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Expert Point of View: Celestia S. Higano, MD


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MAGNITUDE is challenging from a statistical point of view,” said formal discussant Celestia S. Higano, MD, currently Adjunct Professor, Department of Urologic Sciences at the University of British Columbia, Vancouver, Canada, and formerly of Fred Hutchinson Cancer Research Center in Seattle.

“MAGNITUDE had patients preselected according to biomarker status, and there are advantages and disadvantages to this, including the potential for overtreating biomarker-negative patients,” she told the audience. “The statistics of this trial are quite complex, and there really are two separate trials—the biomarker-negative and biomarker-positive cohorts. Within the biomarker-positive cohort, there are two separate analyses for BRCA-positive and all HRR [homologous recombination repair]-positive patients.”

Celestia S. Higano, MD

Celestia S. Higano, MD

Drilling down to the details, Dr. Higano estimated that there were 10 times more patients with BRCA2 mutation in MAGNITUDE than in PROpel, a separate phase III trial also presented at the 2022 ASCO Genitourinary Cancers Symposium. This other trial found that the combination of the PARP inhibitor olaparib plus abiraterone was superior to abiraterone alone in men with metastatic castration-resistant prostate cancer regardless of HRR status. (The PROpel trial will be discussed in a future issue of The ASCO Post.)

“These patients [ie, with BRCA1/2] are known to have a worse outcome and more aggressive disease,” Dr. Higano stated. “Having all HRR-positive patients in the trial waters down the differences between the those with BRCA1/2 and those with HRR.”

Dr. Higano suggested a cautious approach, based on the MAGNITURE results to date. “The combination of niraparib plus abiraterone and prednisone should not be used in all HRR-positive patients until we have overall survival data and more detailed biomarker analysis. For BRCA1/2-positive patients, I would hedge my bets, and the combination might be a reasonable option given the poor outcomes of these patients. We still need overall survival data for those patients as well,” Dr. Higano stated.

DISCLOSURE: Dr. Higano has received honoraria from Astellas Pharma; has served as a consultant or advisor to AstraZeneca, Bayer, Blue Earth Diagnostics, Carrick Therapeutics, Clovis Oncology, Ferring, Hinova, Janssen, Merck Sharp & Dohme, Novartis, and Pfizer; has received institutional research funding from Aragon Pharmaceuticals, Astellas Pharma, AstraZeneca, Bayer, Clovis Oncology, ­Effector Therapeutics, Emergent BioSolutions, Ferring Pharmaceuticals, Medivation, Pfizer, and Roche; and has been reimbursed for travel, accommodations, or other expenses by Bayer, Blue Earth Diagnostics, Carrick Therapeutics, Clovis ­Oncology, Ferring, Hinova Pharmaceuticals, Janssen Oncology, Merck Sharp & Dohme, Novartis, and Pfizer.

 


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