Lorbrena (lorlatinib)

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.

The study confirms the marked efficacy of ALK inhibitors in ALK-positive PMP, but highlights the need to monitor neurotoxicity in adolescent patients. Through analysis of the FN1(Fibronectin 1)-ALK fusion mechanism and literature review, this study emphasizes the importance of pathological differentiation, individualized treatment, and dynamic cognitive monitoring, providing insights for precision therapy in rare diseases.

This case underscores the importance of molecular profiling in diagnosing metastatic tumors and confirms lorlatinib as a highly effective first-line therapy for ALK-positive non-small cell lung cancer with atypical metastases.

This retrospective study included patients who developed CNS progression (time 0, [T0]) on alectinib, lorlatinib, brigatinib, or ensartinib. The median intracranial progression-free survival from T0 was not significantly different between the TKI-altered versus unaltered groups (p = 0.21). For patients with ALK-rearranged NSCLC with leptomeningeal progression or concurrent systemic progression, TKI change or dose increase was a feasible salvage strategy for CNS progression during treatment with CNS-penetrable TKI.

Here, we present a patient diagnosed with high grade metastatic inflammatory myofibroblastic tumor driven by a RANBP2::ALK fusion, who later developed an ALK G1202R resistance mutation in the setting of treatment with crizotinib. The patient remains without evidence of disease now 18 months after discontinuing adjuvant lorlatinib. This case illustrates the importance of serial molecular profiling to guide selection of the optimal ALK inhibitor for the best clinical outcomes.

Herein, we report a case of lung adenocarcinoma harboring ALK deletions of exons 6-20 that responded to alectinib and lorlatinib treatment...Despite the high expression of programmed death ligand 1 (PD-L1) (tumor proportion score: 95%), the response to pembrolizumab and chemotherapy was limited...This case suggests that ALK internal deletions, even those affecting exon 20, demonstrate oncogenic potential and sensitivity to ALK inhibitors. ALK IHC remains an essential complementary test in cases of high clinical suspicion and inconclusive results using initial molecular testing.

This real-world analysis highlighted durable effectiveness of lorlatinib in treating NSCLC patients with ROS1 rearrangements in second-line and beyond settings. The safety profile aligned with previous clinical and real-world studies.