Efficacy and safety of pyrotinib in patients with previously treated HER2-positive non-breast solid tumors: a phase 2, open-label basket trial

Background Amplification/overexpression of the human epidermal growth factor receptor 2 (HER2) gene drives cell proliferation, differentiation, and migration of breast cancer. However, HER2-targeted therapies are not standard treatment for HER2-positive non-breast solid tumors currently. This phase II open-label basket trial evaluated pyrotinib’s efficacy and safety in patients with non-breast solid tumors. Methods Patients with previously treated HER2-positive advanced non-breast solid tumors were enrolled at Zhongshan Hospital, Fudan University. All participants received pyrotinib in 21-day cycles. Primary endpoint was objective response rate (ORR) at 6 weeks, assessed per RECIST version 1.1. Circulating tumor DNA (ctDNA) analysis was conducted to identify biomarkers of efficiacy. Results Fifty-three patients were enrolled and 51 evaluable for efficiacy analysis. The median follow-up was 32.2 months. ORR was 18.9% (95% CI: 10.2–31.7%) and disease control rate was 73.6% (95% CI: 60.1–84.2%). Median progression-free survival (mPFS) was 5.1 (95% CI: 4.2-8.1) months and median overall survival (mOS) was 17.2 (95% CI: 16.2-33.2) months. Patients with colorectal cancer had the highest ORR and the longest mOS (33.2 months, 95% CI: 14.9-51.5). Among patients with HER2 overexpression, those with immunohistochemistry 3+ had longer mPFS and mOS. Sixteen patients required dose reductions due to grade 3 adverse events (AEs); no ≥grade 4 AEs occurred. Analysis of ctDNA revealed that patients with progression disease (PD) had higher mutation frequency, more diverse mutational profiles, and higher copy number burden. Conclusion Pyrotinib demonstrated a favorable safety profile and modest efficacy in patients with previously treated HER2-positive advanced non-breast solid tumors.