Prediction of survival after de-escalated neoadjuvant therapy in HER2-positive early breast cancer: a pooled analysis of three WSG trials

A total of 713 patients were analyzed; neoadjuvant chemotherapy (paclitaxel plus pertuzumab plus trastuzumab): n = 149, neoadjuvant chemotherapy-free (pertuzumab plus trastuzumab, trastuzumab-only)/antibody-drug conjugate (ADC, trastuzumab emtansine) treatment: n = 564. Patients with pathological complete response (pCR, ypT0/is ypN0) were allowed to omit further chemotherapy; chemotherapy was mandatory after non-pCR. The 5-year iDFS rates in patients with pCR were 98% (95% CI 91% to 99%) after chemotherapy and 94% (95% CI 89% to 97%) after chemotherapy-free/ADC treatment (hazard ratio 0.76, 95% CI 0.27-2.12, P = 0.609). iDFS was comparable between patients with and without adjuvant chemotherapy after pCR to chemotherapy-free/ADC treatment (hazard ratio 1.25). In multivariable analysis, node-negative status and pCR were favorably associated with iDFS in the chemotherapy-free/ADC group. This pooled analysis demonstrates that neoadjuvant de-escalation trials with further pCR-adapted treatment (de-)escalation are feasible and appear safe for HER2-positive eBC patients. Twelve-weekly neoadjuvant paclitaxel plus HER2 blockade is effective and well tolerated. Neoadjuvant chemotherapy-free/ADC treatments can be viable alternatives for stage I-II eBC. Excellent survival after pCR to neoadjuvant chemotherapy-free/ADC treatment lays the groundwork for further de-escalation strategies.