Immune checkpoint inhibitors combined with chemotherapy/bevacizumab therapy for patients with advanced lung cancer and heavily treated with EGFR mutation: a retrospective analysis

BACKGROUND: EGFR-mutated lung cancer poorly responded to anti-programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) monotherapy. Whether patients with EGFR-mutated lung cancer can benefit from anti-PD-1/PD-L1 therapy combined with other drugs remains controversial. We retrospectively evaluated the safety and efficacy of the PD-1 inhibitor combined with other drugs (chemotherapy and/or bevacizumab) in patients with EGFR-mutated lung cancer, who have progressed on EGFR–TKI treatment to determine the activity of the anti-PD-1/PD-L1 therapy combined with chemotherapy or/and bevacizumab therapy in heavily treated patients with EGFR-mutated lung cancer. METHODS: We identified 56 patients with EGFR-mutated lung cancer treated with PD-1/PD-L1 inhibitors alone or combined with the chemotherapy/bevacizumab therapy. The objective response rates were assessed using RECIST v1.1. Adverse events (AEs) were graded in accordance with the National Cancer Institute Common Terminology Criteria for Adverse Events v4.0. The study was conducted in accordance with the Declaration of Helsinki (as revised in 2013). The study was approved by the Academic Ethics Committee of Jiangsu Cancer Hospital. (NO. 2019 160), and individual consent for this retrospective analysis was waived. RESULTS: Objective responses were observed in 6 of 56 (10.7%) patients, and the disease control rate was 53.6% (30/56). The median progression-free survival (PFS) was 3.33 months with 95% CI of 1.58–5.08 months. No patient achieved a complete response. All six patients that achieved PR were treated with the PD-1 inhibitor combined with chemotherapy or bevacizumab therapy. Three of the six patients who achieved PR were treated with radiotherapy combined with PD-1 inhibitor-based therapy. Patients treated with the PD-1 inhibitor-based therapy as second-line therapy showed relatively longer PFS and higher objective response rates than those treated with PD-1 inhibitor-based therapy as third- or late-line therapy (PFS: 5.50 vs. 3.27 months, P=0.301; objective response rates: 25.0% vs. 6.82%, P=0.071). No additional AE profile was observed. CONCLUSIONS: The PD-1 inhibitor combined with the chemotherapy/bevacizumab therapy showed acceptable toxicity profile and moderate efficacy on heavily treated advanced EGFR-mutated lung cancer after the exhaustion of target therapy.