Real-World First-Line Alk Tki Comparisons in Alk-Positive Nsclc

Key Takeaways

• First-line ALK tyrosine kinase inhibitors were compared in a real-world retrospective cohort study of patients with ALK-positive non-small cell lung cancer in the United States.
• Outcomes included time-to-next treatment or death and overall survival, with propensity score-adjusted analyses used to compare treatment groups.
• Alectinib demonstrated significantly longer time-to-next treatment or death and overall survival compared with crizotinib, while lorlatinib showed potential benefit versus alectinib that did not reach statistical significance.

A real-world retrospective cohort study evaluated the comparative effectiveness of first-line ALK tyrosine kinase inhibitors in patients with ALK-positive non-small cell lung cancer. Using Optum’s de-identified Clinformatics Data Mart Database, investigators examined outcomes among patients treated in routine clinical practice between 2016 and 2024. The analysis focused on time-to-next treatment or death (TTNTD) and overall survival (OS), with propensity score-adjusted methods applied to support treatment comparisons.

The study included 940 patients who initiated first-line ALK TKI therapy. Treatment groups consisted of crizotinib (n=449), alectinib (n=417), brigatinib (n=30), ceritinib (n=8), and lorlatinib (n=36). Patients were eligible if they were at least 18 years of age, had lung cancer ICD-10 codes, received an ALK TKI, maintained continuous enrollment for at least six months before treatment initiation, and started therapy after the corresponding drug’s FDA approval.

In unadjusted analyses, alectinib demonstrated the longest median TTNTD at 33.5 months (95% CI, 24.6–46.3) and the longest median OS at 46.5 months (95% CI, 39.0–not reached). Overlap-weighted analyses showed that alectinib was associated with significantly longer TTNTD and OS compared with crizotinib. Specifically, the hazard ratio for TTNTD was 0.50 (95% CI, 0.41–0.61), and the hazard ratio for OS was 0.58 (95% CI, 0.47–0.71).

Comparisons between alectinib and lorlatinib numerically favored lorlatinib, although these findings did not achieve statistical significance. The overlap-weighted hazard ratio for TTNTD was 2.02 (95% CI, 0.92–4.46), and the hazard ratio for OS was 1.29 (95% CI, 0.58–2.83). Investigators noted that interpretation of these results was limited by the relatively small number of patients treated with lorlatinib and the resulting wide confidence intervals.

Taken together, the findings suggest that alectinib provides a clear survival advantage over crizotinib in routine clinical practice, consistent with results observed in clinical trials. Although lorlatinib demonstrated potential benefit compared with alectinib, additional data are needed to clarify comparative outcomes. As the largest claims-based analysis of first-line ALK TKIs reported to date, the study may help inform differentiation among agents that occupy similar positions in treatment guidelines.