Addition of Cediranib to Olaparib for Metastatic Castration-Resistant Prostate Cancer

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As reported in the Journal of Clinical Oncology by Kim et al, the phase II National Cancer Institute 9984 trial has shown prolonged radiographic progression-free survival with the addition of cediranib to olaparib in patients with metastatic castration-resistant prostate cancer.


  • Cediranib/olaparib significantly prolonged radiographic progression-free survival vs olaparib alone.
  • The combination was associated with a higher rate of grade 3 and 4 adverse events.

Study Details

In the open-label multicenter trial, 90 patients were randomly assigned between August 2017 and February 2019 to receive cediranib at 30 mg once daily plus olaparib at 200 mg twice daily (n = 45) or olaparib at 300 mg twice daily (n = 45).

The primary endpoint was radiographic progression-free survival in the intention-to-treat population.

Progression-Free Survival

Median follow-up was 26.1 months. Median radiographic progression-free survival was 8.5 months (95% confidence interval [CI] = 5.4–12.0 months) in the combination group vs 4.0 months (95% CI = 3.2–8.5 months) in the control group (hazard ratio [HR] = 0.617, 95% CI = 0.392–0.969, P = .0359).

In subgroup analyses, median radiographic progression-free survival with the combination vs olaparib was:

  • 10.6 months (95% CI = 5.9 months to not evaluable) vs 3.8 months (95% CI = 2.33 months to not evaluable) among 12 vs 14 patients with homologous recombination repair (HRR)-deficient disease (HR = 0.64, 95% CI = 0.27–1.50)
  • 5.5 months (95% CI = 3.73–11.77 months) vs 4.0 months (95% CI = 3.73–8.47 months) among 29 vs 29 patients with HRR-proficient disease (HR = 0.75, 95% CI = 0.45–1.35)
  • 13.8 months (95% CI = 3.3 months to not evaluable) vs 11.3 months (95% CI = 3.8 months to not evaluable) among 9 vs 7 patients with a BRCA2 mutation (HR = 0.98, 95% CI = 0.32–2.99).  

Adverse Events

Grade 3 or 4 adverse events occurred in 61% of patients in the cediranib/olaparib group vs 18% of those in the olaparib group. Dose reduction due to adverse events occurred in 84% vs 36% of patients. No cases of acute myeloid leukemia or myelodysplastic syndrome were observed. One death in the combination group—due to intracranial hemorrhage—was considered related to treatment.

The investigators concluded, “Cediranib combined with olaparib improved radiographic progression-free survival compared with olaparib alone in men with metastatic castration-resistant prostate cancer. This combination was associated with an increased incidence of grades 3 [and] 4 adverse events. BRCA2-mutated subgroups treated with olaparib with or without cediranib were associated with a numerically longer median radiographic progression-free survival.”

Joseph W. Kim, MD, of the Department of Medical Oncology, Yale School of Medicine, and Yale Cancer Center, is the corresponding author for the Journal of Clinical Oncology article.

Disclosure: The study was supported by the Cancer Therapy Evaluation Program (CTEP) of the National Cancer Institute. For full disclosures of the study authors, visit

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