KEY TAKEAWAYS
- The Phase III PROpel study was conducted with the aim of assessing the efficacy of Abiraterone (abi) + Olaparib (ola) Treatment as a first-line treatment for mCRPC and comparing it to Abiraterone + Placebo (pbo) treatment.
- Homologous recombination repair mutation (HRRm) status was evaluated using tumor tissue (FoundationOneCDx) and/or circulating tumor DNA.
- Abi+Ola treatment proved more beneficial across all subgroups with Amenia being the most reported Grade 3 AE.
- No fresh long-term safety concerns were found during this phase of the study.
PROpel is a phase 3 study of 1L therapy that is randomized, double-blind, and open to patients with mCRPC who are eligible for abiraterone. PROpel demonstrated a significant investigator-assessed radiographic progression-free survival (rPFS) advantage (hazard ratio [HR] 0.66, 95% confidence interval [CI] 0.54-0.81, P 0.001, data cut-off: 7/30/2021). At the time of the initial rPFS analysis (28.6% maturity, HR 0.86, 95% CI 0.66-1.12) and a later interim analysis (40.1% maturity, HR 0.83, 95% CI 0.66-1.03), a trend towards OS benefit with abi + ola was noted.
After 1:1 randomization to ola (300 mg twice daily [bid]) or pbo, and abi (1000 mg once daily) plus prednisone/prednisolone, patients were prospectively evaluated for homologous recombination repair mutation (HRRm) status using tumor tissue (FoundationOneCDx) and/or circulating tumor DNA (ctDNA; FoundationOneLiquid CDx) tests (5 mg bid). Treatment continued until the radiographic disease progressed, the toxicity became intolerable, or the patient withdrew permission. A crucial secondary outcome was OS (2-sided boundary for significance 0.0377). To classify patients into HRRm/BRCAm subgroups, tumor tissue, and ctDNA test findings were combined.
There was a fairly even distribution of patient (n = 796) characteristics, including prior docetaxel, site of metastasis, symptom score, and HRRm status. With abi + ola vs abi + pbo, there was a consistent tendency towards an OS benefit (maturity 47.9%, HR 0.81, 95% CI 0.67-1.00, P= 0.0544), with the median OS being 42.1 months (m) vs 34.7 m, respectively. For the HRRm, non-HRRm, BRCAm, and non-BRCAm subgroups, OS medians and HRs all preferred abi + ola over abi + pbo. Anemia (16.1%) was the most frequent Grade 3 adverse event in the abi + ola group.
At the predetermined final analysis in PROpel, abi + ola increased OS by more than 7 m in the ITT group compared to standard-of-care abiraterone (abi + pbo). The phase 3 trial in 1L mCRPC had the longest median OS recorded to date, at > 42 m. In line with the rPFS findings, a tendency towards OS benefit was seen in the HRRm, non-HRRm, BRCAm, and non-BRCAm subgroups, with the BRCAm subgroup showing the greatest benefit. There were no fresh long-term safety concerns found. The use of abi + ola in 1L mCRPC is supported by these findings.
Source: https://meetings.asco.org/abstracts-presentations/217650
clinical Trial: https://clinicaltrials.gov/ct2/show/NCT03732820
Clarke, N. W., Armstrong, A. J., Thiery-Vuillemin, A., Oya, M., Shore, N. D., Procopio, G., Guedes, J. D. C., Arslan, C., Mehra, N., Parnis, F., Emma Brown, E., Schlürmann, F., Joung, J. Y., Sugimoto, M., Sartor, O. A., Liu, Y. Z., Poehlein, C. H., Barker, L., del Rosario, P. M. & Saad F. (2023). J Clin Oncol 41, 2023 (suppl 6; abstr LBA16) DOI: 10.1200/JCO.2023.41.6_suppl.LBA16
