Adjuvant Atezolizumab Shows No Significant Survival Benefit in Residual Triple-Negative Breast Cancer

Adding atezolizumab immunotherapy to capecitabine for the adjuvant treatment of triple-negative breast cancer (TNBC) in patients with residual disease after neoadjuvant chemotherapy does not offer a significant survival benefit, suggested a Korean trial presented at ESMO Breast Cancer 2026. After a median follow-up of 47.4 months, there was no significant difference in invasive disease-free survival between the groups, at a 5-year rate with atezolizumab plus capecitabine of 70.3% vs 66.5% with capecitabine alone, or a hazard ratio of 0.84 (P = .42). There was also no significant difference in overall survival, at a rate of 79.3% at 5 years with combination adjuvant therapy vs 77.1% with capecitabine alone, or a hazard ratio of 0.81 (P = .45).

The MIRINAE trial randomly assigned 280 patients with TNBC with measurable residual disease of at least 1 cm and/or at least one positive lymph node after anthracycline- and taxane-based neoadjuvant chemotherapy to 18 cycles of atezolizumab plus eight cycles of capecitabine (n = 139) or eight cycles of capecitabine alone (n = 141). There was nevertheless a numerical improvement seen in both invasive disease-free and overall survival with atezolizumab plus capecitabine vs capecitabine alone, reaching a trend toward a benefit in patients with tumors positive for PD-L1 expression. In PD-L1-positive patients, the invasive disease-free survival hazard ratio was 0.67 vs 0.92 in PD-L1-negative patients, and the overall survival hazard ratio was 0.57 vs 0.93. As expected, the combination was associated with a higher rate of immune-related adverse events, seen in 38.1% of patients vs 2.8% with capecitabine, with only one grade ≥ 3 immune-related adverse event: a case of type 1 diabetes in the combination arm.

The trial was designed before the results of KEYNOTE-522 were published. That trial showed a benefit from adding pembrolizumab to neoadjuvant chemotherapy in this setting, leading to the FDA granting approval in 2021 to pembrolizumab in combination with chemotherapy for neoadjuvant treatment, continued as a single agent for adjuvant treatment, following surgery for patients with high-risk, early-stage TNBC. The CREATE-X trial demonstrated that adjuvant capecitabine improved disease-free survival in this patient population, establishing capecitabine as a standard post-neoadjuvant option. An invited discussant noted that the key message from these findings is that, more or less, they are negative, so immunotherapy in this setting does not provide a clinical benefit.

Separately, a study of 196 patients with metastatic TNBC found significant enrichment of androgen receptor expression in HER2-low compared with HER2-0 disease (mean 33.7% vs 21.4%; P = .038), whereas no significant immunological differences were observed. HER2-low/androgen receptor-positive patients trended towards longer overall survival, highlighting the potential relevance of these biomarkers.

In a clinical scenario discussion, a 52-year-old patient with metastatic TNBC including lung lesions and previously treated stable brain metastases presented for first-line treatment recommendations. The systematic approach begins with PD-L1 status assessment and immunotherapy eligibility evaluation. For PD-L1-positive, immunotherapy-eligible patients, sacituzumab govitecan combined with pembrolizumab represents the preferred approach based on ASCENT-04 data. For PD-L1-negative patients, either Dato-DXd or sacituzumab govitecan monotherapy becomes appropriate, with selection based on side effect profiles, dosing schedules, patient life circumstances, and care goals through shared decision-making discussions. The stable treated brain metastases don't significantly impact treatment selection, given encouraging central nervous system penetration data for antibody-drug conjugates. Both sacituzumab govitecan and Dato-DXd demonstrate some CNS activity. Symptom management for nausea includes adherence to prophylactic anti-nausea regimens for three consistent days, while diarrhea management involves immediate loperamide use with escalation protocols for severe cases.

An evidence review on metastasis-directed therapy and local-regional therapy for patients with metastatic breast cancer concluded that current randomized data do not support the routine use of targeted treatment for patients with oligometastatic/oligoprogressive breast cancer. Locoregional therapy for stage IV de novo breast cancer does not improve overall survival or quality of life. However, special scenarios such as young patients with bone-only metastasis, specifically patients with sternal/mediastinal metastasis, have improved outcome with metastasis-directed therapy. Trimodality therapy has also shown promise in improving overall survival.

A separate initiative described an evidence-based, theory-driven paper planner combined with a digital AI companion (Hope.ai) for patients with metastatic TNBC initiating antibody-drug conjugate therapy. Preliminary patient feedback indicated high acceptability, with patients reporting increased confidence in treatment decisions and improved ability to manage adverse effects. The planner underwent four rounds of iterative design with patient input and was disseminated through patient advocacy group partnerships, community oncology centers, and a digital platform.