(UroToday.com) At the second prostate cancer session at the 2020 Annual Meeting of the Society of Urologic Oncology (SUO), Dr. Maha Hussain presented the results of the PROfound study, Study of Olaparib (Lynparza™) Versus Enzalutamide or Abiraterone Acetate in Men With Metastatic Castration-Resistant Prostate Cancer (PROfound Study), which demonstrated the superiority of olaparib, a poly (adenosine diphosphate-ribose) polymerase inhibitor, for treatment of metastatic castrate-resistant prostate cancer (mCRPC).
After a brief discussion of the TOPARP trial and some of the rationale which lead to the genesis of the PROfound study, Dr. Hussain launched into a discussion of the trial itself. In this trial, published in the New England Journal of Medicine in May 20201 with an update in the same journal in September2, patients with the following characteristics were enrolled:
- Metastatic hormone-resistant prostate cancer
- Progression on a new hormonal agent (e.g. abiraterone or enzalutamide)
- A mutation in at least one allele one of 15 prespecified genes (BRCA1, BRCA2, ATM, BRIP1, BARD1, CDK12, CHEK1, CHEK2, FANCL, PALB2, PPP2R2A, RAD51B, RAD51C, RAD51D, and RAD54L) as assessed on a trial assay based on the FoundationOne CDx next-generation sequencing test
There were no restrictions based on ECOG status, volume or location of metastases, or prior taxane therapy.
Patients with mutations in BRCA1, BRCA2, ATM were called and “cohort A” and were the primary population for the analysis.
These patients were randomized to olaparib 300mg twice-daily vs the physician's choice of abiraterone or enzalutamide. The primary endpoint was imaging-based progression-free survival in cohort A based on blinded central review.
Results in the full population were similar, as were results from numerous prespecified subgroup analyses, including patients with and without prior taxane use, bone only and visceral metastases, and baseline ECOG score of 0 and 1.
This data lead to the United States Federal Drug Administration (FDA) to approve olaparib for patients with mCRCP with deleterious or suspected deleterious germline or somatic homologous recombination repair mutations who have progressed on enzalutamide or abiraterone. This recommendation was similarly adopted in the National Comprehensive Cancer Network® (NCCN®) guidelines.
Presented by: Maha H.A. Hussain, MD, FACP, FASCO, Genevieve Teuton Professor of Medicine, Division of Hematology-Oncology, Department of Medicine, Northwestern University Feinberg School of Medicine
Written by: Marshall Strother, MD, Society for Urologic Oncology Fellow, Division of Urologic Oncology, Fox Chase Cancer Center, Philadelphia PA, @mcstroth during the 2020 Society of Urologic Oncology Annual Meeting – December 2-5, 2020 – Washington, DC
References:
2. Hussain M, Mateo J, Fizazi K, et al. Survival with olaparib in metastatic castration-resistant prostate cancer. N Engl J Med. Published online September 20, 2020:NEJMoa2022485.
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