ALLOCATE Trial: Is Targeted Molecular Profiling Useful in Treating Ovarian Cancer?
Posted: Wednesday, August 14, 2019
According to the results from the pilot ALLOCATE study, presented in JCO Precision Oncology, real-time targeted molecular profiling may be able to identify known genomic and methylation alterations of various ovarian cancer subtypes. Timely reporting of such alterations, as observed by Olga Kondrashova, PhD, of the University of Melbourne, Australia, and colleagues, may prove to be useful in routine clinical practices.
“Better patient selection and access to a wider range of targeted therapies or clinical trials will further enhance the clinical utility of molecular profiling,” the authors concluded.
The investigators focused on 99 patients with cases suitable for prospective analysis from two tertiary hospitals. Dr. Kondrashova and colleagues performed targeted molecular and methylation profiling of fresh biopsies and archived tumor samples by utilizing screenings for mutations or copy-number variations in 44 genes and for promoter methylation of BRCA1 and RAD51C genes.
The investigators identified somatic genomic or methylation events in 85% of all patients, with potential actionable events with defined targeted therapies—including four resistance events—in 60% of all patients. Because of these findings, six patients underwent molecularly guided therapy. In three patients, molecular profiling detected unsuspected germline cancer-associated BRCA1/2 mutations, and they were referred to genetic counseling. And two patients had intermediate differentiated grade 2 serous ovarian carcinoma reclassified as low grade. For two patients, secondary reversion mutations in BRCA1/2 genes were found in fresh biopsy samples that were consistent with clinical platinum/polymerase inhibitor resistance.
The authors observed that timely reporting of results from molecular testing at the time of disease recurrence, as well as early referral for patients with platinum-resistant cancers, are potential factors in improving the clinical benefits of molecular profiling.
Disclosure: The study authors’ disclosure information may be found at ascopubs.org.