KEY TAKEAWAYS
- BROCADE3 is a phase 3 trial investigating veliparib in combination with carboplatin/paclitaxel for BRCA-mutated advanced breast cancer
- The study aimed to establish the exposure-response relationship for veliparib in this patient population.
- The exposure-efficacy analysis showed a significant benefit of veliparib monotherapy compared to placebo monotherapy, while the use of adding veliparib to carboplatin/paclitaxel was modest and non-significant
- The exposure-safety analysis did not reveal any exposure-dependent trend in adverse events.
The BROCADE3 trial is a phase 3 study that aimed to evaluate the effectiveness of veliparib in combination with carboplatin/paclitaxel and as monotherapy in patients with advanced breast cancer who have germline BRCA1/2 mutations and are human epidermal growth factor receptor 2-negative. The current analysis focused on characterizing the relationship between veliparib exposure and its effectiveness and safety in this patient population. The study included exposure-efficacy comments of progression-free survival using Kaplan-Meier plots and Cox proportional hazards models. The results showed a statistically significant benefit of veliparib monotherapy compared to placebo (hazard ratio, 0.49; 95%CI, 0.33-0.73) and a modest, non-statistically significant benefit (hazard ratio, 0.81; 95%CI, 0.62-1.05) of adding veliparib to carboplatin/paclitaxel.
By including exposure as a time-varying predictor in the Cox proportional hazards model, it was determined that the relationship between veliparib exposure and progression-free survival (PFS) remained constant when veliparib was administered with carboplatin/paclitaxel or as monotherapy. An analysis of vulnerability and safety did not reveal any notable trends in the incidence of exposure-related adverse events. These results support using 300–400 mg of veliparib twice daily as monotherapy if carboplatin/paclitaxel is stopped before the disease progresses in this patient population and the use of 120 mg of veliparib twice daily in conjunction with carboplatin/paclitaxel.
Source:https://pubmed.ncbi.nlm.nih.gov/35403245/
Clinical Trial: https://clinicaltrials.gov/ct2/show/NCT02163694/
Stodtmann S, Eckert D, Joshi R, Nuthalapati S, Ratajczak CK, Menon R, Mensing S, Xiong H. Exposure-Response Model With Time-Varying Predictors to Estimate the Effects of Veliparib in Combination With Carboplatin/Paclitaxel and as Monotherapy: Veliparib Phase 3 Study in BRCA-Mutated Advanced Breast Cancer (BROCADE3) Trial. J Clin Pharmacol. 2022 Oct;62(10):1236-1246. doi 10.1002/jcph.2061. Epub 2022 May 5. PMID: 35403245.
