Atezolizumab (Tecentriq) in combination with chemotherapy failed to demonstrate a significant improvement in event-free survival (EFS) for patients with triple-negative breast cancer (TNBC), according to results from the phase 3 NSABP B-59/GBG-96-GeparDouze trial presented at the 2024 San Antonio Breast Cancer Symposium. The study, which randomized 1550 patients, found that the addition of perioperative atezolizumab to neoadjuvant chemotherapy followed by adjuvant atezolizumab did not meet its primary endpoint.
At a median follow-up of 46.9 months, the 4-year EFS rate was 85.2% (95% CI, 82.4%-87.7%) in the atezolizumab/chemotherapy arm compared to 81.9% (95% CI, 78.9%-84.6%) in the placebo/chemotherapy arm. This difference was not statistically significant (HR, 0.8; 95% CI, 0.62-1.03; P = .08). According to presenting author Charles Geyer, MD, University of Pittsburgh Medical Center, this lack of benefit was consistent across all patient subgroups with the exception of clinical nodal status, in which patients with positive node status showed a significant difference favoring atezolizumab (P = .039).
Impact on Overall Survival and Pathological Complete Response
While the trial did not meet its primary endpoint of improved EFS, researchers observed that the addition of atezolizumab to neoadjuvant chemotherapy did increase the pathological complete response (pCR) rate to 63%, compared to 57% with placebo. However, this did not translate into a statistically significant overall survival (OS) benefit at 4 years, with rates of 90.2% (95% CI, 87.7%-92.3%) and 89.5% (95% CI, 86.9%-91.5%) in the atezolizumab and placebo arms, respectively (HR, 0.86; 95% CI, 0.62-1.19).
Safety Profile
The safety analysis, which included 1532 patients, revealed similar rates of treatment-emergent adverse events (TEAEs) between the two arms. Nearly all patients experienced at least one TEAE, with 74.3% experiencing grade 3/4 TEAEs and 32.7% experiencing serious TEAEs. Discontinuation rates due to TEAEs were also comparable, with slight variations across different chemotherapy agents. TEAEs were considered the cause of death for 2 patients in the atezolizumab arm and 3 patients in the placebo arm.
Trial Design and Patient Population
The double-blind NSABP B-59/GBG-96-GeparDouze trial enrolled 1550 patients with centrally confirmed triple-negative breast cancer. The patient characteristics were well-balanced between the study arms. The median age was 49 years (range, 22-79), and the majority of patients were female (99%) and white (90%). Forty-one percent of patients were node-positive, and tumor sizes varied, with 59% between 1.1 and 3.0 cm and 41% greater than 3 cm. PD-L1 status was negative in 64% of patients.
Patients were randomized to receive atezolizumab (1200 mg IV every 3 weeks) or placebo concurrently with paclitaxel (80 mg/m2 IV weekly) for 12 weeks plus carboplatin (AUC of 5 IV for 4 doses), followed by investigator's choice of cyclophosphamide with doxorubicin (AC) or epirubicin (EC) every 2 or 3 weeks for 4 cycles. After surgery, patients continued atezolizumab or placebo as adjuvant therapy for 6 months, along with radiotherapy.
The primary endpoint of the trial was EFS, with secondary endpoints including OS, pCR in the breast and lymph nodes, distant disease-free survival, disease-free survival, and toxicity.
Implications for Future Research
Despite not meeting the primary efficacy endpoint, Dr. Geyer suggested that the results warrant further translational studies to identify potential biomarkers that could help identify subsets of TNBC patients who may benefit from the addition of checkpoint inhibitors to neoadjuvant/adjuvant therapy. These findings highlight the complexity of treating TNBC and the need for more personalized approaches.
