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1357O Biomarker Analysis and Updated Results from the Phase III PROpel Trial of Abiraterone (Abi) and Olaparib (Ola) vs Abi and Placebo (Pbo) as First-Line (1L) Therapy for Patients (Pts) with Metastatic Castration-Resistant Prostate Cancer (mCRPC)

Background: At the primary analysis of PROpel (NCT03732820; data cut-off [DCO]: 30/07/21), abi + ola significantly prolonged radiographic progression-free survival (rPFS) vs pbo + abi in 1L mCRPC (HR 0.66, 95% CI 0.54–0.81; P<0.0001). Overall survival (OS) trended towards a benefit with abi + ola vs abi + pbo (28.6% maturity; HR 0.86, 95% CI 0.66–1.12). We report biomarker analysis from the primary analysis and updated overall survival and safety data from a planned OS interim analysis (DCO2).

Methods: PROpel is a double-blind, pbo-controlled trial. 796 pts were randomized 1:1 to ola (300 mg twice daily [bid]) or pbo, and abi (1000 mg once daily) + prednisone or prednisolone (5 mg bid), irrespective of homologous recombination repair gene mutation (HRRm) status. The primary endpoint was rPFS by investigator assessment. OS was a key secondary endpoint. Aggregated results from tumour tissue (FoundationOne®CDx) and circulating tumour DNA (FoundationOne®Liquid CDx) tests were used to classify pts HRRm status.

Results: Pts with HRRm, including BRCAm, were balanced between treatment arms and rPFS favoured abi + ola for all biomarker subgroups, including pts with non-HRRm, HRRm and BRCAm status (HR 0.76, 0.50 and 0.23 respectively; Table). Sensitivity analysis of rPFS by blinded independent central review was consistent. At DCO2 (14/03/22) rPFS was consistent with the primary analysis (25.0 vs 16.4 months; HR 0.67, 95% CI 0.56–0.81). A trend towards improved OS with abi + ola vs abi + pbo continued (maturity 40%; HR 0.83; 95% CI 0.66–1.03). Safety and tolerability results remained stable.

Conclusions: Meaningful rPFS improvement of ≥5 months was observed with abi + ola vs abi + pbo in all assessed biomarker subgroups. Updated results show a continuing trend towards improved OS and support a superior clinical benefit with abi + ola vs abi + pbo as 1L therapy for pts with mCRPC.

F. Saad1 A.J. Armstrong2 A. Thiery-Vuillemin3 M. Oya4 N.D. Shore5 G. Procopio6 C. Arslan7 N. Mehra8 F. Parnis9 E. Brown10 F. Constans Schlurmann11 J.Y. Joung12 M. Sugimoto13 O. Sartor14 Y-
Z. Liu15 C.H. Poehlein16 C. Desai17 P.M.D. Del Rosario17 N. Clarke18

  1. Department of Urology, Centre Hospitalier de l’Université de Montréal/CRCHUM, Université de Montreal, Montreal, QC, Canada
  2. Department of Medicine, Duke Cancer Institute Center, Durham, NC, USA
  3. Medical Oncology Department, CHRU Besançon Hôpital J.Minjoz, Besancon, France
  4. Department of Urology, Keio University School of Medicine, Tokyo, Japan
  5. Surgery and Oncology, Carolina Urologic Research Center, Myrtle Beach, SC, USA
  6. Medical Oncology Department, Istituto Nazionale per Cura Tumori Milano, Milan, Italy
  7. Medical Oncology Department, Izmir Economy University Medical Park Hospital, Karsiyaka, Turkey
  8. Medical Oncology Department, Radboud Universitair Medisch Centrum, Nijmegen, Netherlands
  9. Medical Oncology Department, Ashford Cancer Centre Research, Kurralta Park, SA, Australia
  10. Medical Oncology Department, University Hospital Southampton, Southampton, UK
  11. Medical Oncology Department, Centre Hospitalier de Cornouaille, Quimper, France
  12. Center for Urological Cancer, National Cancer Center, Goyang-si, Republic of Korea
  13. Urology Department, Kagawa University Hospital, Kagawa, Japan
  14. Hematology/Oncology Department, Tulane Cancer Center, New Orleans, LA, USA
  15. Precision Medicine, Oncology R&D, Astrazeneca, Cambridge, UK
  16. Clinical Research, Merck & Co., Inc., Rahway, NJ, USA
  17. Global Medicines Development, Oncology R&D, AstraZeneca, Cambridge, UK
  18. Department of Urology, The Christie and Salford Royal NHS Foundation Trusts, Manchester, UK
Source: Saad F. Armstrong AJ. Thiery-Vuillemin A. et al. "1357O Biomarker Analysis and Updated Results from the Phase III PROpel Trial of Abiraterone (Abi) and Olaparib (Ola) vs Abi and Placebo (Pbo) as First-Line (1L) Therapy for Patients (Pts) with Metastatic Castration-Resistant Prostate Cancer (mCRPC)." Annals of Oncology. 2022. 33, 7, S1160.