Editor’s Note: The 2025 ASCO annual meeting was held from May 30 to June 3 in Chicago, USA. At this annual meeting, a number of research results carried out by Professor Binghe Xu 's team from Cancer Hospital, Chinese Academy of Medical Sciences were presented.One study in particular compares the efficacy of TQB2450 (Benmelstobart) combined with anlotinib versus albumin-bound paclitaxel as first-line therapy in patients with recurrent or metastatic triple-negative breast cancer (TNBC). The results show that the combination group demonstrated a favorable trend in both progression-free survival (PFS) and overall survival (OS), with manageable adverse events, offering a promising chemotherapy-free treatment option for TNBC patients. Oncology Frontier spoke with Prof. Jiayu Wang, first author of the study, to learn more about the clinical design and implications.Study Overview
Background: Recurrent or metastatic TNBC is a highly aggressive malignancy with poor prognosis. Benmelstobart (TQB2450) is a humanized anti–PD-L1 monoclonal antibody, while anlotinib is an oral multi-targeted tyrosine kinase inhibitor with anti-angiogenic activity. This combination has shown synergistic effects in indications such as small cell lung cancer, endometrial cancer, and renal cell carcinoma. The present randomized, open-label clinical trial evaluates the efficacy of Benmelstobart plus anlotinib versus albumin-bound paclitaxel as first-line treatment in recurrent/metastatic TNBC.
Methods: The study originally planned to enroll 332 patients. The first patient was enrolled in July 2020; however, due to slow accrual, enrollment was closed in January 2023. Treatment-naïve patients with stage IV or recurrent/metastatic TNBC were randomized 1:1 into two groups. The treatment group received 1200 mg Benmelstobart via IV infusion on day 1, plus 12 mg anlotinib orally on days 1–14 of a 21-day cycle. The control group received 100 mg/m² albumin-bound paclitaxel IV on days 1, 8, and 15 of a 28-day cycle. Randomization was stratified based on prior exposure to taxane-based therapy in the neoadjuvant/adjuvant setting and baseline liver/brain metastasis. The primary endpoint was PFS assessed by an independent blinded review committee per RECIST 1.1 criteria .
Results:
A total of 147 patients were randomized: 75 in the combination therapy group and 72 in the control group. In the intention-to-treat analysis, the median PFS in the combination group was 7.85 months versus 5.55 months in the control group (HR = 0.70; 95% CI: 0.46–1.06; P = 0.1687) .
Median OS was 35.81 months in the combination group compared to 21.03 months in the control group (HR = 0.78; 95% CI: 0.49–1.24; P = 0.2625) . Grade ≥3 treatment-related adverse events occurred in 56.5% of patients in the combination group and 36.6% in the control group. The most common grade ≥3 AEs in the combination group were hypertension (28.0%) and hypertriglyceridemia (13.3%).
Conclusion: Benmelstobart combined with anlotinib demonstrated a trend toward prolonged PFS and OS compared with albumin-bound paclitaxel in the first-line treatment of recurrent/metastatic TNBC. Adverse events were consistent with the known safety profiles of both agents.
Investigator Commentary
At the time this study was initiated in mid-2020, chemotherapy remained the primary standard of care for first-line TNBC, given the lack of effective targeted therapies. Although PD-1/PD-L1 inhibitors in combination with chemotherapy have shown benefit in some patients (e.g., PD-L1–positive), many others fail to respond. To explore chemotherapy-free approaches, a phase Ib study previously evaluated Benmelstobart plus anlotinib in second-line and later-line TNBC, achieving an ORR of 26.5% and median PFS of 5.6 months, demonstrating preliminary efficacy and safety of the regimen.
To further assess this combination as a first-line treatment, we launched this randomized trial. Although the planned sample size was not reached, the results suggest a favorable trend in both PFS and OS for the combination group, with consistent benefits observed across multiple subgroups. While the data did not reach statistical significance, the hazard ratio (HR) trends indicate a potential survival advantage—particularly in OS, where the median of 35.81 months is quite encouraging.
However, the study does have limitations, including small sample size and a relatively short follow-up of around 18 months, which may limit the robustness of conclusions. Future efforts should focus on expanding sample size, extending follow-up, and exploring predictive biomarkers for response to better stratify patients. Further mechanistic studies are also needed to clarify how anti-angiogenic therapy synergizes with immunotherapy and to optimize combination strategies.
- Medical Oncologist
- Tenured Professor, Peking Union Medical College
- Director, Clinical Research Center for Drug Trials, Cancer Hospital, Chinese Academy of Medical Sciences
- MD, PhD, Chief Physician, Master’s Supervisor
- Department of Medical Oncology, Cancer Hospital, Chinese Academy of Medical Sciences
