Neoadjuvant concurrent or sequential anthracycline-containing chemotherapy and HER2-targeted agents for HER2-positive breast cancer: a randomized phase 2 study (METIS).

@article{zheng2026neoadjuvant,
  title = {{Neoadjuvant concurrent or sequential anthracycline-containing chemotherapy and HER2-targeted agents for HER2-positive breast cancer: a randomized phase 2 study (METIS).}},
  author = {Qiufan Zheng and Shusen Wang and Zhiyong Wu and Muyi Zhong and Fei Xu and Shihui Ma and Yuanqi Zhang and Lehong Zhang and Yanxia Shi and Ying Wang and Heng Huang and Xiaopeng Ma and Xiangdong Xu and Haiyan Li and Jibin Li and Xiwen Bi and Jiajia Huang and Kuikui Jiang and Xin An and Ruoxi Hong and Meiting Chen and Cong Xue and Yongyi Zhong and Zhongyu Yuan and Wen Xia},
  journal = {Signal transduction and targeted therapy},
  year = {2026},
  month = nov,
  doi = {10.1038/s41392-026-02834-x},
  url = {https://europepmc.org/article/MED/42967914},
  note = {CC BY-NC-ND},
}

TY  - JOUR
TI  - Neoadjuvant concurrent or sequential anthracycline-containing chemotherapy and HER2-targeted agents for HER2-positive breast cancer: a randomized phase 2 study (METIS).
AU  - Qiufan Zheng
AU  - Shusen Wang
AU  - Zhiyong Wu
AU  - Muyi Zhong
AU  - Fei Xu
AU  - Shihui Ma
AU  - Yuanqi Zhang
AU  - Lehong Zhang
AU  - Yanxia Shi
AU  - Ying Wang
AU  - Heng Huang
AU  - Xiaopeng Ma
AU  - Xiangdong Xu
AU  - Haiyan Li
AU  - Jibin Li
AU  - Xiwen Bi
AU  - Jiajia Huang
AU  - Kuikui Jiang
AU  - Xin An
AU  - Ruoxi Hong
AU  - Meiting Chen
AU  - Cong Xue
AU  - Yongyi Zhong
AU  - Zhongyu Yuan
AU  - Wen Xia
PY  - 2026
DA  - 2026/11/02
JO  - Signal transduction and targeted therapy
DO  - 10.1038/s41392-026-02834-x
UR  - https://europepmc.org/article/MED/42967914
AB  - The integration of anthracyclines with HER2-targeted agents in neoadjuvant therapy for HER2-positive breast cancer has been limited by cardiotoxicity concerns. This randomized phase II METIS trial (NCT04172259) assessed whether concurrent pegylated liposomal doxorubicin (PLD)-containing chemotherapy plus dual HER2 blockade (trastuzumab/pertuzumab) could improve efficacy without increasing cardiac risk. A total of 156 patients with stage II-III HER2-positive breast cancer were randomized to a PLD-based concurrent regimen or an epirubicin and cyclophosphamide (EC)-based sequential regimen. The PLD-based concurrent group achieved a higher pathological complete response (pCR) rate (67.5% vs. 48.7%; difference, 18.8%; 95% confidence interval [CI], 3.6-34.0; P = 0.033) compared with the EC-based sequential group, with greater benefit in hormone receptor-positive disease (58.7% vs. 36.7%) and stage II tumors (82.1% vs. 48.0%). After a median follow-up of 37.5 months, fewer event-free survival (EFS) events occurred in the PLD-based concurrent group (3 vs. 8), yielding a hazard ratio (HR) of 0.35 (95% CI, 0.09-1.32; P = 0.105). The estimated 3-year EFS rates were 96.0% (95% CI, 88.1-98.7) versus 90.7% (95% CI, 81.5-95.6). Achieving pCR was significantly associated with improved EFS (HR = 0.15; 95% CI, 0.03-0.71; P = 0.006). Cardiac safety was comparable, with no symptomatic cardiac dysfunction and only one grade ≥3 cardiotoxicity in the EC-based sequential group. These findings support PLD-based concurrent therapy with trastuzumab and pertuzumab as an effective and safe neoadjuvant option for high-risk HER2-positive breast cancer, warranting further evaluation in phase III trials.
SN  - 2095-9907
SN  - 2059-3635
ER  -