Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKI) acquired resistance was an inevitably events in NSCLC treatment. Intending to overcome the acquired resistance of EGFR-TKI. A clinical trial was, we enrolled 12 patients who were slowly progressing on first-generation EGFR-TKI, and added apatinib when the patients got slow progression. Seven patients were included in the efficacy analysis. The median PFS2 of apatinib combined with EGFR-TKI was 8.2 months (95% CI, 7.3 m-NA), and the total PFS reached 20.9 months (95% CI, 17.3 m-NA) when plus PFS1. All the adverse events were manageable. The median PFS was significantly longer for circulating tumor DNA (ctDNA)-cleared patients (8.4 months; 95% CI, 8.2-NA) than for those ctDNA not cleared (7.1 months; 95% CI, 6.9-NA) (p = 0.0082). The addition of apatinib did improve the duration of first-generation EGFR-TKI use, and the duration was better than the first-line use of third-generation EGFR-TKI. The addition of apatinib when the patients got slow progression after initial EGFR-TKI therapy may be a good treatment option and the side effects are controllable. It is possible to monitor treatment efficacy using ctDNA.