Objective  To evaluate the clinical efficacy of chemotherapy, chemotherapy combined with anti-angiogenesis therapy, and immunotherapy in advanced EGFR-mutant non-small cell lung cancer (NSCLC) after tyrosine kinase inhibitor (TKI) resistance in clinical practice and to explore the optimal immunotherapy combination and clinicopathological characteristics of the dominant population.

  Methods  Data were collected from 229 patients with advanced EGFR-mutated NSCLC who developed resistance to EGFR-TKI treatment at the Cancer Hospital of Guangdong Provincial People's Hospital from January 2014 to October 2022. One hundred and twenty-two cases of the enrolled patients were assigned into non-ICI treatment group (chemotherapy and chemotherapy combined with anti-angiogenesis therapy) and 107 cases in the ICI treatment group (including immunotherapy). The association between clinical characteristics and treatment responses were retrospectively analyzed.

  Results  The median progression-free survival (PFS) of the non-ICI group (n=122) and the ICI group (n=107) were 5.2 months and 5.2 months, respectively (P=0.129). The median overall survival (OS) was 18.2 months and 14.1 months, respectively (P=0.026). Additional analysis of 107 patients treated with immunotherapy showed that the median PFS of chemotherapy combined with immunotherapy, chemotherapy combined with anti-vascular plus immunotherapy, and immune monotherapy or anti-vascular therapy combined with immunotherapy were 5.6 months, 6.7 months, and 2.3 months, respectively (P=0.074). The median OS was 15.5 months, 18.6 months, and 8 months, respectively (P=0.165). The median PFS and OS of patients with PD-L1 expression ≥50% were significantly longer than those with PD-L1 expression <50% (median PFS: 5.6 months vs. 5.0 months, P=0.040; median OS: 19.2 months vs. 12.6 months, P=0.046).

  Conclusions  The four-drug combination immunotherapy provided a better survival benefit trend in patients with advanced EGFR-mutant NSCLC after TKI resistance. Furthermore, PD-L1 expression may be used as a biomarker for predicting the benefit of immunotherapy in this population.