Impact of Dosage Modifications on Efficacy: Insights from Select Tyrosine Kinase Inhibitors Approved for Treatment of Non-Small Cell Lung Cancer with EGFR Mutations.

Dose interruptions of four or more consecutive days in US FDA trial populations of NSCLC with EGFR mutations are more often linked to higher progression or death risk than dose reductions.

• Why it matters: Clinicians commonly adjust tyrosine kinase inhibitor dosing to manage adverse reactions, but the efficacy consequences of interruptions versus reductions are unclear.
• What they did: Using patient-level data from trials supporting original FDA approvals of afatinib, dacomitinib, mobocertinib, and osimertinib, investigators modeled daily dose received (DDR) with time-dependent Cox for PFS and landmark Cox models at 30, 60, and 90 days for PFS and OS.
• The result: Across these four monotherapies, the association between interruptions/reductions and death risk differed by drug, while interruptions were more often associated with worse outcomes, suggesting reductions may have less efficacy impact than missed treatment.

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