Study reveals real-world data of PFS, OS with olaparib for mCRPC

A retrospective observational study sheds light on real-world time on treatment, progression-free survival, and overall survival in patients with metastatic castration-resistant prostate cancer (mCRPC) with homologous recombination repair gene mutations (HRRm) receiving monotherapy treatment with the PARP inhibitor olaparib (Lynparza).¹

Daniel J. George, MD

The study findings were presented at the Society of Urologic Oncology 25th Annual Meeting by a team of investigators led by Daniel J. George, MD, director of GU Oncology at Duke Cancer Center in Durham, North Carolina.

In describing the background for the study, the authors wrote in their poster, “There is a lack of studies assessing real-world biomarker testing patterns and outcomes in patients with mCRPC who receive olaparib monotherapy.”

For the study, the investigators utilized the ConcertAI Oncology Dataset, which includes de-identified electronic medical record data derived from geographically diverse and primarily community oncology practices from rural and urban areas.

Patients with confirmed mCRPC diagnosed between 2012 and 2023 and who were 21 years of age or older, were treated with olaparib monotherapy after exposure to abiraterone acetate (Zytiga) or enzalutamide (Xtandi), and who had positive HRRm status were eligible for inclusion in the study. The genes of interest for the analysis included ATM, BARD1, BRCA1, BRCA2, BRIP1, CDK12, CHEK1, CHEK2, FANCL, PALB2, RAD51B, RAD51C, RAD51D, and RAD54L. Patients were excluded from the study if they had received a diagnosis of primary cancer(s) other than prostate cancer or non-melanoma skin cancer or who were enrolled in an interventional clinical trial on or after diagnosis of mCRPC.

Patients were stratified according to line of earliest olaparib monotherapy and treatment before olaparib monotherapy (next-generation hormonal agent [NHA] without chemotherapy or NHA with prior chemotherapy).

The investigators identified 144 patients who received mCRPC treatment with olaparib monotherapy. Fifty-nine (41.0%) patients started olaparib monotherapy in the first 3 lines (≤3L), and 85 patients (59.0%) started olaparib monotherapy in the fourth line and beyond (4L+).

Sixty-five (45.1%) patients received an NHA with chemotherapy before olaparib monotherapy, and 79 (54.9%) received an NHA without chemotherapy before olaparib monotherapy.

The median time from index date (defined as the start date of earliest olaparib monotherapy treatment) to end of patient record or data cut-off was 8.2 months in the ≤3L group and 7.7 months in the 4L+ group, and 9.4 months in patients who received a prior NHA without chemotherapy and 7.1 months in patients who received a prior NHA with prior chemotherapy.

Regarding biomarker testing, overall median time from first documented biomarker test date to index date was 5.5 months. Median time from first documented biomarker test date to index date was 3.5 months in the ≤3L group and 7.8 months in the 4L+ group and 3.7 months in patients who received a prior NHA without chemotherapy and 7.8 months in patients who received a prior NHA with prior chemotherapy.

The median real-world time on treatment for earliest olaparib monotherapy was 4.6 months overall (95% CI: 3.5-5.5) and 5.3 months (95% CI: 4.0-8.2) in the ≤3L group, 3.8 months (95% CI: 2.1-5.5) in the 4L+ group, 4.8 months (95% CI: 3.5-8.1) in patients who received a prior NHA without chemotherapy, and 4.0 months (95% CI: 2.1-5.5) in patients who received a prior NHA with prior chemotherapy.

Median real-world progression-free survival for earliest olaparib monotherapy was 4.5 months overall (95% CI: 3.6-5.6) and 5.3 months (95% CI: 3.6-6.8) in the ≤3L group, 3.9 months (95% CI: 3.2-5.5) in the 4L+ group, 5.1months (95% CI: 3.5-6.8) in patients who received a prior NHA without chemotherapy, and 4.2 months (95% CI: 3.2-5.6) in patients who received a prior NHA with prior chemotherapy.

Median real-world overall survival for earliest olaparib monotherapy was 16.5 months overall (95% CI: 12.4-21.2) and 16.5 months (95% CI: 11.7-24.1) in the ≤3L group, 15.0 months (95% CI: 11.0-21.0) in the 4L+ group, 21.1months (95% CI: 12.4-24.1) in patients who received a prior NHA without chemotherapy, and 14.7 months (95% CI: 10.6-20.3) in patients who received a prior NHA with prior chemotherapy.

“The results from this real-world analysis suggest that patients may benefit from improved outcomes with earlier biomarker testing and would allow for earlier treatment with targeted therapy in the disease course when appropriate. Additionally, retesting for previously unrecognized or acquired mutations should also be considered,” the authors wrote in their conclusion.

REFERENCE

1. George DJ, Kariburyo-Yay F, Aggarwal H, et al. Real-world treatment and clinical outcomes in patients with metastatic castration-resistant prostate cancer treated with olaparib in the United States. Presented at: Society of Urologic Oncology 25th Annual Meeting. December 4-6, 2024. Dallas, Texas. Abstract 3. Accessed December 4, 2024. https://suo-abstracts.secure-platform.com/a/gallery/rounds/21/details/3611