KEY TAKEAWAYS
- The BAYOU trial is a randomized, multicenter, double-blind, phase II trial with the primary aim of assessing the efficacy and safety of durvalumab plus olaparib compared to durvalumab plus placebo in patients with (mUC).
- The trial enrolled untreated, platinum-ineligible patients with mUC, and the patients were randomly assigned to receive either durvalumab plus olaparib or durvalumab plus placebo.
- The results showed that adding olaparib to durvalumab did not improve survival outcomes in an unselected mUC population. Still, there was a potential role for PARP inhibition in patients with UC harboring HRRm.
- Treatment-related grade 3 or 4 adverse events occurred in 18% and 9% of patients.
Most cases of urothelial carcinoma (UC) have mutations in HRRm, making tumor cells vulnerable to poly (ADP-ribose) polymerase (PARP) inhibition. Therefore, Durvalumab (anti-programmed cell death-1 ligand) in combination with olaparib (PARP inhibitor) was studied for its effectiveness and safety in patients with metastatic UC (mUC). Patients with mUC who were not eligible for platinum treatment were enrolled in a randomized, multicenter, double-blind phase II trial. Durvalumab (1,500 mg intravenously every 4 weeks) and olaparib (300 mg orally, twice daily) were compared to durvalumab alone (N = 154) and placebo (N = 152). The researchers determined PFS as the primary endpoint using RECIST 1.1 criteria. Progression-free survival (PFS) and overall survival (all patients) were secondary endpoints.
Overall, the combination of durvalumab and olaparib increased median PFS by 2.2 months (95% CI, 3.6 to 5.6) compared to durvalumab alone (3.5 months; 95% CI, 1.9 to 5.1) (hazard ratio [HR], 0.94; 95% CI, 0.64 to 1.39; log-rank P value,.789). Both groups had similar overall survival rates of 10.2 months (95% CI, 7.0 to 13.9) and 10.7 months (95% CI, 7.2 to 17.3) (HR, 1.07; 95% CI, 0.72 to 1.61), respectively. Median progression-free survival (PFS) was 5.6 months (95% CI, 1.9 to 8.1) in the 20% of patients with HRRm compared to 1.8 months (95% CI, 1.7 to 2.2) in the control group (HR, 0.18; 95% CI, 0.06 to 0.47). Eighteen percent and nine percent of patients experienced treatment-related adverse events in grade 3 or 4.
There was no improvement in survival rates when olaparib was added to durvalumab in an unselected mUC population. Similar efficacy results were seen with durvalumab compared to other anti-apoptotic agents targeting apoptosis-related proteins. Secondary analyses, however, have shown that PARP inhibition may be helpful for UC patients who also carry HRRm.
Source Link: https://pubmed.ncbi.nlm.nih.gov/35737919/
Clinical Link: https://clinicaltrials.gov/ct2/show/NCT03459846
Rosenberg JE, Park SH, Kozlov V, Dao TV, Castellano D, Li JR, Mukherjee SD, Howells K, Dry H, Lanasa MC, Stewart R, Bajorin DF. Durvalumab Plus Olaparib in Previously Untreated, Platinum-Ineligible Patients With Metastatic Urothelial Carcinoma: A Multicenter, Randomized, Phase II Trial (BAYOU). J Clin Oncol. 2023 Jan 1;41(1):43-53. doi: 10.1200/JCO.22.00205. Epub 2022 Jun 23. PMID: 35737919; PMCID: PMC9788981.
