Adding cediranib to olaparib improves radiographic progression-free survival (rPFS) in patients with metastatic castration-resistant prostate cancer (mCRPC), according to a phase 2 trial published in the Journal of Clinical Oncology.
In an intention-to-treat set of 90 patients with progressive mCRPC, the median rPFS was 8.5 months for patients who received olaparib plus cediranib and 4.0 months patients those treated with olaparib alone.
The combination treatment was associated with a 38.3% decreased risk for radiographic progression compared with olaparib alone. The combination arm had a higher incidence of grade 3-4 adverse events than the monotherapy arm (61% vs 18%).
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Patients in the combination arm received olaparib at 200 mg twice daily plus cediranib at 30 mg once daily. Patients in the olaparib-only arm received the drug at a dosage of 300 mg twice daily. The investigators examined treatment effects according to gene biomarker subgroups.
The investigators defined radiographic progression as bone scans showing new lesions compared with baseline, soft tissue progression defined by modified RECIST version 1.1 criteria, and death from any cause.
Descriptive analyses revealed that rPFS was longer in the olaparib-cediranib arm than in the olaparib-only arm among patients with HRR-deficient mCRPC and those with BRCA2-mutated mCRPC, although the differences did not reach statistical significance.
“Unfortunately, the combination of cediranib and olaparib is associated with increased toxicity rates,” the investigators wrote. “Although they were manageable with supportive care, treatment interruptions were frequent. Descriptive analyses of rPFS in biomarker subgroups indicated that a deleterious BRCA2 mutation is the best predictor of olaparib efficacy. Whether cediranib adds any benefit to olaparib in BRCA2-mutated mCRPC remains unclear.”
The investigators acknowledged that a key limitation of their study was that it was not powered for subgroup analyses by biomarkers.
Disclosures: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.
Reference
Kim JW, McKay RR, Radke MR, et al. Randomized trial of olaparib with or without cediranib for metastatic castration-resistant prostate cancer: The results from National Cancer Institute 9984. J Clin Oncol. Published online October 18, 2022. doi:10.1200/JCO.21.02947
