Radiotherapy combined with EGFR-TKIs for stage III EGFR-Mutated lung cancer: A retrospective cohort study

Abstract The present study aimed to evaluate the efficacy and safety of combining thoracic RT with epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors(TKIs) in managing stage III lung cancer with EGFR mutation. Cases of patients with stage III EGFR-mutant lung cancer who received thoracic RT between December 2014 and December 2022 from multiple hospitals including The People’s Hospital of Laibin, The First People’s Hospital of Yulin and Guangxi Medical University Kaiyuan Langdong Hospital, were collected. The patients were divided into two groups based on the initial treatment approach: RT + TKIs(RT+TKI) group and RT + chemotherapy (RT+CT) group. The primary measure of interest was progression-free survival (PFS), and additional measures evaluated included objective response rate (ORR), overall survival (OS), patterns of treatment failure and adverse events. Survival analysis was performed using the Kaplan-Meier method, and the log-rank test was used to compare survival rates among different subgroups. A total of 54 patients were ultimately included, with 36 in the RT+TKI group and 18 in the RT+CT group. Regarding short-term efficacy, the ORR for the RT+TKI and RT+CT groups were 86.1 and 66.7%, respectively, with no statistically significant difference (P=0.189). Regarding long-term efficacy, the median PFS for the RT+TKI and RT+CT groups was 26.0 and 11.0 months, respectively, showing a significant difference (P<0.01). The 3 and 5-year OS rates between the RT+TKI and RT+CT groups did not exhibit statistical significance (P=0.825). Subgroup analysis revealed a statistically significant difference in PFS between the combination of RT with third-generation TKIs and first-generation TKIs (P=0.046). The Del19 subgroup exhibited a prolonged median PFS compared with the L858R subgroup, although the difference was not statistically significant (P=0.854). In terms of adverse reactions, the incidence rates of grade ≥3 hematological toxicity and gastrointestinal reactions in the RT+TKI group were significantly lower than those in the RT+CT group (P<0.05). However, the incidence rate of grade ≥3 radiation-related pneumonitis was similar between the RT+TKI and RT+CT groups, with no statistically significant difference. The results suggest that combination of RT and TKIs has superior efficacy and is a safer therapeutic approach for stage III EGFR-mutated lung cancer compared with concurrent radio-chemotherapy. The present study was registered on the ClinicalTrials.gov website on 2nd June 2023, with the trial registration number NCT05934461 .