Lorbrena (lorlatinib)

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.

First-generation tyrosine kinase inhibitors (TKIs) such as crizotinib displayed significant early reactions but faced challenges due to restricted central nervous system (CNS) penetration and mutation resistance, while entrectinib and larotrectinib expanded treatment options but also experienced resistance...Safety data shows an acceptable toxicity profile, mainly featuring gastrointestinal and hepatic adverse effects, with fewer neurocognitive side effects compared to lorlatinib...Current trials and regulatory activities in China, the U.S., and other locations demonstrate taletrectinib's growing clinical significance. Taletrectinib's well-rounded pharmacological attributes of systemic action, intracranial effectiveness, resistance range, and tolerability render it an intriguing enhancement to the framework of precision oncology.

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.

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 study is by far the most comprehensive systematic review and meta-analysis on HRQoL among ALK-positive NSCLC patients treated with ALK-TKIs. These findings extended prior literature by conducting a granular comparison of all available ALK-TKIs across multiple endpoints and highlighted the improved performance of next-generation ALK-TKIs in enhancing HRQoL for ALK-positive NSCLC patients.

Crizotinib, entrectinib, and repotrectinib have been approved by the US Food and Drug Administration for treatment of ROS1-positive NSCLC. In this nonrandomized clinical trial, lorlatinib demonstrated durable efficacy and manageable safety in TKI-naive advanced ROS1-positive NSCLC, supporting the potential for using lorlatinib in earlier treatment settings. ClinicalTrials.gov Identifier: NCT03612154.

Crizotinib first demonstrated substantial clinical benefit, but its limitations, including poor central nervous system (CNS) penetration and acquired resistance, highlighted the need for next-generation inhibitors. Several agents have since been developed, including entrectinib, lorlatinib, repotrectinib, taletrectinib, and zidesamtinib, each offering improved intracranial (IC) activity and efficacy against resistance mutations, notably ROS1^G2032R. Despite these advances, optimal sequencing strategies remain undefined, and resistance ultimately emerges in most patients. This review provides an updated overview of ROS1 biology, diagnostic approaches, clinical outcomes with currently available TKIs, mechanisms of resistance, and ongoing challenges, emphasizing the rapidly evolving therapeutic landscape.

This is the first reported case of concurrent alectinib and cytotoxic chemotherapy during pregnancy, successfully used in the setting of progressive ALK-rearranged NSCLC. The placental findings align with observations in pregnancies complicated by FGR. This case highlights the potential feasibility and safety of intensification of systemic therapy during pregnancy, and underscores the importance of individualised multi-disciplinary care.