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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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Saad, F; Armstrong, AJ; Thiery-Vuillemin, A; Oya, M; Loredo, E; Procopio, G; Janoski de Menezes, J; Girotto, GC; Arslan, C; Mehra, N; Parnis, F ...
Published in: Journal of Clinical Oncology
February 20, 2022

11 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. Clinical trial information: NCT03732820.

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Published In

Journal of Clinical Oncology

DOI

EISSN

1527-7755

ISSN

0732-183X

Publication Date

February 20, 2022

Volume

40

Issue

6_suppl

Start / End Page

11 / 11

Publisher

American Society of Clinical Oncology (ASCO)

Related Subject Headings

  • Oncology & Carcinogenesis
  • 3211 Oncology and carcinogenesis
  • 1112 Oncology and Carcinogenesis
  • 1103 Clinical Sciences
 

Citation

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Saad, F., Armstrong, A. J., Thiery-Vuillemin, A., Oya, M., Loredo, E., Procopio, G., … Clarke, N. (2022). 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). In Journal of Clinical Oncology (Vol. 40, pp. 11–11). American Society of Clinical Oncology (ASCO). https://doi.org/10.1200/jco.2022.40.6_suppl.011
Saad, Fred, Andrew J. Armstrong, Antoine Thiery-Vuillemin, Mototsugu Oya, Eugenia Loredo, Giuseppe Procopio, Juliana Janoski de Menezes, 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).” In Journal of Clinical Oncology, 40:11–11. American Society of Clinical Oncology (ASCO), 2022. https://doi.org/10.1200/jco.2022.40.6_suppl.011.
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). In: Journal of Clinical Oncology. American Society of Clinical Oncology (ASCO); 2022. p. 11–11.
Saad, Fred, 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).Journal of Clinical Oncology, vol. 40, no. 6_suppl, American Society of Clinical Oncology (ASCO), 2022, pp. 11–11. Crossref, doi:10.1200/jco.2022.40.6_suppl.011.
Saad F, Armstrong AJ, Thiery-Vuillemin A, Oya M, Loredo E, Procopio G, Janoski de Menezes J, Girotto GC, Arslan C, Mehra N, Parnis F, Brown E, Schlürmann F, Joung JY, Sugimoto M, Poehlein CH, Harrington E, Desai C, Kang J, Clarke N. 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). Journal of Clinical Oncology. American Society of Clinical Oncology (ASCO); 2022. p. 11–11.

Published In

Journal of Clinical Oncology

DOI

EISSN

1527-7755

ISSN

0732-183X

Publication Date

February 20, 2022

Volume

40

Issue

6_suppl

Start / End Page

11 / 11

Publisher

American Society of Clinical Oncology (ASCO)

Related Subject Headings

  • Oncology & Carcinogenesis
  • 3211 Oncology and carcinogenesis
  • 1112 Oncology and Carcinogenesis
  • 1103 Clinical Sciences