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.

Competing Interest Statement

The authors have declared no competing interest.

Clinical Trial

NCT05934461

Funding Statement

Yes

Author Declarations

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Yes

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

The present study was conducted according to the Declaration of Helsinki and received approval from the Ethics Committee of The People's Hospital of Laibin (approval no.2022-54.Laibin,China), The First People's Hospital of Yulin (approval no. 2022-95. Yulin,China), and Guangxi Medical University Kailuan Langdong Hospital (approval no.2022-73.Nanning,China).

I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.

Yes

I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).

Yes

I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.

Yes

Data Availability

All relevant data are within the manuscript and its Supporting Information files.

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