Immunotherapy Plus T-DXd Shows Strong Results in HER2-Low Breast Cancer
The BEGONIA trial finds durvalumab combined with trastuzumab deruxtecan achieves 62% response rate in hard-to-treat metastatic breast cancer.
Summary
A phase 1b/2 clinical trial tested combining durvalumab, an immunotherapy drug, with trastuzumab deruxtecan (T-DXd), a targeted antibody-drug conjugate, as a first-line treatment for women with hormone-receptor-negative, HER2-low metastatic or locally advanced breast cancer. Fifty-eight women were enrolled and treated every three weeks. The combination achieved a 62% objective response rate, with responses lasting a median of over 15 months. Median progression-free survival reached 12.6 months and overall survival reached 30.3 months. While the trial did not hit its predefined response benchmark, the results are considered clinically meaningful for a difficult-to-treat breast cancer subtype. The safety profile matched what is known from each drug individually, though lung inflammation occurred in about one in five patients.
Detailed Summary
Advanced breast cancer remains one of oncology's most challenging problems, particularly for patients whose tumors are hormone-receptor-negative and express only low levels of HER2 — a subgroup historically lacking effective targeted options. This trial aimed to determine whether combining immunotherapy with a next-generation antibody-drug conjugate could improve outcomes for these patients.
The BEGONIA platform trial enrolled 58 women with locally advanced unresectable or metastatic hormone-receptor-negative, HER2-low breast cancer who had not previously received systemic therapy. Participants received durvalumab, an anti-PD-L1 checkpoint inhibitor, plus trastuzumab deruxtecan (T-DXd) every three weeks. Primary endpoints were objective response rate and safety, with duration of response, progression-free survival, and overall survival as secondary endpoints.
The combination produced an objective response rate of 62.1%, falling just short of the protocol-specified benchmark of 66.6%. However, responses were durable: median duration of response was 15.2 months, median progression-free survival was 12.6 months, and median overall survival reached 30.3 months — a meaningful result in this aggressive disease setting. No unexpected toxicities emerged, but drug-related interstitial lung disease or pneumonitis occurred in 20.7% of patients, with one fatal case.
These findings suggest that durvalumab and T-DXd together offer clinically relevant benefit as first-line treatment in HR-negative, HER2-low metastatic breast cancer. The overall survival data, in particular, compare favorably to historical benchmarks for this population.
Important caveats apply. The trial was a relatively small, single-arm, open-label study without a randomized comparator, making it difficult to isolate the contribution of durvalumab beyond T-DXd alone. The lung toxicity rate warrants close clinical monitoring. Additionally, this summary is based solely on the abstract, and full methodology and subgroup analyses are not available for review.
Key Findings
- Durvalumab plus T-DXd achieved 62% objective response rate in first-line HR-negative, HER2-low metastatic breast cancer.
- Median overall survival reached 30.3 months, a clinically meaningful outcome for this aggressive subtype.
- Median duration of response was 15.2 months, indicating durable disease control in responders.
- Drug-related interstitial lung disease or pneumonitis occurred in 20.7% of patients, including one fatal case.
- The combination met no unexpected safety signals beyond the known profiles of each individual drug.
Methodology
BEGONIA is a multicenter, open-label phase 1b/2 platform trial; arm 6 enrolled 58 women receiving durvalumab 1,120 mg plus T-DXd 5.4 mg/kg IV every three weeks as first-line therapy. The trial was single-arm with no randomized comparator, and median follow-up was 20.6 months. Primary endpoints were objective response rate and safety.
Study Limitations
The trial was a small, non-randomized, single-arm study, limiting causal attribution and generalizability. The predefined response benchmark of 66.6% was not met, qualifying the efficacy interpretation. This summary is based on the abstract only, as the full paper is not open access, so detailed subgroup analyses, patient characteristics, and methodology cannot be fully assessed.
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