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RW1 THE IMPACT OF DELAYING ALK INHIBITOR THERAPY ON OUTCOMES: A PRESCRIPTION TIME MATCHING METHOD

      Objectives

      The impact of delayed treatment has important implications in many disease areas. However, methods for controlling for immortal-time bias (ITB) in studies where all patients receive treatment are not well-characterized. This study examines a prescription-time distribution matching (PTM) approach to controlling for ITB to compare early vs. delayed ALK-inhibitor therapy (ALKi) among advanced non-small cell lung cancer (aNSCLC) patients.

      Methods

      The Flatiron Health EHR-derived database was used to create a longitudinal cohort of aNSCLC patients with ALK-positive test (ALK+) who initiated ALKi between 1/1/2012 and 10/31/2018. The median time from ALK+ to ALKi was used to separate patients into early versus delayed treatment cohorts. Times from ALK+ to ALKi from the delayed cohort were sampled with replacement and used to create modified index dates among the early cohort. Cox proportional-hazards (CPH) modeling adjusting for patient baseline characteristics was performed on both original and modified cohorts to assess the impact of PTM on overall survival (OS).

      Results

      The median time from ALK+ to ALKi was 3 weeks among 422 patients meeting selection criteria. Decreased OS was observed in the delayed cohort both before (HR [95% CI]: 2.13 [1.19, 3.78]) and after (2.30 [1.28, 4.15]) PTM. Among patients receiving chemotherapy prior to ALK+, numerically better OS was observed prior to PTM for those who continued on chemotherapy after ALK+ before switching to ALKi versus those who switched right away (0.84 [0.37, 1.91]). However, this numerical difference disappeared after PTM (1.03 [0.44, 2.41]).

      Conclusions

      ITB can have a tangible impact on interpretation of results from survival studies. When the effect of early versus late treatment initiation is of interest, traditional methods to adjust for ITB have limited applicability. In such cases, PTM can provide meaningful results and should be considered by practitioners.