Evaluating the effectiveness and safety of olaparib with or without cediranib in patients with metastatic castration-resistant prostate cancer.

This study evaluated the effectiveness and safety of olaparib (Lynparza) with or without cediranib (Recentin) in patients with metastatic castration-resistant prostate cancer (mCRPC). The data showed that cediranib combined with olaparib significantly improved survival without cancer worsening compared with olaparib alone in these patients. However, the combination was associated with an increased rate of serious side effects.

mCRPC is an aggressive form of PC that has spread beyond the prostate gland and is no longer responsive to hormonal therapy such as androgen deprivation therapy (ADT). ADT reduces the production of androgens (male sex hormones such as testosterone). Reducing these androgens prevents cancer cell growth.

BRCA1 and BRCA2 gene mutations (abnormalities) can be found in many patients with PC. BRCA1/BRCA2 genes block the rapid and uncontrolled growth of cells, therefore the formation of tumors. ATM is a gene that functions as a DNA damage checkpoint. Loss of function of these genes can lead to tumor formation. Targeted therapy is an option for these patients.

Olaparib is a targeted therapy that blocks a protein called PARP, which helps damaged cells to repair themselves. Therefore, PARP inhibitors keep cancer cells from repairing themselves. This eventually causes them to die. BRCA1 and BRCA2 mutated cancers have been shown to be responsive to PARP inhibitors like olaparib. Cediranib is a biological (targeted) therapy that works by blocking the production of new blood vessels needed for tumor growth. Whether cediranib combined with olaparib improves the clinical outcomes in patients with mCRPC is still unknown.

This study involved 90 men with mCRPC. Patients were randomly assigned into two groups. Group 1 included 45 patients who received cediranib (30 mg once daily) plus olaparib (200 mg twice daily). Group 2 included 45 patients who received olaparib (300 mg twice daily) alone. The average follow-up time was 26.1 months.

The average survival without cancer worsening on imaging scans was 8.5 months in group 1 versus 4 months in group 2. This difference was statistically significant. Patients in group 1 were 38% more likely to survive without cancer worsening than patients in group 2.

In patients who had mutations in DNA repair genes, the average survival without cancer worsening on scans was 10.6 months in group 1 versus 3.8 months in group 2. This difference was statistically significant. In patients who had mutations in the BRCA2 gene, the average survival without cancer worsening was 13.8 months in group 1 versus 11.3 months in group 2.

The rate of serious side effects was 61% in group 1 versus 18% in group 2. 

This study concluded that cediranib combined with olaparib significantly improved survival without cancer worsening compared with olaparib alone in men with mCRPC. However, the combination was associated with an increased rate of serious side effects.

This study was funded by AstraZeneca, the manufacturer of cediranib and olaparib. The sample size was very small. Larger studies are needed.