Next-Generation TKIs Show Similar Real-World Outcomes and Costs in ALK-Positive mNSCLC

Key Takeaways:

• In a real-world comparison of alectinib, brigatinib, and lorlatinib, no notable differences were observed in clinical outcomes among patients with anaplastic lymphoma kinase (ALK)-positive metastatic non–small cell lung cancer (mNSCLC), indicating comparable efficacy.
• Researchers found no significant differences in all-cause health care utilization or care costs between cohorts, which suggests alectinib, brigatinib, and lorlatinib have similar rates of economic burden.
• Further research is needed to support these findings and provide more real-world evidence on the effectiveness of next-generation tyrosine kinase inhibitors (TKIs).

The TKIs alectinib, brigatinib, and lorlatinib have been approved by the US Food and Drug Administration (FDA) to treat patients with ALK-positive mNSCLC.

While next-generation TKIs are more potent than and effective than crizotinib, research directly comparing their real-world clinical outcomes and care costs is limited.

Study Methods and Outcomes

In order to provide evidence to support treatment decision-making, researchers compared the clinical and economic outcomes of alectinib, brigatinib, and lorlatinib. Using Veradigm electronic health records and claims data from the Komodo database, the study identified patients with ALK-positive mNSCLC who initiated treatment with alectinib, brigatinib, or lorlatinib between May 2020 and December 2024.

Real-world clinical outcomes included time to treatment discontinuation (TTD), time to next treatment (TTNT), progression-free survival (PFS), and overall survival (OS).

Real-world economic outcomes included all-cause health care utilization and total care costs.

Treatment Patterns and Clinical Outcomes

Of the 481 patients included in the study, 391 received alectinib, 32 received brigatinib, and 58 received lorlatinib.

The average time between initial diagnosis and treatment initiation was 40 days for the alectinib cohort, 58 days for the brigatinib cohort, and 217 days for the lorlatinib cohort. Average follow-up times were 506, 591, and 355 days, respectively.

The safety profile for next-generation TKIs was similar to that of previous clinical trials. Cough was the most common adverse event across all 3 cohorts, followed by fatigue.

Weighted analyses found no significant differences in TTD, TTNT, PFS, or OS between cohorts. However, these findings should be interpreted with caution due to the study’s wide confidence intervals, small sample sizes, and limited follow-up.

Economic Outcomes

Similar to the study’s clinical outcomes, no notable differences in all-cause health care utilization or care costs were observed.

Average weighted care costs per-patient-per-month (PPPM) for alectinib, brigatinib, and lorlatinib were $20 873, $25 693, and $24 984, respectively.

Implications for Managed Care

This study provides initial real-world evidence on the clinical effectiveness and economic burden of next-generation TKIs to help inform treatment decisions for patients with ALK-positive mNSCLC.

The authors said, “These findings indicate that, in routine clinical practice, evidence does not yet support differentiating treatment choice based on real-world clinical outcomes or treatment costs. Studies with larger sample sizes and extended follow-up are needed.”

Reference

Malhotra J, Marchlewicz EH, Zhang Y, et al. Real-world clinical and economic consequences of next-generation anaplastic lymphoma kinase-positive (ALK +) tyrosine kinase inhibitors (TKIs) in patients with TKI-naïve ALK + metastatic non-small cell lung cancer in the United States. Adv Ther. 2026. doi:10.1007/s12325-026-03679-0