Xalkori (crizotinib)

The progression modes of ROS1 rearrangement may predict survival benefits and provide subsequent treatment strategies in ROS1-rearranged NSCLC.

Partial cystectomy was performed, but due to positive surgical margins and recurrent hematuria, targeted therapy with crizotinib was initiated based on anaplastic lymphoma kinase (ALK) positivity...This case highlights the importance of a multidisciplinary approach involving surgery, pathology, and oncology. Further pediatric-focused studies are warranted to refine treatment strategies and define long-term outcomes.

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.

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.

Molecular docking revealed high-affinity binding between tepotiniband all six hub targets (Vina scores: -8.0 to -10.6 kcal/mol), providing a structural basis for the postulated mechanistic link to AKI. These findings not only highlight the necessity for enhanced renal monitoring in tepotinib-treated patients but, more broadly, establish the FAERS-NetDock Pipeline as a reusable, generalizable and hypothesis-generating framework for evaluating tyrosine kinase inhibitors (TKIs)-induced nephrotoxicity; this framework is immediately applicable to profiling the safety of other TKIs (e.g. crizotinib, capmatinib, savolitinib, afatinib and osimertinib) and is readily adaptable for de-risking a wider spectrum of targeted therapies.

The condition exhibited a typical positive rechallenge feature of "discontinuation and recurrence," providing critical clinical evidence to establish this causal relationship. The case aims to enhance the understanding of crizotinib's metabolic side effects, underscores the importance of dynamic lipid monitoring, and offers empirical support for the standardized management of such rare adverse reactions.

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.

Crizotinib demonstrated clinical activity across tumors with METamp and METex14.Subprotocol C1, but not C2, met its primary endpoint. In METex14 disease, a read count cutoff >50,000 may help distinguish true pathogenic variants from low-level splice transcripts and enable more accurate classification.

Among two patients treated with crizotinib, PFS durations were 10.0 and 17.0 months, respectively...Although inflammatory markers did not consistently predict survival, abnormal values trended toward poorer outcomes. Larger multicenter studies are needed to clarify prognostic indicators and improve therapeutic strategies for this rare entity.

Current first-generation tyrosine kinase inhibitors (TKIs) such as crizotinib and entrectinib provide meaningful benefit but are limited by poor central nervous system (CNS) penetration and the development of resistance mutations, particularly G2032R. While its approval represents a significant advance for ROS1+ NSCLC, challenges remain, including resistance mechanisms such as L2086F, limited global access, and the absence of phase III confirmatory trials. Ongoing research into sequencing strategies, resistance profiling, and novel combination regimens will be essential to optimize patient outcomes.

The CROWN study demonstrated that first-line lorlatinib significantly improves progression-free survival and intracranial control compared to crizotinib, with sustained benefits observed over a follow-up period of up to 5 years. The proposed safety management framework emphasizes patient preparation and regular monitoring to predict AE occurrence, indicating AE-specific interventions, mitigation strategies and multidisciplinary collaboration to optimize outcomes. Lorlatinib's toxicity appears generally predictable and manageable; the safety framework offers pragmatic guidance to clinicians for appropriate management in clinical practice.

In summary, this study shows the critical role of selective targeting of components of the HIF1α signaling pathway for the complete eradication of chronic myeloid leukemia cells.