Analysis of Poor Prognostic Factors and Treatment Strategies in Platinum-Based Systemic Therapy After EGFR-TKI Failure in Patients With Advanced Nonsmall Cell Lung Cancer Harboring EGFR Mutations.

Background: The aim of this study was to identify poor prognostic factors and explore optimal second-line treatment strategies for patients with epidermal growth factor receptor (EGFR)-mutant nonsmall cell lung cancer (NSCLC) who developed resistance to EGFR tyrosine kinase inhibitors (TKIs).

Patients And Methods: We retrospectively evaluated patients with advanced or recurrent EGFR-mutant NSCLC who received platinum-based systemic therapy after EGFR-TKI failure from January 2017 to July 2022 at 20 institutions. Logistic regression analysis was used to identify factors associated with 1-year mortality after the start of systemic therapy.

Results: We included 393 patients in the final analysis (101 received atezolizumab, bevacizumab, carboplatin, and paclitaxel [ABCP], 292 received chemotherapy); 143 (36.3%) had an overall survival (OS) <1 year. Compared to the group with OS ≥1 year, the group with OS <1 year had significantly higher rates of performance status (PS) 2-4 and brain, liver, and bone metastases. Multivariable analysis revealed that PS ≥2, bone metastasis, and failure to respond to pretreatment EGFR-TKI were associated with poor OS. ABCP had numerical, but not statistically significant, OS improvement versus chemotherapy in patients with at least 1 poor prognostic factor (P = .079). Among patients with bone metastases (48.3%, n = 190), those treated with ABCP had a significantly longer median OS than those treated with chemotherapy (P = .032).

Conclusion: EGFR-mutant NSCLC with PS ≥2 or bone metastases was associated with a poor prognosis after EGFR-TKI failure. Patients with poor prognostic factors, especially bone metastases, may benefit more from ABCP than from chemotherapy.