Lorbrena (lorlatinib)

Specifically, lorlatinib demonstrated superior efficacy in the Non-Asian subgroup (86.8%), patients without brain metastasis (84.7%), those with Eastern Cooperative Oncology Group performance status (ECOG PS) 0/1 (78.5%), males (71.2%), females (83.9%), patients aged < 65 years (74.3%), and never-smoking patients (89.7%)...Ensartinib achieved the optimal PFS in the Asian subgroup (71.8%)...Alectinib had the lowest hepatic and gastrointestinal AEs risk, while iruplinalkib had the lowest hematological AEs risk. https://www.crd.york.ac.uk/prospero/, identifier CRD42023495527.

Limited CIR beyond 12 months existed for brigatinib and ensartinib. Results from the Asian group's CIR aligned with global trials. Due to lower BM CIR, lorlatinib showed higher BM management cost savings compared to crizotinib and alectinib in Chinese 1 L patients.

This study provides a comprehensive functional atlas of ALK tyrosine kinase domain variants under TKI selection, offering a valuable experimental framework for interpreting resistance-associated variants. Although derived from in vitro models and therefore context dependent, this resource complements existing clinical and genomic knowledge and may aid in the functional interpretation of ALK variants observed in ALK-driven cancers.

P=N/A, N=20, Recruiting, Peking University Shenzhen Hospital

P=N/A, N=10, Not yet recruiting, Peking University Shenzhen Hospital; Peking University Shenzhen Hospital

From first-generation Crizotinib to third-generation Lorlatinib, successive agents have been refined for target selectivity, central nervous system penetration, and coverage of resistance-associated mutations, substantially improving patient survival and intracranial disease control. Nonetheless, the emergence of acquired resistance remains an overarching challenge, mediated by secondary kinase domain mutations, activation of bypass signaling pathways, and tumor phenotypic transformation. This review presents an integrative synthesis of ALK-targeted therapeutic developments, elucidates underlying resistance mechanisms, and surveys emerging strategies, providing a comprehensive perspective on current advances and future directions in precision management of ALK-driven malignancies.

Here, we report a case of an ALK-positive lung adenocarcinoma patient who developed resistance following sequential treatment with the ALK-TKI alectinib and lorlatinib, accompanied by histological transformation to LCNEC and concurrent genetic alterations including TP53 deletion, CDKN2A deletion, and MYC amplification. This case expands the spectrum of ALK-TKI resistance mechanisms and highlights the potential value of exploring combinatorial approaches incorporating immunotherapy, antiangiogenic therapy, and chemotherapy for the management of such cases.

Given lack of standard-of-care treatments for patients with actionable oncogenic alteration NSCLC transformed to SCLC, this remains a challenge and unmet need for treating these patients. Here, we present a case of a patient with ALK-rearranged NSCLC with transformation to SCLC, who has progressed on several lines of therapies and successfully treated with tarlatamab to elicit and maintain clinical benefit, including intracranial response.

The patient received whole-brain radiotherapy (30 Gy in 10 fractions), cisplatin-pemetrexed chemotherapy, and sequential targeted therapy with alectinib and lorlatinib. During three years of follow-up, MRI showed complete resolution of all lesions, and the patient remained neurologically intact and systemically stable. This case underscores the rarity of non-enhancing brain metastases in ALK-positive NSCLC and highlights the importance of recognizing this atypical imaging presentation for timely diagnosis and management.

A multifaceted approach is proposed for lung cancer patients receiving KI therapy to manage hyperlipidemia, minimize CVD risks, optimize treatment outcomes, and improve quality of life.

This first NSCLC-focused FAERS comparison integrating four-method signal detection with network analysis delineates reproducible class effects superimposed by drug-specific toxicities. Findings support tailored monitoring (e.g., dermatologic care for EGFR-TKIs; ECG/electrolytes for osimertinib; lipid/CK surveillance for ALK-TKIs; blood pressure/liver testing for RET-TKIs) to inform risk-aware first-line decisions.

P2, N=48, Active, not recruiting, Guangdong Provincial People's Hospital | Recruiting --> Active, not recruiting