21%), lung (18%), urological (16%), breast (14%), and head and neck (12%). An actionable target was identified in 411 patients, 199 of whom received a targeted therapy that matched the genomic alteration identified. The most frequent alterations observed were in the genes PIK3CA, ERBB2, PTEN, FGFR1, EGFR, and NOTCH.
Results of the study showed the ratio of PFS on matched therapy to PFS on prior therapy was greater than 1.3 in 33% of the patients. Objective responses were demonstrated in 11% of patients (2 complete responses, 20 partial responses) and median overall survival was 11.9 months with matched therapy. A total of 100 patients had stable disease and 33 patients progressed while on matched therapy.
Researchers acknowledged that this was not a randomized trial, thus limiting the value of the outcomes for patients who received targeted therapies relative to the outcomes of those who did not or those with similar diseases but without the matched genomic alterations.
“Our study shows that high-throughput genomics is likely to improve outcomes for some patients with hard-to-treat cancers, nevertheless, this needs to be validated in a larger, randomized trial,” said Jean Charles Soria, MD, PhD, author of the study, in a press release (April 1, 2017). – Zachary Bessette