Pierfranco Conte, MD, on Early-Stage Triple-Negative Breast Cancer: Trial Update on Avelumab as Adjuvant Treatment

The A-BRAVE trial was an academic driven trial conducted in patients at high risk with early triple negative breast cancer. The purpose of the study was to improve the prognosis of these patients by selecting subgroup of patients at particularly high risk of relapse. In the study, we have randomized two strata of patients. One was patients who went to surgery upfront, and after surgery had a diagnosis of advanced stages of disease, high positivity, axillary lymph load, large tumor size. The second stratum were the patients who had received neoadjuvant chemotherapy and had surgery after neoadjuvant chemotherapy, still had invasive residual disease in the breast and/or in the axillary lymph nodes. The primary end points of the study were disease-free survival in the entire study population, and the disease-free survival in the post-neoadjuvant group, which included 82% of a total population. We didn't meet the primary end points, because we did observe a difference in favor of avelumab in disease-free survival, a 5% improvement at three years in disease-free survival in the whole population, and a 6% improvement in the post-neoadjuvant population. But this was not statistically significant, hazard ratio was 0.8, p-value 0.17. We did observe on the contrary, a statistically significant difference in overall survival in the entire study. Population at three years the advantage in overall survival for Avelumab was 8.5%, the hazard ratio 0.66, which means a 34% reduction in the risk of death, the p-value 0.035. We did also perform a postdoc exploratory analysis, try to understand why we are seeing a larger benefit in overall survival than disease-free survival, and the analysis was on distant disease-free survival. And again, we did observe a significant advantage for Avelumab, 7.5% improvement at three years in distant disease-free survival, hazard ratio 0.7, p-value 0.027. We do know that in many countries today standard of care for high-risk, early triple negative disease is neoadjuvant chemotherapy plus Pembrolizumab. So Pembrolizumab is given to all these patients before surgery, and also is continued after surgery, independently from the pathological response observed at surgery. And this is, as I said before, standard recommended by international and also national guidelines in Italy. There are aware still patients who do not receive Pembro if a neoadjuvant situation. Patients who have a smaller tumor size, clinically negative axillary lymph nodes, patients for whom physicians may, or might, have some concern about the tolerability of a treatment. So there are still patients who receive neoadjuvant chemotherapy without Pembro. Many of these patients fortunately receive a pathological [inaudible 00:04:00] response, but still some of them, 40 to 50%, have residual invasive disease, and they think that for these patients avelumab will be a good option. Highly effective in terms of distant disease-free survival, effective in terms of overall survival, and also tolerability was quite good. Now of course, this is the first presentation of the study, because the study was an event-driven study. We will follow up the patients longer, by sure. And there are many translational studies ongoing, because we have collected tumor samples, blood, plasma, and feces by all these patients. So, we will have a lot of translational research trying to understand who are the patients who benefit more, and who are the patients who unfortunately still relapse in spite of avelumab?