Opinion|Videos|March 21, 2025
Latest Advances in Management of Advanced NSCLC with ALK or ROS1 Mutations
Panelists discuss how the 5-year follow-up data from the CROWN trial support lorlatinib as a frontline treatment for ALK-positive non–small cell lung cancer NSCLC with brain metastasis. For frontline therapy, starting at full dose is preferred, adjusting if needed. Post progression, lorlatinib can be continued or combined with other agents. Biomarker testing for ROS1 is essential, with recent data (TRIDENT-1 trial) favoring lorlatinib for ROS1-positive central nervous system (CNS) involvement. Novel agents like taletrectinib and zidesamtinib from TRUST-I/II and ARROS-1 trials show promise in expanding treatment options for ROS1-positive NSCLC.
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Video content above is prompted by the following:
- Briefly comment on the 5-year follow-up data from the CROWN trial and discuss how these findings inform your first-line treatment approach and in managing ALK-positive NSCLC with brain metastasis. (Solomon BJ, et al. J Clin Oncol. 2024;42(29):3400-3409.)
- Do you prefer starting patients at the full dose with subsequent dose reductions if necessary, or initiating at a lower dose and titrating upward as tolerated?
- For patients receiving lorlatinib in the frontline setting, how do you manage treatment following disease progression?
- Briefly discuss your approach to biomarker testing for ROS1 alterations and how recent data inform your treatment decisions in this space.
- How do the latest data from TRIDENT-1 trial inform your treatment approach for patients with ROS1 alterations and CNS involvement? (Drilon A, et al. NEJM. 2024;390:118-131.)
- Briefly comment on the TRUST-I/II (Perol, M et al. ESMO 2024. Abs 1289P) and ARROS-1 (Besse B, et al. ESMO 2024. Abs 1256MO) trials. Where do you see these novel agents (eg, taletrectinib and zidesamtinib) fitting in the treatment paradigm?
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