Olaparib for Metastatic Castration-Resistant Prostate Cancer With BRCA1 and/or BRCA2 Alterations

[Balsam01]

I know these results have been known for a while but me being germline and somatic BRCA 2, I thought it would be important to post this for those warriors with this condition.

TAKE-HOME MESSAGE

The phase III PROfound trial showed that patients with metastatic castration-resistant prostate cancer who have BRCA and/or ATM mutations had improved survival outcomes with olaparib monotherapy compared with abiraterone or enzalutamide therapy. In this study, the results of the post hoc analysis of patients with BRCA mutations were reported. A radiographic progression–free survival benefit was observed among all zygosity subgroups (biallelic, heterozygous, and unknown). However, patients with BRCA2 homozygous deletions had the most prolonged responses. Between patients with somatic BRCA alterations and those with germline BRCA alterations, the risk of disease progression was similar.

Olaparib monotherapy improved outcomes in patients with metastatic castration-resistant prostate cancer with BRCA alterations, regardless of their subgroup (zygosity, germline, or somatic).

– Yael Kusne, MD, PhD

PURPOSE

Phase III PROfound trial (ClinicalTrials.gov identifier: NCT02987543) met its primary and key secondary objectives, demonstrating significantly longer radiographic progression-free survival (rPFS) and overall survival (OS) with olaparib monotherapy versus abiraterone or enzalutamide (control) in patients with metastatic castration-resistant prostate cancer (mCRPC) with alterations in BRCA1, BRCA2 (BRCA), and/or ATM (cohort A) whose disease had progressed on prior next-generation hormonal agent (NHA). We report exploratory post hoc analysis of the subgroup of patients with mCRPC with BRCA alterations in PROfound.

METHODS

All patients had an alteration in a homologous recombination repair gene by tumor tissue testing, of which 160 had underlying BRCA alterations. rPFS and OS were estimated using the Kaplan-Meier method. Confirmed objective response rate and safety were also assessed.

RESULTS

Olaparib was associated with longer rPFS (hazard ratio [HR], 0.22 [95% CI, 0.15 to 0.32]) and OS (HR, 0.63 [95% CI, 0.42 to 0.95]) than control. There was an rPFS benefit with olaparib in all zygosity subgroups (biallelic [n = 88]; HR, 0.08 [95% CI, 0.04 to 0.16], heterozygous [n = 15] and unknown [n = 57]; HR, 0.30 [95% CI, 0.16 to 0.60]). Patients with BRCA2 homozygous deletions experienced prolonged responses to olaparib (n = 16; median rPFS, 16.6 months [95% CI, 9.3 to not reached]). Some evaluations are limited by small patient numbers. Germline DNA analysis was performed for 112 (70%) patients; risk of disease progression was similar for patients with germline (n = 61; HR, 0.08 [95% CI, 0.03 to 0.18]) and somatic (n = 51; HR, 0.16 [95% CI, 0.07 to 0.37]) BRCA alterations.

CONCLUSION

In all subgroups assessed, olaparib improved outcomes versus abiraterone or enzalutamide for patients with mCRPC with BRCA alterations whose disease had progressed on previous NHA.

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Article Citation

Journal of Clinical Oncology

Olaparib for the Treatment of Patients With Metastatic Castration-Resistant Prostate Cancer and Alterations in BRCA1 and/or BRCA2 in the PROfound Trial

J. Clin. Oncol 2023 Nov 14;[EPub Ahead of Print], J Mateo, JS de Bono, K Fizazi, F Saad, N Shore, S Sandhu, KN Chi, N Agarwal, D Olmos, A Thiery-Vuillemin, M Özgüroğlu, N Mehra, N Matsubara, J Young Joung, C Padua, E Korbenfeld, J Kang, H Marshall, Z Lai, A Barnicle, C Poehlein, N Lukashchuk, M Hussain

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

[mrscruffy]

Started Lynparza 8 weeks ago. Blood test next Monday