Timing in Combination with Radiotherapy and Patterns of Disease Progression in Non-small Cell Lung Cancer Treated with EGFR-TKI

Objectives: Tyrosine kinase inhibitor (TKI) has been the standard of care for advanced non-small cell lung cancers (NSCLC) harboring epidermal growth factor receptor (EGFR) mutation, but these tumors invariably develop drug resistance. As progression most frequently advances in sites of original disease, our study sought to explore the time to response for NSCLC to TKI therapy and the patterns of disease progression, to provide evidence for timing and candidates for local therapy intervention.

Materials And Methods: A cohort of 105 EGFR-mutated IIIB or IV NSCLC patients treated with EGFR-TKI were retrospectively analyzed. The disease progression patterns were divided into 3 categories: progression in sites of original disease, progression in new distant sites, and combined progression.

Results: Before cut-off date, 80 patients had disease progression. Thirty-three (41.25 %) patients had progression in sites of original disease, 34 (42.5 %) patients had progression in new sites and 13 (16.25 %) patients had combined progression, respectively. The median time to response for responders was 2.00 months (95 %CI 1.28-2.92 months), and the median time to maximal tumor shrinkage for SD patients was 2.00 months (95 %CI 1.42-2.58 months). Multivariate logistic regression model showed that the 21 exon mutation is related to the incidence of original site failure.

Conclusion: Over 1/3 of the patients progress at the original sites, which indicated that this subset of patients may benefit from local therapy. Moreover, as the results indicate that considerable shrinkage for TKI therapy occurs in first two months after TKI initiation, local therapy can be adopted after this timepoint, before disease progression. We also propose EGFR gene mutation type as potential inclusion criteria to identify candidates for combined local therapy.