Neoadjuvant pyrotinib and trastuzumab in HER2-positive breast cancer with no early response (NeoPaTHer): Primary analysis of a prospective, multicenter, response-adapted study.

603 Background: The contribution of biological characteristics and treatment patterns to the survival difference between male and female breast cancer patients is understudied, which is controversial but fundamental in determining strategies for cancer treatment and survivorship care. To evaluate the efficacy and safety of additional pyrotinib in patients with HER2-positive breast cancer who had no early response to neoadjuvant trastuzumab in combination with chemotherapy. Methods: A prospective, multicenter, response-adapted study including patients diagnosed with HER2-positive breast cancer from 2020 to 2022 were conducted. A total of 129 female patients from 5 hospitals participated in this neoadjuvant setting study. The primary endpoint was pathological complete response ( pCR), defined as the absence of invasive cancer in both the breast and axilla as determined by a local pathologist after surgery (ypT0ypN0). Results: Among 129 enrolled participants, 62 (48.1%) were identified as MRI-responders (Cohort A), 26 non-responders received 4 more cycles of TCbH (Cohort B), while 41 received additional pyrotinib (Cohort C). The pCR rates were 30.6% (95%CI: 20.6%-43.0%) in Cohort A, 15.4% (95%CI: 6.2%-33.5%) in Cohort B and 29.3% (95%CI: 17.6%-44.5%) in Cohort C. Similar difference patterns of breast pCR rates across 3 cohorts were observed. Multivariable logistic regression analyses showed that, in comparison to those in Cohort A, patients in Cohort C had comparable probability of pCR (OR=1.03, 95%CI: 0.40 to 2.67). The most common adverse events among patients who received pyrotinib were diarrhoea, anaemia, and erythropenia, and no cardiovascular event was observed. Participants with low TMB and no RTK-RAS mutation had a quite low pCR rate of 4%. Conclusions: The addition of pyrotinib to trastuzumab increases the pCR rates among patients who had no early response to neoadjuvant trastuzumab. Further studies are warranted to identify biomarkers predicting those who may benefit from pyrotinib in addition to trastuzumab. Clinical trial information: NCT03847818 .