ALK rearrangement

P1, N=40, Recruiting, University Health Network, Toronto | Trial primary completion date: Dec 2025 --> Aug 2026

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.

Currently, molecular analyses guide treatment decisions in advanced cases following discussions in molecular tumour boards. Therefore, the classification of subtypes, together with their specific molecular alterations and signalling pathways, is gaining importance not only for targeted systemic therapy but also for the identification of patients with a hereditary tumour syndrome.The task of pathologists is to identify new tumour entities and genetically inherited tumour forms in order to ensure the best possible clinical care for patients.

These findings suggest that targeted therapy for recurrence is a valuable treatment strategy. Prospective studies are warranted to determine the optimal timing for ALK-TKI initiation.

Biomarker discovery advances with a new assay enabling the use of miRNAs for non-invasive diagnosis and staging of metabolic dysfunction-associated steatotic liver disease (MASLD). Finally, an optimized elastase assay improves FISH-based detection of ALK gene rearrangements, enhancing diagnostic accuracy in non-small cell lung cancer (NSCLC).

The first metastatic site in NSCLC follows histology-specific patterns, with adenocarcinoma favoring hematogenous spread and squamous carcinoma showing locoregional involvement. Molecular status further refines these patterns in adenocarcinoma. Incorporating histology into baseline staging may improve diagnostic efficiency and prognostic accuracy.

Initial treatment with chemoimmunotherapy was complicated by hypersensitivity reactions to nivolumab and paclitaxel, leading to a brief hospitalization...This case demonstrates the efficacy of neoadjuvant alectinib in managing ALK-mutant stage III lung adenocarcinoma, highlighting the potential benefits of targeted therapy in the neoadjuvant setting. Further studies are needed to establish optimal treatment protocols for patients with ALK-positive lung cancer.

This case presents the diagnostic challenges in ALK-positive neoplasms. Superficial soft tissue tumors associated with ALK include a heterogeneous group of lesions that may share similar morphological features. We believe that a generic term, ALK-Rearranged Superficial Mesenchymal Neoplasms (ARSMN), may serve as a more inclusive diagnostic label for these entities in routine pathology practice.

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.

P1/2, N=862, Recruiting, DualityBio Inc. | Trial completion date: Jan 2028 --> May 2028 | Trial primary completion date: Sep 2027 --> Dec 2027

Sensitivity analyses confirmed that none of the ALK inhibitors were cost-effective compared to chemotherapy. The five-year BIA estimated the budget impact of ceritinib (450 mg/day, 750 mg/day), alectinib (600 mg/day, 1,200 mg/day), and brigatinib at 2,345 (63.81), 3,703 (100.76), 9,830 (267.49), 19,328 (525.92), and 9,502 (258.56) million THB (USD), respectively.

The mortality rate associated with refractory TKI-ILD is substantial. Dyspnea, LDH >420 U/L at TKI-ILD onset, and DAD radiographic pattern are independent risk factors that may aid in identifying refractory TKI-ILD cases.