Larotrectinib was used in 142 patients, demonstrating an 83.80% response rate, with low mortality (2.82%) and recurrence (2.11%) rates. Entrectinib had a lower response rate of 63.64%. We confirm the rarity of NTRK1-3 fusions in sarcomas. TRK inhibitors show high efficacy in sarcomas, emphasizing the necessity of genomic testing in all cases.Protocol registration: https://www.crd.york.ac.uk/PROSPERO/view/CRD42024563594.

P2, N=48, Recruiting, Guangdong Provincial People's Hospital | Trial completion date: Dec 2026 --> Apr 2026 | Trial primary completion date: Dec 2024 --> Dec 2025

This case highlights the essential role of DNA methylation profiling in resolving diagnostic ambiguity and guiding targeted treatment in CNS tumors. It further supports the potential efficacy of entrectinib in NTRK fusion-positive glioneuronal tumors.

P2, N=6, Terminated, M.D. Anderson Cancer Center | N=58 --> 6 | Trial completion date: Dec 2027 --> Dec 2025 | Recruiting --> Terminated | Trial primary completion date: Dec 2027 --> Dec 2025; <75% Participation

Despite the higher grade ≥3 AE incidence, similar rates of dose reduction, interruption, or discontinuation suggest these AEs are manageable. Lorlatinib remains a first-line treatment option for ALK+ metastatic non-small cell lung cancer, offering meaningful benefits to appropriate patients.

These findings underscore the importance of routine cardiovascular monitoring, particularly in older patients and those with atrial arrhythmias.

Transition to lorlatinib was associated with extended survival in both groups, reflecting its use as a later-line therapy following resistance. Alectinib demonstrated superior disease control in terms of PFS. Further research is warranted to optimize treatment sequence strategies for ALK inhibitors.

We report a case of mandibular ssRMS with FUS-TFCP2 fusion treated with the third-generation ALK inhibitor Lorlatinib, resulting in a marked clinical response. We also review the potential utility of ALK-targeted therapies in managing FUS-TFCP2 fusion-positive ssRMS and support further exploration of ALK inhibition in this subset.

Among the patient-reported outcomes, different domains of quality of life improved. This case may represent the backbone for further interventional studies aimed at determining the real efficacy of exercise intervention in preventing or controlling weight gain in this population.

These results, along with the extended intracranial efficacy and consistent safety profile of long-term lorlatinib treatment, are unprecedented in patients with ALK-positive mNSCLC. This Grand Rounds article summarizes the efficacy, safety, and tolerability of lorlatinib after 5 years and includes a fictional patient case to demonstrate how advanced practice providers contribute to personalized patient care and the identification and management of adverse events.

Despite an initial 13 kg weight gain over 9 months, split between fat and lean mass, subsequent fat loss (~3.5 kg) occurred while lean mass was preserved. This case suggests that prolonged, structured exercise is a safe and feasible strategy to attenuate entrectinib-associated metabolic effects and support physical function during targeted therapy in advanced NSCLC.

This analysis demonstrates continued efficacy of entrectinib in Asian patients with advanced ROS1-fp NSCLC, both overall and in the 1L setting. No new safety signals emerged.