2024 World Conference on Lung Cancer (WCLC) - Posters-P1.12B.10 Dose Adjustments and Exposure-Response Associated with Selpercatinib in Patients with Advanced NSCLC

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The study presented at the 2024 IASLC World Conference on Lung Cancer explores dose adjustments and exposure-response associations of selpercatinib in patients with advanced non-small cell lung cancer (NSCLC). Selpercatinib, a selective oral RET kinase inhibitor, has shown consistent clinical benefit in trials LIBRETTO-001 and LIBRETTO-431, including high response rates and a median progression-free survival (PFS) of approximately two years. This investigation aimed to assess whether clinical benefits are maintained with lower drug exposure due to dose reductions applied to manage side effects.<br /><br />Approximately half of the NSCLC cohort experienced treatment-emergent adverse events (TEAEs) necessitating dose reductions from an initial selpercatinib dose of 160 mg twice daily to as low as 40 mg. Findings showed no significant relationship between drug exposure and PFS, suggesting no detrimental effects on survival from dose adjustments. However, higher drug exposure was linked with improved response rates, indicating potential therapeutic benefits with higher dosing.<br /><br />The study concluded that selpercatinib can provide ongoing clinical benefits even with reduced dosing to manage toxicity, without negatively impacting PFS. This is critical for optimizing treatment regimens and enhancing patient adherence. Therefore, patients on selpercatinib should be closely monitored for toxicity with individualized dose adjustments to maximize therapeutic outcomes. Such dose management may ensure continued efficacy, particularly in situations where side effects might otherwise limit treatment adherence. <br /><br />The research underscores the tailored use of selpercatinib in NSCLC, advocating for strategic dose adjustments based on patient tolerance, as indicated by ongoing phase 1/2 and phase 3 trials. Patient characteristics, such as age, body weight, and prior therapies, were considered within a population pharmacokinetic model to help guide dose optimization strategies.

Asset Subtitle

Keunchil Park

Meta Tag

Speaker Keunchil Park

Topic Metastatic NSCLC – Targeted Therapy

Keywords

selpercatinib

NSCLC

dose adjustments

RET kinase inhibitor

LIBRETTO trials

progression-free survival

adverse events

drug exposure

therapeutic outcomes

pharmacokinetic model