Henrik Grönberg, MD

Formal discussant of the PROfound trial, Henrik Grönberg, MD, of the Karolinska Institute, Stockholm, agreed that this was a practice-changing trial for select patients.

“The patient population is representative, but the problem is the control group, which included patients who experienced disease progression on one or both androgen receptor inhibitors and then put on another by physician’s choice. You have to conclude that the treatments for the control group were ineffective, and that has a bearing on analysis. Also, it is difficult to analyze overall survival after crossover, and we need a better understanding of the findings,” Dr. Grönberg commented.

“It’s clear that the effect of olaparib is superior in BRCA1 and BRCA2 cohorts and not as robust in the ATM cohort. The effect of olaparib in cohort B—with 12 other mutations—is very small if any,” he continued. “I would like to see more detailed analyses of quality of life.”

Clinical Implications

“Biomarker-guided treatment is the future,” Dr. Grönberg noted. “Use biomarkers prospectively and use the best method to evaluate biomarkers. Never forget that we treat real patients, not study participants. We should be restrictive in allowing crossover in clinical trials, particularly in late-stage disease,” he added.

“Based on the PROfound results, I would most likely treat my patients with BRCA1- and BRCA2-positive metastatic castration-resistant prostate cancer [with olaparib] who have received standard treatments and experienced disease progression. However, I would not use this drug in patients with other genetic alterations,” Dr. Grönberg stated. 

Publisher's Note: This article was originally published in the October 25, 2020 issue of The ASCO Post.

DISCLOSURE: Dr. Grönberg has received honoraria from Astellas Pharma, Bristol Myers Squibb, and Janssen Oncology and holds five pending patents related to the diagnosis of prostate cancer.