Efficacy and safety of pyrotinib combined with trastuzumab emtansine (T-DM1) for patients with advanced HER2-positive breast cancer (BC): A single-arm phase II trial.

e13005 Background: The Chinese Society of Clinical Oncology Guidelines recommended the pyrotinib plus capecitabine regimen as the standard of care for patients with HER2+ advanced BC who relapsed after trastuzumab therapy (class I recommendation, level of evidence: A), based on the PHENIX and PHOEBE studies. However, there is no established standard of care for patients with HER2-positive advanced BC who failed tyrosine kinase inhibitor (TKI) therapy. Given that the safety profile of TKIs such as neratinib and tucatinib has been investigated in several clinical trials when combined with T-DM1, our aim is to explore the efficacy and safety of pyrotinib plus T-DM1 in patients with HER2-positive advanced BC who progressed after TKI treatment. Methods: In this single-arm, multicenter, exploratory phase II clinical trial, patients aged 18 to 79 years with HER2-positive advanced BC who progressed after TKI treatment are enrolled. Pyrotinib (320 mg, orally, once daily) combined with T-DM1 (3.6mg, intravenously, every 3 weeks) is administered until unacceptable toxicities or disease progression. The co-primary endpoints are investigator-determined objective response rate (ORR) and safety. The secondary endpoints include disease control rate (DCR), PFS, and overall-survival. We assess the ORR and safety using the Bayesian optimal phase 2 design. The null hypotheses are ORR 70%. When the total number of patients reaches the maximum sample size of 50, the null hypothesis will be rejected if 13 or more response are observed, and 35 or less patients experience grade 3 and above AEs. The interim analysis will be conducted when 10, 20 and 35 patients are evaluable to make the go/no-go decision. In the first-stage, the study will stop if fewer than 1 patient responds and more than 8 patients experience grade 3 and above AEs. Results: From March 2023 to December 2023, 10 patients were enrolled in the present study. The median age was 53.5 years (range: 38-58). The median number of metastatic sites was 3 (range: 1-5). Eight patients had visceral metastasis, among them 4 had multiple organic metastasis. Eight patients received pyrotinib, 1 received lapatinib, and 1 received neratinib. The confirmed best ORR was 30% (3/10), and the incidence of grade 3 and higher adverse events was 20% (2/10), exceeding the pre-specified threshold. Until January 24, 2024, the median follow-up time was 10.7 months (95% CI: 8.63-NA). Four patients had progressive disease. The median PFS was 7.77 (95%CI 3.30-NA), and the 6-month PFS rate was 57.14%. Grade 3 and above treatment-related AEs include platelet count decreased (1/10) and paronychia (1/10). No grade 4 or 5 AEs and death were reported. Conclusions: The first-stage interim analysis revealed acceptable efficacy and toxicity. The study will proceed to the second stage. Clinical trial information: NCT05560308 .