Celestia S. Higano, MD
Formal discussant Celestia S. Higano, MD, Adjunct Professor in the Department of Urologic Sciences at the University of British Columbia, Vancouver, had the task of reviewing the results of both the MAGNITUDE and PROpel trials, which were presented at the same session. Of the two trials, PROpel has a more familiar design in that it is a straightforward phase III design enrolling all comers. In contrast, MAGNITUDE allocates patients to homologous recombination repair (HRR)-positive and HRR-negative cohorts, enriches for patients with BRCA1/2–mutated disease, and does a futility analysis on the HRR cohort.
Looking at both arms of PROpel, the HRR status was balanced between the two arms. “The investigators did not report BRCA1/2 mutation–positive status, but my guesstimate is that it mirrors the expected percentage (3%–5%), whereas the HRR-positive MAGNITUDE population was enriched for BCRA1/2–mutated patients, who made up 53% of that subgroup. This is important because patients with BRCA1/2 mutations have worse outcomes and more aggressive disease,” Dr. Higano explained.
“In PROpel, the median radiographic progression-free survival in the combination arm of 27.6 months is one of the longest ever reported. The radiographic progression-free survival in the combination arm of MAGNITUDE was 16.5 months, but this should not be interpreted to mean that olaparib is better than niraparib. The findings merely reflect the very different study populations,” she cautioned the audience.
“The take-home message from PROpel is that we should wait for overall survival results and a better understanding of which patients benefit the most before using this combination in the clinic for first-line therapy [for metastatic CPRC],” she said.
DISCLOSURE: Dr. Higano owns stock in CTI BioPharma Corp; has served as a consultant or advisor to Astellas Pharma, AstraZeneca, Genentech, Menarini, Merck Sharp & Dohme, Myovant Sciences, Tolmar, and Vaccitech; and has received institutional research funding from Astellas Pharma, AstraZeneca, Bayer, Clovis Oncology, eFFECTOR Therapeutics, Ferring, Medivation, Pfizer, and Roche.
