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    PROpel: Phase III trial of olaparib (ola) and abiraterone (abi) versus placebo (pbo) and abi as first-line (1L) therapy for patients (pts) with metastatic castration-resistant prostate cancer (mCRPC)

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    Authors
    Saad, F.
    Armstrong, A. J.
    Thiery-Vuillemin, A.
    Oya, M.
    Loredo, E.
    Procopio, G.
    de Menezes, J. J.
    Girotto, G. C.
    Arslan, C.
    Parnis, N. M. F.
    Parnis, F.
    Brown, E.
    Schlurmann, F.
    Joung, J. Y.
    Sugimoto, M.
    Poehlein, C. H.
    Harrington, E.
    Desai, C.
    Kang, J. Y.
    Clarke, Noel W
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    Affiliation
    Centre Hospitalier de l’Université de Montréal/CRCHUM, Montreal, QC, Canada
    Issue Date
    2022
    
    Metadata
    Show full item record
    Abstract
    Background: Preclinical studies have shown combined anti-tumor effect through interactions between poly(adenosine diphosphate–ribose) polymerase and androgen receptor signaling pathways. A Phase II trial (NCT01972217) in pts with mCRPC unselected by homologous recombination repair (HRR) status who previously received docetaxel demonstrated improved radiographic progression-free survival (rPFS) for pts treated with ola + abi vs pbo + abi (Clarke N, 2018). The Phase III PROpel study (NCT03732820) evaluates the efficacy and safety of ola + abi in the 1L mCRPC setting. Methods: PROpel is a randomized, double-blind, placebo-controlled Phase III trial in pts with mCRPC undergoing 1L treatment after failure of primary androgen deprivation therapy, enrolled independent of HRR status. Pts were randomized 1:1 to receive ola (300 mg twice daily [bid]) or pbo, and abi (1000 mg once daily) + prednisone or prednisolone (5 mg bid). The primary endpoint was investigator-assessed rPFS with multiple secondary endpoints, including overall survival (OS). Results:796 pts were randomized to ola + abi (n=399) or pbo + abi (n=397).In this planned interim analysis, 1L treatment with ola + abi significantly prolonged rPFS vs pbo + abi in pts with mCRPC irrespective of HRR status (24.8 vs 16.6 months; hazard ratio [HR] 0.66, 95% confidence interval [CI] 0.54–0.81; P <0.0001). Predefined subgroup analyses showed rPFS improvement across all subgroups, including pts with (HR 0.54, 95% CI 0.36–0.79) and without (HR 0.76, 95% CI 0.59–0.97) HRR mutations detected by circulating tumor DNA testing. A sensitivity analysis of rPFS by blinded independent central review was consistent with the primary analysis (HR 0.61, 95% CI 0.49–0.74; P=0.004). OS is currently immature with 228 deaths (28.6%). A trend in OS favoring ola + abi was observed (HR 0.86, 95% CI 0.66–1.12). Secondary endpoints of time to first subsequent treatment (HR 0.74, 95% CI 0.61–0.90) and time to second progression-free survival or death (HR 0.69, 95% CI 0.51–0.94) were supportive of long-term benefits. The most common grade ≥3 adverse event (AE) reported was anemia (15.1 vs 3.3%) for ola + abi vs pbo + abi; 13.8 vs 7.8% pts, respectively, discontinued ola/pbo because of an AE. The rate of AEs leading to abi discontinuation were similar in both arms (8.5 vs 8.8%). Conclusions: At interim analysis, PROpel met its primary objective, demonstrating significant improvement in rPFS for ola + abi vs pbo + abi in pts with newly detected mCRPC who had not received prior 1L therapy, irrespective of HRR status. The safety and tolerability profile of ola + abi was consistent with the known safety profiles of the individual drugs. These results demonstrate the benefit of ola + abi without the need for HRR stratification in 1L treatment of mCRPC. Pt follow-up is ongoing for the planned OS analysis.
    Citation
    Saad F, Armstrong AJ, Thiery-Vuillemin A, Oya M, Loredo E, Procopio G, et al. PROpel: Phase III trial of olaparib (ola) and abiraterone (abi) versus placebo (pbo) and abi as first-line (1L) therapy for patients (pts) with metastatic castration-resistant prostate cancer (mCRPC).. Vol. 40, Journal of Clinical Oncology. American Society of Clinical Oncology (ASCO); 2022. p. 11–11.
    Journal
    Journal of Clinical Oncology
    URI
    http://hdl.handle.net/10541/625248
    DOI
    10.1200/JCO.2022.40.6_suppl.011
    Additional Links
    https://dx.doi.org/10.1200/JCO.2022.40.6_suppl.011
    Type
    Meetings and Proceedings
    Language
    en
    ae974a485f413a2113503eed53cd6c53
    10.1200/JCO.2022.40.6_suppl.011
    Scopus Count
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