Untangling the PROfound Trial for Advanced Prostate Cancer: Is There Really a Role for Olaparib?

Daniel H Kwon; Christopher M Booth; Vinay Prasad

doi:10.1016/j.eururo.2021.02.041

Untangling the PROfound Trial for Advanced Prostate Cancer: Is There Really a Role for Olaparib?

Eur Urol. 2021 Jun;79(6):710-712. doi: 10.1016/j.eururo.2021.02.041. Epub 2021 Mar 12.

Authors

Daniel H Kwon¹, Christopher M Booth², Vinay Prasad³

Affiliations

¹ Division of Hematology/Oncology, Department of Medicine, University of California, San Francisco, San Francisco, CA, USA.
² Department of Oncology, Queen's University, Kingston, ON, Canada.
³ Division of Hematology/Oncology, Department of Medicine, University of California, San Francisco, San Francisco, CA, USA; Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, CA, USA. Electronic address: [email protected].

PMID: 33722420
DOI: 10.1016/j.eururo.2021.02.041

Abstract

The phase 3 PROfound trial led to the recent approval of the PARP inhibitor olaparib for men with metastatic castration-resistant prostate cancer and mutations in homologous recombination repair genes. We raise methodological concerns about the trial, including: a suboptimal control arm, problematic use of crossover, use of radiographic progression-free survival as the primary endpoint, and ambiguous benefit for patients with mutations in homologous recombination repair genes other than BRCA1, BRCA2, and ATM.

Publication types

Editorial
Research Support, Non-U.S. Gov't

MeSH terms

Humans
Male
Phthalazines / adverse effects
Phthalazines / therapeutic use*
Piperazines / therapeutic use*
Poly(ADP-ribose) Polymerase Inhibitors / adverse effects
Prostatic Neoplasms, Castration-Resistant* / drug therapy
Prostatic Neoplasms, Castration-Resistant* / genetics

Substances

Phthalazines
Piperazines
Poly(ADP-ribose) Polymerase Inhibitors
olaparib