WCLC 2025 - Posters & ePosters-EP.12.10 Clinical Investigators’ (CIs) Preferences for First-Line Therapy of ALK-Positive Metastatic Non-Small Cell Lung Cancer

EP.12.10 Clinical Investigators’ (CIs) Preferences for First-Line Therapy of ALK-Positive Metastatic Non-Small Cell Lung Cancer

Back to course

Pdf Summary

This survey study, conducted in March 2025 among 20 US-based and international clinical investigators (CIs), assessed preferences for first-line therapy in ALK-positive metastatic non-small cell lung cancer (mNSCLC). With six FDA-approved ALK inhibitors available and limited head-to-head comparison trials, clinicians often rely on clinical and practical factors to guide treatment choice.<br /><br />Key findings include a general preference for lorlatinib over alectinib in a 60-year-old asymptomatic patient with ALK mNSCLC and no comorbidities (PD-L1 TPS 0). Lorlatinib was also favored for patients with multiple bilateral brain metastases needing whole-brain radiation, reflecting its superior central nervous system (CNS) activity as perceived by all surveyed CIs. Indeed, lorlatinib was widely regarded as the most efficacious ALK inhibitor in the first-line setting, while alectinib was considered the most tolerable agent.<br /><br />In patients with various comorbidities—such as hypertension, diabetes, anxiety/depression, bradycardia, or chronic kidney disease on dialysis—opinions varied, but lorlatinib still remained the preferred choice for at least half of the clinicians. For older patients (age 80 without comorbidities), preferences split evenly between lorlatinib and alectinib, suggesting that age and patient health greatly influence treatment decisions.<br /><br />Despite lorlatinib’s efficacy, CIs estimated a higher likelihood of dose interruptions or reductions (median 50%) and permanent discontinuation (median 10%) compared to alectinib (20% and 5%, respectively), reflecting lorlatinib’s reduced tolerability.<br /><br />In conclusion, the survey highlights a predominant preference for lorlatinib in first-line treatment of ALK-positive mNSCLC driven by its efficacy and CNS penetration, balanced against its tolerability profile. Treatment decisions are nuanced and influenced by patient age and comorbidities. Further research is needed to understand decision-making among community oncologists managing these patients.

Asset Subtitle

Neil Love

Meta Tag

Speaker Neil Love

Topic Metastatic Non-small Cell Lung Cancer – Targeted Therapy

Keywords

ALK-positive NSCLC

lorlatinib

alectinib

first-line therapy

brain metastases

CNS activity

clinical investigators

tolerability

comorbidities

treatment preferences