...1) Aged 18 to 70 years; 2) Histologically or cytologically confirmed non-small cell lung cancer with stage IV disease; 3) HER2 exon 20 insertion mutations, primary HER2 missense mutations or primary HER2 amplification (HER2 copy number detected by NGS testing >= 3.62 or HER2 FISH+) confirmed by tumor tissue or plasma, pleural effusion, cerebrospinal fluid or other specimens; 4) Pretreated with first-line chemotherapy or ErbB-TKI targeted therapy and had experienced disease progression; 5) At least one radiographically measurable lesion exists; 6) Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1; 7) Life expectancy of more than 12 week; 8) Left ventricular ejection fraction (LVEF) >= 50 percent (%) by echocardiogram (ECHO); 9) Adequate hepatic, renal, and hematologic functions are required including following parameters; a. ANC>= 1.5 x 10^9/L (1,500/mm3) b. Platelet count: >= 100 x 10^9/L (100,000/mm3) c. Hemoglobin >= 80 g/L (8 g/dL) d. SCr<= 1.5 x upper limit of normal (ULN) or creatine clearance rate >= 60 mL/min e. Total bilirubin <= 1.5 x ULN f. ALT and AST <= 2 x ULN or ALT and AST <= 5 x ULN for patients with liver metastasis g. INR <= 1.5 x UNL, PT and APTT <= 1.5 x UNL; h. Urine protein < 2+and if urine protein >= 2+, 24-hour urine protein quantitation shows that protein must be <= 1g; 10) Provide written, informed consent to participate in the study and follow the study procedures....

Metastatic NSCLC patients...harboring primary HER2 amplification, exon 20 insertion or activating missense mutations who had failed to prior chemotherapies or anti-HER2 TKIs were eligible to be enrolled...the overall ORR and DCR were 45.5% (15/33) and 93.9% (31/33), respectively. The median PFS was 6.8 (95%CI: 5.4-8.2) months. The median DoR and OS were 5.3 (95%CI: 0-11.8) and 12.9 (95%CI: 8.6-17.2) months, respectively....Pyrotinib combined with apatinib showed potent anti-tumor activity and acceptable safety profile in metastatic NSCLC with HER2 amplification or activating mutations.