Integrative Multiomics Profiling Reveals Immune Determinants of Response to Disitamab Vedotin Plus Penpulimab in HER2-Low Breast Cancer
In brief
The drug combination produced complete tumor clearance in 4 of 20 patients
In this small, single-arm study of stage II-III HER2-low breast cancer, 20% of patients had no cancer detected in their surgical specimen after treatment, and 45% had an objective response. Severe adverse events occurred in one in four, with no treatment-related deaths. The results suggest antitumor activity, but larger randomized trials are needed to establish benefit.
- Journal
- MedComm (Q1)
- Published
- 4 October 2026
- Study design
- Randomized controlled trial
- Evidence level
- Level 1, High (CEBM 1b)
- Authors
- Xiaoxiao Liu, Yuting Song, Lei Liu, Aaron Qi Zhang, Xin Xie, Bing Wei, et al.
- PMID
- 42830862
- DOI
- 10.1002/mco2.70988
Why clinicians should know about it
- Picked for Oncology and Radiation Oncology (paper of the day, 8 October 2026): Neoadjuvant ADC + PD‑1, pCR data
Abstract
This prospective single-arm study evaluated neoadjuvant disitamab vedotin plus penpulimab in Stage II-III HER2-low breast cancer (immunohistochemistry 1+ or 2+, fluorescence in situ hybridization-negative), a population lacking targeted neoadjuvant options. Twenty patients received the combination every 3 weeks for six cycles before surgery. In the intention-to-treat population, the pathologic complete response (pCR) was 20.0% (four out of 20; 95% CI, 5.7-43.7%), and the objective response rate (ORR) was 45.0% (nine out of 20; 95% CI, 23.1-68.5%). Among 16 patients who completed protocol-defined treatment and surgery, pCR was 25.0% (four out of 16; 95% CI, 7.3-52.4%), ORR was 56.3% (nine out of 16; 95% CI, 29.9-80.2%), and 31.3% achieved residual cancer burden Class 0-1. Grade ≥3 adverse events occurred in 25.0%; no treatment-related deaths occurred. pCR-associated tumors had a pretreatment immune-active microenvironment enriched in inflammatory proteins, transcripts, and tumor-infiltrating lymphocytes, whereas nonresponders displayed a higher M2/M1 macrophage ratio. An exploratory baseline score combining CCL19 and the M2/M1 ratio showed pCR/non-pCR separation (AUC = 0.8889) but attenuated on internal validation (LOOCV AUC = 0.6667, optimism-corrected bootstrap AUC = 0.8375). This combination showed preliminary antitumor activity with manageable safety; however, given the small sample size and wide confidence intervals, these findings preclude definitive conclusions about efficacy and warrant validation in larger randomized controlled trials.
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.