Neoadjuvant trastuzumab rezetecan in HER2-positive breast cancer

The first study reporting the efficacy and safety of the third generation HER2-directed antibody-drug conjugate trastuzumab rezetecan in patients with HER2-positive breast cancer has been recently published on Annals of Oncology.

This phase 2 trial enrolled 265 patients with stage II-III HER2-positive breast cancer, randomized to receive neoadjuvant therapy for 24 weeks with trastuzumab rezetecan (or SHR-A1811) as monotherapy or in combination with pyrotinib or nab-paclitaxel combined with carboplatin, trastuzumab, and pertuzumab. The pathological complete response was 63.2%, 62.5% and 64.4% respectively, with no statistical significance between groups. Grade ≥3 treatment-related adverse events occurred in 44.8% of patients with mono-SHR-A1811, 71.6% with SHR-A1811 plus pyrotinib, and 38.8% with nab-paclitaxel combined with carboplatin, trastuzumab, and pertuzumab. «Although the addition of pyrotinib to SHR-A1811 did not improve the overall pathological complete response rate, we observed that the combination treatment performed better in some subgroups (N3 and stage III), which may warrant further exploration», authors point out. «Neoadjuvant SHR-A1811 showed robust activity and a favorable safety profile as monotherapy, presenting a potential alternative to the conventional four-drug combination regimen, and future trials may explore whether SHR-A1811 can serve as a backbone and be combined with other target drugs in the neoadjuvant setting».