Association Between
EGFR
‐
TKI
–Associated Skin Rash and Recorded Mortality in Non‐Small Cell Lung Cancer: A Real‐World Analysis Accounting for Immo
Yasutaka Ihara, Yukihiro Nakamura, Shoichiro Yamamoto ABSTRACT
Purpose
Skin rash during epidermal growth factor receptor tyrosine kinase inhibitor (EGFR‐TKI) therapy has been associated with better outcomes in non‐small cell lung cancer (NSCLC), but previous studies may have overestimated this association because of immortal time bias. We evaluated the association between EGFR‐TKI–associated skin rash and mortality while accounting for rash timing.
Methods
We identified patients with NSCLC who initiated first‐line EGFR‐TKIs between August 2018 and December 2024 using a Japanese claims database. EGFR‐TKI–associated skin rash was defined using a qualifying diagnosis and rash‐related treatment recorded in the same calendar month. We performed time‐dependent propensity score sequential matching: each patient who newly developed skin rash was matched on the rash‐onset day to patients still at risk who had not yet developed skin rash; follow‐up started on the matched day. For comparison, we also performed an analysis that did not account for immortal time bias and landmark analyses.
Results
Among 11 830 eligible patients, 560 developed incident skin rash. In the time‐dependent propensity score sequential matching analysis, 560 patients with skin rash were matched to 5600 patients without skin rash, and skin rash was associated with lower recorded mortality (HR, 0.621; 95% CI, 0.404–0.953). The estimate was stronger in the analysis not accounting for immortal time bias (HR, 0.410), whereas the association was attenuated in landmark analyses.
Conclusions
EGFR‐TKI–associated skin rash was associated with lower recorded mortality, but the association was weaker after accounting for immortal time bias. Prior studies may have overestimated this association.