Is a delay in ALK inhibitor initiation associated with poorer survival? A retrospective analysis based on real-world data.

Abstract

e18240 Background: The time between a patient’s positive biomarker test result and initiation of targeted therapy may vary due to a number of factors, including the use of chemotherapy prior to or after the biomarker test result. The objective of this study was two-fold: first, to investigate the impact of delayed ALK inhibitor (ALKi) therapy on overall survival (OS) and second, to examine the association between the use of chemotherapy prior to or after biomarker testing and OS. Methods: The Flatiron Health EHR-derived database was used to identify patients with ALK-positive (ALK+) advanced NSCLC diagnosed between 1/1/2011 - 9/30/2018. The median time from ALK+ test result to ALKi start was used to separate patients into early versus delayed treatment cohorts. To account for potential immortal time bias, times from ALK+ test result to ALKi start from the delayed cohort were sampled with replacement and used to create modified index dates among the early cohort. Cox proportional hazards models adjusting for baseline characteristics (i.e. ECOG) were used to assess the association between delayed ALKi start and OS and the use of chemotherapy with OS. Results: 422 patients with ALK+ aNSCLC were included in this analysis with a median time from test result to ALKi start of 3 weeks. 88 patients (20.9%) received chemotherapy prior to starting their ALKi. Delayed ALKi use was associated with a 2.3 fold increase in risk of mortality (HR [95% CI]: 2.30 [1.28, 4.15], p < 0.01). There was no difference in survival observed between those who had received chemotherapy prior to initiating their ALKi and those who did not receive chemotherapy (HR [95% CI]: 0.99 [0.62, 1.58]). Among those who initiated chemotherapy prior to their ALK+ test result, the continued use of chemotherapy prior to initiating an ALKi did not result in differences in OS compared to those who switched to an ALKi without continuing chemotherapy (HR [95% CI]: 1.03 [0.44, 2.41]). Conclusions: Delayed initiation of ALKi may result in poor outcomes in patients with ALK+ NSCLC. Receipt of chemotherapy prior to ALKi or the duration of chemotherapy did not impact survival. Future strategies to improve the time to therapy initiation may be useful in improving patient outcomes.