LAUSR

This trial was initiated to evaluate the efficacy and safety of pyrotinib in combination with trastuzumab in patients with human epidermal growth factor receptor 2 (HER2)‐positive recurrent/metastatic colorectal cancer (CRC). In this single‐arm, open‐label, multicenter, phase 2 trial patients with HER2‐positive recurrent/metastatic CRC were enrolled and received oral pyrotinib 400 mg once a day plus intravenous trastuzumab 8 mg/kg loading dose followed by 6 mg/kg once every 3 weeks. The primary endpoint was the objective response rate (ORR). Disease control rate (DCR), progression‐free survival (PFS), duration of response, and safety were assessed as secondary endpoints. From December 2019 to October 2021, a total of 20 patients were enrolled and 18 of them were evaluable for response. All patients were B‐rapidly accelerated fibrosarcoma (BRAF) wild type. Four patients achieved partial response, with an ORR of 22.2% (4/18, 95% confidence interval [CI] 6.4–47.6) and DCR of 61.1% (11/18, 95% CI 35.8–82.7), while the ORR and DCR were 33.3% (4/12, 95% CI 13.8–60.9) and 83.3% (10/12, 95% CI 51.6–97.9), respectively, in RAS wild‐type patients. At the time of cut‐off day, median follow‐up was 10.7 months (range 3.8–13.8). The median PFS was 3.4 months (95% CI 1.8–4.3) in the overall population and 4.3 months (95% CI 3.2–8.5) in the RAS wild‐type group. The most common adverse event of grade ≥3 was diarrhea (13/20, 65.0%). Pyrotinib combined with trastuzumab showed promising antitumor activity and a manageable safety profile in patients with RAS/BRAF wild‐type HER2‐positive advanced CRC.