Multigene panel selection of patients suitable for targeted cancer therapies improves PFS

Compared to previous lines of therapy, targeted therapies significantly increased progression-free survival (PFS) in patients with cancer who were identified via multigene panel testing of their tumor samples. Researchers published their results in Cancer Discovery.

“The identification of genomic drivers of cancers and the development of targeted therapies have led to the hypothesis that testing for a large number of genes across all tumor types could improve outcomes for patients with advanced cancers,” said Fabrice André, MD, PhD, research director and head of INSERM Unit U981, and professor in the Department of Medical Oncology at Institut Gustave Roussy in Villejuif, France. “However, there is no evidence until now that such an approach actually results in improved outcomes.”

Indeed, previous trials had failed to find any significant benefits to molecularly driven therapeutic targeting. This may have been due to their use of old-generation targeted therapy that were not capable of superior target binding and/or bioactivity.

“We wanted to study whether identifying targeted therapies using a multigene panel would improve patient outcomes in a clinical trial,” said Jean Charles Soria, MD, PhD, professor of medicine at Institut Gustave Roussy. “In order to test this hypothesis, we compared the PFS under precision medicine with the PFS observed before the patient entered the trial. Each patient was therefore his/her own control,” he added.

Drs. Andre and Soria began the Molecular Screening for Cancer Treatment Optimization (MOSCATO 01) study, and enrolled 1,035 patients with advanced, unresectable, or metastatic cancer between 2011 and 2016 that had progressed after at least one line of previous therapy.

Tumor biopsies were gathered from 948 subjects, most commonly cancers of the digestive tract, lung, urologic, breast, and head and neck, and researchers performed DNA sequencing on 843 of these samples. The most frequent alterations were seen in genes PIK3CA, ERBB2, PtEN, FGFR1, EGFR, and NOTCH.

Drs. Andre and Soria and colleagues then compared PFS from patients who underwent molecularly driven treatment with PFS from previous therapies, to assure that it would be > 1.3 (PFS2/FPS1 > 1.3) in over 15% of subjects.

They found a PFS2/PFS1 > 1.3 in a full 33% of patients. After targeted therapy, two patients had complete responses, while 20 had partial, for an overall response rate of 11%. Further, 100 had stable disease, and 33 progressive disease. Median overall survival was 11.9 months.

“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 Dr. Soria.

This study was funded by Fondation Gustave Roussy (Revolution Cancer initiative), INCa-DGOS-INSERM 6043 (SIRIC SOCRATE), ANR-10-IBHU-0001(MMO), and unrestricted grants from Genentech and Sanofi.