In this multicenter, single-arm, phase II trial, stage IIIB-IV NSCLC patients harboring HER2 mutations, as determined using next-generation sequencing, were enrolled and treated with pyrotinib at a dose of 400 mg/day....The 12-month PFS and OS rates were 28.4% and 38.6%, respectively. The mPFS and mOS were 5.6 months (95% CI, 2.8–8.4 months) and 10.5 months (95% CI, 8.7–12.3 months), respectively. Overall, 15 patients had a PR, for an ORR of 19.2% (15/78; 95% CI, 11.2–30.0%), including 11 patients with HER2 mutations in exon 20, three in exon 19, and one in exon 17 (Table 2, Fig. 3).