The EGFR-TKIs treatment challenge in NSCLC: Changes in survival after COVID-19 infection.

e20538 Background: COVID-19 has emerged as a major public health emergency with long-term impacts, especially on cancer patients who are more susceptible to SARS-CoV-2 infection and have worse health outcomes. However, no studies have explored its impact on EGFR-TKI treatment in lung cancer. This study aims to fill this gap and provide clinical guidance. Methods: This study was a retrospective multi-center real-world analysis of EGFR-mutated lung cancer patients treated with EGFR-TKIs at four Chinese medical institutions, spanning pre-COVID-19 period (January 2019 through November 2022) and post-COVID-19 period (January through June 2023). Kaplan-Meier analysis was used to assess PFS, and Cox regression for survival analysis of prognostic factors. A 1:1 propensity score matching (PSM) with bootstrapping and nearest-neighbor matching (caliper 0.2) was performed to reduce biases. All statistical tests were two-tailed, with significance set at P < 0.05. Results: A total of 598 lung cancer patients with mutated EGFR were included in this study. Considering the retrospective nature of this multicenter study, we performed PSM in patient’s cohort. A well-matched cohort of 478 patients (239 pre-COVID19 vs 239 post-COVID19) was generated with balanced clinical characteristics. The median follow-up time was 15.07 (0.53-65.20) months. The results showed that patients in the pre-COVID-19 group had better progression-free survival (PFS) regardless of whether they were treated with first-generation or second- and third-generation EGFR-TKIs. The cumulative incidences of tumor progression in pre-COVID-19 group and post-COVID group were estimated to be 24.69% vs 48.54% at 12 months (P<0.001) and 41.84% vs 60.25% at 18 months (P<0.001). The median PFS were 18.10 and 11.73 months respectively. On univariable Cox proportional hazard analyses, it was observed that COVID-19 suffering was linked to a worse PFS (HR, 1.676, 95% CI, 1.261-2.175; P<0.001). Besides that, smoking history, the 3rd, and 1st generation of EGFR-TKIs, gender, liver metastasis, combined therapy were also found to be associated with PFS. And COVID-19 suffering, smoking history, 3rd generations of EGFR-TKIs, liver metastases and concurrent systemic treatment were significant factors associated with PFS on the final multivariable analysis. The subgroup analysis results showed that the 3rd generation of EGFR-TKIs showed a better survival outcome than the other generations. And patients with concurrent systemic treatment such as bevacizumab or chemotherapy seems to have better survival. Conclusions: This study pointed out that COVID-19 infection could reduce the efficacy of EGFR-TKIs in EGFR-mutated NSCLC patients at the first time. Thus, in the clinical management of these patients, a more robust combined treatment approach may be needed to enhance the efficacy of targeted therapy, while also requiring more frequent follow-up examinations.