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.

Although NTRK-associated fusions are significant in various cancers and have led to the development of targeted therapies, such as larotrectinib and entrectinib, the specific molecular impact of atypical PRUNE2::NTRK2 fusion remains unclear. The PRUNE2::NTRK2 gene fusions described here express a non-functional TrkB protein, and it is unclear whether the PRUNE2 function is intact or affected.

This presentation aligns with a case reported in Japan, describing severe hemolytic anemia with morphological changes in erythrocytes under alectinib treatment. This is the first report describing a rapid increase in hemoglobin after pausing alectinib and no relapse of hemolysis after switching to lorlatinib, while the lung cancer remained stable (stable disease).

The mechanism of lorlatinib-induced hyperglycemia is unclear but may involve reduced insulin secretion. This case underscores the importance of monitoring for hyperglycemia in patients receiving lorlatinib, even in the absence of pre-existing diabetes, to enable early detection and prevent life-threatening complications like DKA.

This case report identifies a novel SNX25-ROS1 fusion mutation in NSCLC, showing strong sensitivity to ROS1-targeted therapy. It highlights the importance of molecular profiling in detecting rare genetic alterations and underscores the therapeutic potential of targeted treatments for NSCLC with unique molecular subtypes.

Our study reveals a novel mechanism by which the NOTCH2-NTRK1 fusion confers resistance to osimertinib through its interaction with EGFR in NSCLC.