Acquired resistance is unavoidable with the approval of third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) for first-line therapy of advanced non small cell lung cancer (NSCLC). Some studies have found that combining antiangiogenesis medicines with EGFR-TKI may benefit clinical outcomes in EGFR-mutant NSCLC. However, it is unclear whether EGFR-TKI paired with antiangiogenesis therapy could further improve survival for patients with gradual progression. Thus, we comprised the clinical effectiveness and safety of continuous EGFR-TKI in combination with anlotinib and EGFR-TKI alone in patients who had gradual progression on third-generation EGFR-TKI treatment. The comparison of progression-free survival (PFS) and overall survival(OS) between two groups used the Kaplan-Meier method. Our study comprised 121 eligible patients in total. The objective response rates were 25.0% and 0%, and the disease response rate was 91.7% and 86.9% in the combination group and EGFR-TKIs monotherapy group. The median PFS of combined anlotinib and EGFR-TKI treatment was 6.7 months and the median PFS was 3.6 months in the EGFR-TKI monotherapy group (P < 0.001). There were no significant differences between the two groups in OS. The common adverse reactions were diarrhea (21.7%), hypertension (21.6%) and proteinuria (20.0%) in the combination group. Seven patients experienced a grade 3 or higher adverse event, no patients discounted the treatment or died due to the toxicity. Our study indicated that, when combined with anlotinib following gradual progression on EGFR-TKIs, it was more efficacious for EGFR-mutant NSCLC patients than EGFR-TKI monotherapy. And the toxicity was clinically manageable.

中文翻译：

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在第三代 EGFR-TKIs 中渐进添加安罗替尼治疗 EGFR 突变晚期非小细胞肺癌的疗效和安全性。

随着第三代表皮生长因子受体（EGFR）酪氨酸激酶抑制剂（TKI）被批准用于晚期非小细胞肺癌（NSCLC）的一线治疗，获得性耐药是不可避免的。一些研究发现，抗血管生成药物与 EGFR-TKI 联合治疗可能有益于 EGFR 突变 NSCLC 的临床结果。然而，尚不清楚 EGFR-TKI 联合抗血管生成治疗是否可以进一步提高逐渐进展患者的生存率。因此，我们纳入了连续 EGFR-TKI 联合安罗替尼和单独 EGFR-TKI 对于第三代 EGFR-TKI 治疗逐渐进展的患者的临床有效性和安全性。两组间无进展生存期（PFS）和总生存期（OS）的比较采用Kaplan-Meier法。我们的研究总共包括 121 名符合条件的患者。联合组和EGFR-TKIs单药治疗组的客观缓解率为25.0%和0%，疾病缓解率为91.7%和86.9%。安罗替尼联合 EGFR-TKI 联合治疗的中位 PFS 为 6.7 个月，EGFR-TKI 单药治疗组的中位 PFS 为 3.6 个月（P < 0.001）。两组之间的 OS 没有显着差异。联合组常见的不良反应为腹泻（21.7%）、高血压（21.6%）和蛋白尿（20.0%）。7 名患者出现 3 级或以上不良事件，没有患者放弃治疗或因毒性而死亡。我们的研究表明，在 EGFR-TKI 逐渐进展后与安罗替尼联合治疗 EGFR 突变 NSCLC 患者比 EGFR-TKI 单药治疗更有效。而且毒性在临床上是可控的。