KEY TAKEAWAYS
- A phase 3 PROpel study demonstrated a significant investigator-assessed rPFS benefit for patients with mCRPC treated with abi + ola compared to abi + pbo in the 1L setting.
- A trend toward an OS benefit with abi + ola was observed at the time of the primary rPFS analysis and subsequent interim analysis, and the pre-planned final analysis (data cut-off: 10/12/2022) reported OS and safety results.
- The ITT population showed a consistent trend toward OS benefit with abi + ola, with a median OS of 42.1 months compared to 34.7 months for abi + pbo, and a hazard ratio of 0.81 and a 95% confidence interval of 0.67-1.00 (P=0.0544).
- The most common Grade ≥3 adverse event in the abi + ola arm was anemia (16.1%), and no new long-term safety issues were identified. In addition, abi + ola demonstrated benefit across HRRm, non-HRRm, BRCAm, and non-BRCAm subgroups, with the greatest benefit observed in the BRCAm subgroup.
Patients with mCRPC treated with abi + ola vs abi + pbo in the 1L setting had a statistically significant improvement in radiographic progression-free survival (rPFS) (hazard ratio [HR] 0.66, 95% confidence interval [CI] 0.54-0.81, P 0.001, data cut-off: 7/30/2021) according to an investigator assessment. The results of a centralized, independently conducted sensitivity study were reliable. In the primary rPFS analysis (28.6% maturity, HR 0.86, 95% CI 0.66-1.12) and the second interim analysis (40.1% maturity, HR 0.83, 95% CI 0.66-1.03), there was a suggestion of an OS benefit with abi + ola.
Patients with metastatic castration-resistant prostate cancer who are candidates for abiraterone are being recruited for the PROpel trial, a randomized, double-blind, phase 3 study of 1L treatment. Patients were randomized 1:1 to ola (300 mg bid) or pbo, and abi (1000 mg once daily) plus prednisone/prednisolone, and then 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). Radiographic disease progression, intolerable toxicity, or withdrawal of consent prompted discontinuation of treatment.
One of the most important tertiary outcomes was the operating system (2-sided boundary for significance 0.0377). To classify patients into HRRm/BRCAm subgroups, we used test results from tumor tissue and ctDNA. The features of the patients (n = 796) were very even across all categories (previous docetaxel, site of metastases, symptom score, and HRRm status). Median OS was 42.1 months (m) with abi + ola versus 34.7 months (m) with abi + pbo in the intention-to-treat (ITT) population (maturity 47.9%, HR 0.81, 95% CI 0.67-1.00, P= 0.0544). Median OS and hazard ratios (HRs) all supported abi + ola vs abi + pbo in the HRRm, non-HRRm, BRCAm, and non-BRCAm subgroups. Anemia was the most common adverse event of Grade 3 in the abi + ola group (16.1%).
In the intent-to-treat (ITT) population of PROpel, abi + ola improved OS by > 7 months compared to the gold standard of care (abi + pbo). Median overall survival was the longest ever reported for first-line metastatic castration-resistant prostate cancer in a randomized, controlled phase 3 trial. There was a trend towards OS benefit in the BRCAm subgroup, although this benefit was shown in the HRRm, non-HRRm, BRCAm, and non-BRCAm categories, all consistent with the rPFS data. It was determined that there would be no new dangers over the long run.
Source: https://meetings.asco.org/abstracts-presentations/217650
Clinical trial: https://clinicaltrials.gov/ct2/show/NCT03732820/
Noel W. Clarke, Andrew J. Armstrong, Antoine Thiery-Vuillemin, Mototsugu Oya, Neal D. Shore, Giuseppe Procopio, João Daniel Cardoso Guedes, Cagatay Arslan, Niven Mehra, Francis Parnis, Emma Brown, Friederike Schlürmann, Jae Young Joung, Mikio Sugimoto, A. Oliver Sartor, Yu-Zhen Liu, Christian Heinrich Poehlein, Laura Barker, Paula Michelle del Rosario, Fred Saad – J Clin Oncol 41, 2023 (suppl 6; abstr LBA16)
