Lorbrena (lorlatinib)

P=N/A, N=24, Recruiting, Centro de Tratamiento e Investigación sobre Cáncer, Luis Carlos Sarmiento Angulo

Despite robust evidence supporting ALK-targeted therapies, this study highlights substantial disparities in access to diagnostics and treatment for ALK-rearranged NSCLC in Brazil, particularly among patients reliant on the public health care system. Findings underscore the need for policies to strengthen testing infrastructure, ensure equitable access to guideline-recommended therapies, and enhance provider education. Addressing these gaps is essential for equitable precision oncology and improved outcomes.

Although rare, GI perforation, represents a clinically relevant adverse event associated with alectinib, particularly in patients with diverticulosis or other predisposing conditions. It is essential to optimize safety and long-term disease control by raising awareness of early warning symptoms, conducting a baseline GI evaluation in high-risk patients and carefully sequencing therapy after discontinuation.

A 63-year-old female underwent radical resection for stage IA lung adenocarcinoma (ALK-positive) and received adjuvant ensartinib...The patient was subsequently treated with lorlatinib combined with stereotactic radiotherapy...This case highlights that during long-term follow-up of patients with malignancies, a new intracranial lesions may warrant consideration of a second primary cancer (SPC), particularly when the treatment response is not consistent with the expected biology of the original tumor. Timely pathological confirmation and multidisciplinary review may help reduce diagnostic delay and improve treatment selection.

P1, N=102, Not yet recruiting, Chugai Pharmaceutical

With median PFS yet to be reached after 7 years of follow-up in CROWN, lorlatinib continues to show unprecedented long-term benefit in patients with advanced ALK-positive NSCLC. Patients without progression within 24 months on lorlatinib have a low risk of progression or death at year 7 and may continue long-term treatment. Findings suggest that sustained long-term disease control with first-line lorlatinib may enable advanced ALK-positive NSCLC to evolve toward a chronic condition.

For EGFR-mutant NSCLC, sequential development of tyrosine kinase inhibitors (TKIs) from first- to third-generation agents-culminating in osimertinib-has markedly improved survival. Similarly, successive generations of ALK inhibitors, including alectinib, brigatinib, and lorlatinib, have extended disease control, particularly within the central nervous system. The introduction of antibody-drug conjugates (ADCs), such as trastuzumab deruxtecan for HER2-mutant NSCLC, and emerging TKIs like zongertinib, represent new therapeutic milestones...Beyond lung cancer, our group, in collaboration with Juntendo University ARO (academic research organization) and fifteen institutions in Japan, conducted the MARBLE phase II trial of atezolizumab plus chemotherapy for thymic carcinoma, achieving a 56% objective response rate and 9.6-month median progression-free survival, supporting potential ICI approval in Japan...The DLL3-targeted BiTE tarlatamab significantly improved overall survival to 13.6 months in the phase III DeLLphi-304 trial for relapsed SCLC, with manageable cytokine release syndrome. Collectively, these advances signify a shift toward biologically driven, molecular-targeted or immune-integrated therapy, aiming to transform lung cancer into a chronic, manageable disease in the future, hopefully.

Collectively, these findings demonstrate that ALK inhibition confers neuroprotection by modulating microglia-mediated neuroinflammation. Given that LOR is a clinically approved anticancer drug with blood-brain barrier permeability, this study provides experimental evidence supporting its repositioning for the treatment of neuroinflammatory disorders, such as PD.

Not available.

This study establishes a promising ZNF-based prognostic model for LUAD, providing a potential tool for risk stratification and individualized therapeutic decision-making. The identification of FGD3 as a potential mediator of drug resistance highlights its promise as a candidate biomarker and therapeutic target in LUAD.

Oncologists should consider broad next-generation sequencing, including fusion detection, for patients with KRAS-wildtype PDAC. When an ALK fusion is identified, ALK inhibitor therapy can yield durable disease control.

Herein, we report a case of an elderly patient with ALK-rearrangement and exceptionally high PD-L1 expression (TPS ≥ 95%) NSCLC who experienced disease progression following first-line lorlatinib with genetically confirmed MET amplification. The patient subsequently received an exploratory combination of continued lorlatinib plus envafolimab and achieved partial response (PR) with manageable tolerability after 4 months, highlighting a potential sequential strategy that may warrant further investigation in select ALK-positive NSCLC patients exhibiting both bypass pathway activation and exceptionally high PD-L1 expression.