PHILADELPHIA — The progression-free survival rate (PFS) in cancer patients treated with targeted therapies (identified using a multigene panel test on their tumor samples) was significantly higher than the PFS in these patients when they were treated with previous line of therapy, according to clinical trial data published in Cancer Discovery, a journal of the American Association for Cancer Research.
“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.”
“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,” Soria said.
Soria, André, and colleagues initiated the Molecular Screening for Cancer Treatment Optimization (MOSCATO 01) trial to test their hypothesis. Between 2011 and 2016, they enrolled 1,035 adult patients with advanced, unresectable, or metastatic cancer that had progressed after at least one line of prior therapy.
The investigators were able to obtain a tumor biopsy from 948 patients, and performed DNA sequencing on 843; most frequent cancers types were of the digestive tract, lung, urological, breast, and head and neck. An actionable target was identified in 411 patients, and of these patients, 199 received a targeted therapy that matched the genomic alteration identified.
In these patients’ tumors, the most frequent alterations were observed in the genes PIK3CA, ERBB2, PTEN, FGFR1, EGFR, and NOTCH.
The investigators tested the hypothesis that the ratio of the PFS from the molecularly driven therapy to the PFS from prior therapy would be greater than 1.3 (PFS2/PFS1 >1.3) in more than 15 percent of the patients.
Study results showed a PFS2/PFS1 >1.3 in 33 percent of the patients. Following targeted therapy, of the evaluable patients, two had complete responses and 20 had partial responses, for an overall response rate of 11 percent; 100 had stable disease and 33 had 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,” Soria said. A couple of earlier trials that evaluated the efficacy of molecularly driven therapeutic targeting did not find any significant benefit. Soria explained that one of the reasons could be that those trials used old-generation targeted therapies that may not have had superior target binding and/or bioactivity.
Limitations of the study include that this was not a randomized trial; therefore, the outcomes from patients who received targeted therapies could not be compared with the outcomes from those who received nontargeted therapies or with the outcomes from patients with similar disease but without the matched genomic alterations, André said.
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. André and Soria declare no conflicts of interest.