Dr Geyer on the Efficacy of Perioperative Atezolizumab Plus Chemotherapy in Stage II/III TNBC

“Disappointingly, the study did not meet its primary end point of EFS…[However,] there’s always been the question with the checkpoint inhibitors [regarding] which subsets of patients clearly benefit [and for whom] exposure to the potential toxicities is worth it…we’re still going to look carefully at that to see if [our study] could at least inform the field about the [use of] checkpoint inhibitors.”

Charles E. Geyer, Jr., MD, professor, medicine, University of Pittsburgh Medical Center (UPMC); interim division chief, Malignant Hematology and Medical Oncology, Department of Medicine, UPMC Hillman Cancer Center, discusses the efficacy and safety of neoadjuvant chemotherapy in combination with atezolizumab (Tecentriq) or placebo followed by adjuvant atezolizumab or placebo in patients with stage II/III triple-negative breast cancer (TNBC), according to findings from the phase 3 NSABP B-59/GBG 96-GeparDouze trial (NCT03281954).

Results presented at the 2024 San Antonio Breast Cancer Symposium showed that the addition of atezolizumab to neoadjuvant chemotherapy, followed by adjuvant atezolizumab, did not result in a statistically significant improvement in event-free survival (EFS) compared with neoadjuvant chemotherapy plus placebo, failing to meet the study’sprimary end point (HR, 0.8; 95% CI, 0.62-1.03; log-rank P = 0.08), Geyer begins. The study was powered to demonstrate a hazard ratio of 0.7 or better as evidence of efficacy. The 4-year EFS rate was 85.2% for the atezolizumab arm (n = 773) and 81.9% for the control arm (n = 777), indicating that the addition of atezolizumab provided a marginal increase in EFS but that the difference was not statistically significant and did not achieve clinical relevance for the overall patient population, he explains. The safety profile of atezolizumab in combination with multiagent chemotherapy was consistent with the known safety profiles observed with these agents in TNBC.

A notable finding from the study was the heterogeneity observed in the forest plots when evaluating specific subsets of patients, Geyer continues. For instance, patients who were clinically node positive, either based on abnormal imaging or confirmed biopsy findings, appeared to derive benefit from the addition of atezolizumab, according to Geyer. In contrast, patients with node-negative disease did not have a benefit, he reports. Similar trends were observed when patients were stratified by tumor size and the presence of tumor-infiltrating lymphocytes, indicating potential patient subgroups that may benefit from checkpoint inhibition, Geyer details. This highlights the importance of conducting further translational studies to identify biomarkers that could predict which patients are most likely to benefit from adding checkpoint inhibitors to neoadjuvant or adjuvant therapy in TNBC, he says.

Although the primary efficacy end point was not met, the findings from this trial contribute to the ongoing exploration of checkpoint inhibitors in TNBC, Geyer emphasizes. Pembrolizumab (Keytruda) remains the standard PD-1 inhibitor in this setting but these results provide valuable insights into the potential for biomarker-driven treatment approaches to refine patient selection for checkpoint inhibitor therapy, Geyer concludes.