Real-world outcomes of chemo-antiangiogenesis versus chemo-immunotherapy combinations in EGFR-mutant advanced non-small cell lung cancer patients after failure of EGFR-TKI therapy

BACKGROUND: Despite the potent efficacy of epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) in the treatment of EGFR-mutant non-small cell lung cancer (NSCLC) patients, drug resistance inevitably ensues, and there remains a paucity of treatment options in clinical practice. METHODS: We identified patients with EGFR-mutant advanced NSCLC presenting to Shanghai Pulmonary Hospital and Shanghai Chest Hospital between January 2015 and December 2020 treated with chemo-antiangiogenesis or chemo-immunotherapy combinations after EGFR-TKI resistance. Patient information was collected, and the objective response rate (ORR), disease control rate (DCR), and progression-free survival (PFS) were assessed. RESULTS: A total of 144 patients who met our inclusion criteria were enrolled. Chemo-immunotherapy combinations achieved a higher objective response rate (ORR) compared with chemo-antiangiogenesis combinations (29.5% vs. 13.0%, P=0.018). The DCR was similar between the two groups (93.0% vs. 88.6%, P=0.585), as was the median PFS (7.59 vs. 6.90 months, P=0.552). In the subgroup analyses, patients who developed secondary T790M mutations after EGFR-TKI treatment were less likely to benefit from chemo-immunotherapy combinations than their T790M-negative counterparts (3.42 vs. 7.63 months, P=0.028). For patients who received chemo-antiangiogenesis combinations after TKI resistance, no significant difference was observed in the median PFS between T790M-positive and T790M-negative patients (median PFS: 5.33 vs. 7.46 months, P=0.202). Additionally, multivariate analysis showed that an elevated platelet count was independently associated with a worse PFS for both groups. CONCLUSIONS: The efficacy of chemo-immunotherapy combinations was comparable to chemo-antiangiogenesis combinations after failure of EGFR-TKI therapy. For patients harboring EGFR T790M mutations, chemo-antiangiogenesis combinations may be the preferred therapeutic option. In addition, platelet count could be a potential prognostic factor for patients after failure of EGFR-TKI therapy. Further research should be conducted on larger populations and in a prospective setting.