2189 - Efficacy of Radiotherapy Combined with EGFR-TKI in the Treatment of EGFR/TP53 Co-Mutated NSCLC

S. Zeng¹, L. L. WANG¹, D. Tao¹, W. Zhou¹, and Y. Wu²; ¹Department of Radiation Oncology, Chongqing University Cancer Hospital, Chongqing, China, ²College of Medicine, Chongqing University, Chongqing, China

Purpose/Objective(s): The efficacy of EGFR-TKIs in the treatment of EGFR/TP53 co-mutated NSCLC is suboptimal, and the efficacy of radiotherapy in combination with EGFR-TKI in this subgroup is unclear. The purpose of this study was to investigate the efficacy of radiotherapy combined with EGFR-TKI in patients with EGFR/TP53 co-mutated NSCLC. Materials/

Methods: In this study, patients with advanced NSCLC with EGFR/TP53 co-mutations who were admitted to the Cancer Hospital from February 2019 to December 2022 were included, with PFS and OS as the main endpoints, and the differences between PFS and OS between radiotherapy combined with EGFR-TKI and EGFR-TKI alone were analyzed by log-rank test. Differences between the two groups in the site of post-treatment progression were analyzed using the chi-square test.
Results: A total of 256 patients were enrolled in this study, including 61 (23.8%) in the radiotherapy combined with TKI group and 195 (76.2%) in the TKI alone group. The median follow-up was 15.3 months. PFS was significantly better in the radiotherapy plus TKI group than in the TKI alone group (17.9 months vs. 15.0 months, P = 0.037). The median OS of PFS in the radiotherapy plus TKI group and the TKI alone group was 45.8 months and 46.3 months, respectively, and the difference in OS between the two groups was not statistically significant (P = 0.9). Subgroup analysis of EGFR mutation typing found that in the population with the EGFR L858R mutation, PFS was significantly longer in the radiotherapy plus TKI group compared with TKI alone (20 versus 13 months, P = 0.02). In the subgroup with metastases to different organs, it was found that the median PFS of patients with liver metastases was significantly worse than that of EGFR-TKI monotherapy (10.9 months vs. 42.6 months, P = 0.004), and there was no statistically significant difference between the groups for other metastases (brain, bone, adrenal glands). There was no statistically significant difference in the pattern of progression (primary site, lymph nodes, distant metastases, liver, brain, bone, adrenal progression) between combination therapy and monotherapy.
Conclusion: Radiotherapy combined with EGFR-TKI significantly prolonged PFS in patients with advanced NSCLC with EGFR/TP53 co-mutations, and the PFS benefit was more significant in patients with EGFR L858R mutations. This study suggests that radiotherapy combined with EGFR-TKI is a potential treatment to improve the survival of EGFR/TP53 co-mutated advanced NSCLC, which needs to be further validated by prospective, multicenter, randomized double-blind clinical studies.