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Randomized Trial of Olaparib With or Without Cediranib for Metastatic Castration-Resistant Prostate Cancer: The

Joseph W Kim1, Rana R McKay2, Marc R Radke3

  • 1Medical Oncology Yale School of Medicine and Yale Cancer Center, New Haven, CT.

Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
|October 18, 2022
PubMed
Abstract

Insights

Cediranib combined with olaparib improved radiographic progression-free survival in men with metastatic castration-resistant prostate cancer. While effective, this combination led to more severe adverse events compared to olaparib alone.

Area of Science:

  • Oncology
  • Pharmacology
  • Genitourinary Cancer Research

Background:

  • Cediranib, a vascular endothelial growth factor receptor inhibitor, shows preclinical promise in sensitizing tumors to poly-(ADP-ribose) polymerase inhibitors.
  • Homologous recombination repair (HRR) gene expression is suppressed by cediranib, potentially enhancing cancer treatment efficacy.

Purpose of the Study:

  • To evaluate the efficacy of combining cediranib with olaparib in patients with metastatic castration-resistant prostate cancer (mCRPC).
  • To assess the impact of cediranib and olaparib combination therapy on radiographic progression-free survival (rPFS).

Main Methods:

  • A randomized trial comparing cediranib plus olaparib versus olaparib alone in patients with progressive mCRPC.
  • Primary endpoint: radiographic progression-free survival (rPFS) in the intention-to-treat population.
  • Secondary endpoints included rPFS in HRR-deficient and HRR-proficient subgroups, including BRCA2-mutated patients.

Main Results:

  • The combination of cediranib and olaparib significantly improved median rPFS (8.5 months) compared to olaparib alone (4.0 months) in the overall mCRPC population (HR, 0.617; P = .0359).
  • In HRR-deficient patients, median rPFS was 10.6 months with cediranib/olaparib versus 3.8 months with olaparib alone.
  • Grade 3-4 adverse events were more frequent in the cediranib/olaparib arm (61%) compared to the olaparib alone arm (18%).

Conclusions:

  • Cediranib combined with olaparib demonstrates improved rPFS in men with mCRPC compared to olaparib monotherapy.
  • The combination therapy is associated with a higher incidence of severe adverse events.
  • A numerically longer median rPFS was observed in BRCA2-mutated subgroups treated with olaparib, with or without cediranib.

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