Adding olaparib to durvalumab does not improve survival outcomes in patients with previously untreated, platinum-ineligible, metastatic urothelial carcinoma (mUC), according to phase 2 results published in the Journal of Clinical Oncology.
Olaparib plus durvalumab did not improve progression-free survival (PFS) or overall survival (OS), when compared with durvalumab alone, in the overall cohort. However, olaparib-durvalumab did provide a PFS and OS benefit for patients with homologous recombination repair gene mutations (HRRm).
These results come from the phase 2 BAYOU trial (ClinicalTrials.gov identifier: NCT03459846). The trial included 154 patients with untreated, platinum-ineligible mUC. Patients were randomly assigned to receive durvalumab (1500 mg intravenously, once every 4 weeks) plus olaparib (300 mg orally, twice daily) or durvalumab plus placebo.
There were 78 patients in the olaparib-durvalumab arm (median age, 79 years; range, 47-89) and 76 patients in the placebo-durvalumab arm (median age, 72 years; range, 45-88). In both arms, 72% of patients were men, and most patients were White or Asian (approximately 50% each). HRRm were present in 21.8% of patients in the olaparib-durvalumab arm and 18.4% of those in the placebo-durvalumab arm.
The median PFS and OS were not significantly different between the treatment arms. The median PFS was 4.2 months in the olaparib-durvalumab arm and 3.5 months in the placebo-durvalumab arm (hazard ratio [HR], 0.94; 95% CI, 0.64-1.39; P =.789). The median OS was 10.2 months and 10.7 months, respectively (HR, 1.07; 95% CI, 0.72-1.61; P =.728).
However, researchers observed an improvement in PFS and OS with olaparib among patients with HRRm. The median PFS was 5.6 months in the olaparib-durvalumab arm and 1.8 months in the placebo-durvalumab arm (HR, 0.18; 95% CI, 0.06-0.47; P <.001). The median OS was 8.6 months and 5.8 months, respectively (HR, 0.56; 95% CI, 0.25-1.23).
“The results of the BAYOU study suggest a potential role for PARP inhibitors in the treatment of mUC with HRRm, and further investigation is warranted in both platinum-eligible and platinum-ineligible patients,” the researchers wrote.
Treatment-related adverse events (TRAEs) occurred in 72.4% of patients in the olaparib-durvalumab arm and 60.5% of those in the placebo-durvalumab arm. The rate of grade 3-4 TRAEs was 18.4% and 9.2%, respectively.
The most common TRAE in both arms was anemia. It occurred in 23.7% of patients in the olaparib-durvalumab arm and 13.2% of those in the placebo-durvalumab arm.
Disclosures: This research was supported by AstraZeneca. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.
Rosenberg JE, Park SH, Kozlov V, et al. Durvalumab plus olaparib in previously untreated, platinum-ineligible patients with metastatic urothelial carcinoma: A multicenter, randomized, phase II trial (BAYOU). J Clin Oncol. Published online June 23, 2022. doi:10.1200/JCO.22.00205