At the 2026 ASCO Annual Meeting, Fumikata Hara and colleagues presented results from the phase 3 JCOG1919E (AMBITION) trial evaluating whether the addition of atezolizumab to paclitaxel plus bevacizumab could improve outcomes in patients with hormone receptor-positive/HER2-negative (HR+/HER2−) advanced breast cancer.
HR+/HER2− breast cancer is generally considered an immunologically “cold” tumor type and has historically demonstrated limited responsiveness to immune checkpoint blockade. Because VEGF-mediated angiogenesis contributes to an immunosuppressive tumor microenvironment, investigators hypothesized that bevacizumab-mediated VEGF inhibition might enhance sensitivity to anti–PD-L1 therapy.
Study Design and Treatment
JCOG1919E AMBITION was a multicenter, open-label, randomized controlled phase III trial.
Eligible patients had HR-positive/HER2-negative unresectable locally advanced, recurrent, or stage IV breast cancer. Patients were required to have measurable disease, ECOG performance status 0–2, and no prior chemotherapy for advanced disease. Patients were endocrine-resistant or had life-threatening visceral metastases.
A total of 281 patients were randomized 1:1 to receive:
- Arm A: paclitaxel plus bevacizumab
- Arm B: paclitaxel plus bevacizumab plus atezolizumab
Treatment was given in 28-day cycles.
Arm A received paclitaxel 90 mg/m² on days 1, 8, and 15 plus bevacizumab 10 mg/kg on days 1 and 15.
Arm B received paclitaxel 90 mg/m² on days 1, 8, and 15 plus bevacizumab 10 mg/kg on days 1 and 15 plus atezolizumab 840 mg on days 1 and 15.
Randomization was stratified by recurrence versus stage IV disease, presence versus absence of liver metastases, and PD-L1 immune-cell expression assessed using the VENTANA SP142 assay.
The primary endpoint was investigator-assessed progression-free survival according to RECIST version 1.1.
Secondary endpoints included overall survival, blinded independent central review-assessed PFS, objective response rate, duration of response, and safety.
Progression-Free Survival
The addition of atezolizumab to paclitaxel plus bevacizumab did not significantly improve investigator-assessed progression-free survival.
Median investigator-assessed PFS was:
- 12.4 months with paclitaxel, bevacizumab, and atezolizumab
- 11.2 months with paclitaxel and bevacizumab
The hazard ratio was 0.876, with a 95% CI of 0.670–1.145 and a P value of 0.168.
Therefore, the primary endpoint was not met.
By blinded independent central review, median PFS was:
- 16.7 months with paclitaxel, bevacizumab, and atezolizumab
- 13.8 months with paclitaxel and bevacizumab
The hazard ratio was 0.919, with a 95% CI of 0.678–1.246 and a P value of 0.294.
Overall Survival
A numerical improvement in overall survival was observed with the atezolizumab-containing regimen.
Median overall survival was:
- 39.1 months with paclitaxel, bevacizumab, and atezolizumab
- 31.2 months with paclitaxel and bevacizumab
The hazard ratio was 0.804, with a 95% CI of 0.584–1.108 and a P value of 0.091.
Safety
The safety profile was consistent with the known profile of each agent. Immune-mediated events occurred more frequently with atezolizumab but were largely manageable.
Key Safety Results
- Grade ≥3 adverse events were similar between treatment arms
- The most common immune-related adverse events with atezolizumab were rash (17.3%), adrenal insufficiency
- (11.5%), and hypothyroidism (10.8%)
- No treatment-related deaths were reported
- No new safety signals emerged during the study
Conclusion
The phase III JCOG1919E AMBITION trial did not meet its primary endpoint. The addition of atezolizumab to paclitaxel plus bevacizumab did not significantly improve investigator-assessed progression-free survival in patients with HR-positive/HER2-negative advanced breast cancer.
Although a numerical improvement in overall survival was observed, these results do not support the routine addition of atezolizumab to paclitaxel plus bevacizumab in an unselected HR-positive/HER2-negative advanced breast cancer population.
