Dual-HER2 targeted therapy has led to a promising antitumor effect in HER2 positive cancers including gastrointestinal cancer. The present data focus on patients with HER2 positive colorectal cancer who received pyrotinib and trastuzumab after failure to standard second-line treatment.Patients diagnosed of HER2 positive refractory or metastatic colorectal cancer were enrolled to receive trastuzumab in combination with pyrotinib as third-line and beyond therapy. Trastuzumab was given as a loading dose at 8 mg/kg followed by 6mg/kg once every 3 weeks, and oral pyrotinib as 400 mg per day until progression. ORR was set as the primary endpoint. PFS and OS were set as a secondary endpoints. This trial is registered with Clinical Trial.gov, NCT04960943, and is ongoing.Between February 2020 to December 2021, 16 patients including 14 with RAS wild-type status were enrolled in this cohort. ORR was 50.0% in the overall population, and 57.1% in RAS wild-type patients. At a median follow-up of 11.2 months, median PFS and OS were 7.53 and 16.8 months, respectively. The RAS/BRAF wild-type patients had prolonged survival (PFS: 7.53 vs. 1.63 months, P = .02; OS: NR vs.4.13 months, P = .001) compared with RAS/BRAF mutant patients. The most common treatment-emergent adverse event (TEAE) reported is diarrhea. Five (31.3%) patients reported grade 3 TEAEs, and no death was reported.Trastuzumab in combination with pyrotinib demonstrated encouraging antitumor activity that translated to prolonged survival benefit in HER2 positive refractory or mCRC patients who are RAS wild-type with acceptable tolerance.
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