KEY TAKEAWAYS
- The A-Brave phase 3 trial aimed to investigate the efficacy of avelumab as an adjuvant treatment for high-risk early TNBC.
- The Co-primary endpoint was to determine DFS, and the secondary endpoint was OS.
- Researchers noticed that Avelumab shows improved OS in high-risk TNBC; further investigation is ongoing.
Prognosis of patients with early triple-negative breast cancer (TNBC), characterized by its poor outcomes, necessitates the exploration of novel therapies. TNBC’s high immunogenicity suggests potential sensitivity to immune checkpoint inhibitors. The A-BRAVE trial was initiated to evaluate avelumab, an anti-PD-L1 antibody, as adjuvant therapy for patients with early TNBC at high risk.
Pier Franco Conte and the team aimed to assess the efficacy of avelumab in this context.
They performed an inclusive analysis for a phase III, multicentric, randomized adjuvant study comparing 1 year of treatment with the anti-PD-L1 avelumab versus observation for patients with TNBC considered at high risk of relapse.
Patients were enrolled following completion of standard curative-intent treatment, including surgery and neoadjuvant/adjuvant chemotherapy. High risk was defined as invasive residual disease after neoadjuvant chemotherapy (Stratum A), 2) >pN2/any pT, pN1/pT2, or pN0/pT3 after primary surgery (Stratum B).
Patients were randomly assigned (1:1, balanced for strata A and B) to receive Avelumab 10 mg/kg I.V. every 2 weeks for 1 year or observation. Co-primary endpoints were disease-free survival (DFS) in the total population and Stratum A. The study aimed to detect an improvement in the 3-year DFS rate (HR 0.6; 90% power, 1-sided test, alfa 2%) from 60% to 73.6% with 474 patients, with 172 DFS events required for event-driven analysis. Overall survival (OS) was a secondary endpoint.
From June 2016 to October 2020, 477 patients were randomly assigned from 64 Italian and 6 UK centers. After that, about 11 patients (3 receiving avelumab, 8 in the control group) withdrew consent immediately after randomization and were excluded from further analyses. Three hundred seventy-eight patients entered Stratum A (83%), with 99 (57 receiving avelumab, 42 in the control group) receiving additional chemotherapy after surgery prior to trial enrollment.
The study concluded that 1 year of adjuvant avelumab versus control did not significantly improve DFS in patients with high-risk TNBC. However, the secondary endpoint of OS was significantly improved with avelumab compared to the control. Results for relapse-free survival (RFS) and distant metastasis-free survival (DMFS) will also be reported. Additionally, a centralized collection of tumor tissue, plasma, and feces has been conducted, enabling various correlative studies.
The study was sponsored by the Istituto Oncologico Veneto IRCCS.
Source: https://meetings.asco.org/abstracts-presentations/232429
Clinical Trial: https://clinicaltrials.gov/study/NCT02926196
Conte P F, Dieci M V, Bisagni G. et al. (2024). “A-BRAVE trial: A phase III randomized trial with avelumab in early triple-negative breast cancer with residual disease after neoadjuvant chemotherapy or at high risk after primary surgery and adjuvant chemotherapy.” Presented at ASCO 2024. J Clin Oncol 42, 2024 (suppl 17; abstr LBA500), 10.1200/JCO.2024.42.17_suppl.LBA500
