Lorbrena (lorlatinib)

Molecular Mechanics Poisson-Boltzmann Surface Area (MM/PBSA) calculations further confirmed that yibeinoside A and vomicine had better binding free energies than lorlatinib. Collectively, these findings suggest that yibeinoside A, with its balanced binding interactions and favorable predicted pharmacokinetic profile, is a promising lead candidate for further development as a selective inhibitor against G2032R-mutant ROS1.

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.

The patient was initially treated with alectinib, but experienced rapid disease progression. After repeat genetic testing, therapy was switched to lorlatinib, which again resulted in early progression...To our knowledge, this is the first reported case of ivonescimab use in such a patient. This case offers a potential reference for the management of ALK fusion-positive lung adenocarcinoma resistant to ALK tyrosine kinase inhibitors (ALK-TKIs).

In contrast, permanent discontinuation was associated with higher weight/BSA in brigatinib/ceritinib/crizotinib-treated patients. Higher weight and larger BSA at the start of ALK TKI treatment were associated with higher likelihood of toxicity, leading to more DRs and TIs-particularly in males and patients receiving alectinib and lorlatinib. However, weight and BSA were not associated with treatment outcomes.

Lorlatinib, a third-generation ALK TKI, achieved 1L indication on March 3, 2021, but is generally associated with adverse events including weight gain in up to 44% of patients from the recent update of the CROWN study; hence its use as 1L treatment has lagged behind alectinib. Here, we report a patient's case who had gained significant weight during still on-going 12-year treatment with alectinib and achieved weight loss through semaglutide but discontinued several months after starting semaglutide due to acute gallstone pancreatitis requiring emergency cholecystectomy. We believe this is the first case report on the efficacy and potential adverse events of GLP-1 agonist in treating the weight gain induced by alectinib.

At 2 years of follow-up, the patient remains on lorlatinib therapy without recurrence and demonstrates excellent hand function despite moderate scar contractures. This case highlights the efficacy of neoadjuvant therapy combined with resection in managing infantile fibrosarcoma-like tumors.

P2, N=70, Active, not recruiting, CStone Pharmaceuticals | Trial completion date: Nov 2025 --> May 2026

Despite the higher grade ≥3 AE incidence, similar rates of dose reduction, interruption, or discontinuation suggest these AEs are manageable. Lorlatinib remains a first-line treatment option for ALK+ metastatic non-small cell lung cancer, offering meaningful benefits to appropriate patients.

P2, N=48, Recruiting, Guangdong Provincial People's Hospital | Trial completion date: Dec 2026 --> Apr 2026 | Trial primary completion date: Dec 2024 --> Dec 2025

These findings underscore the importance of routine cardiovascular monitoring, particularly in older patients and those with atrial arrhythmias.

Transition to lorlatinib was associated with extended survival in both groups, reflecting its use as a later-line therapy following resistance. Alectinib demonstrated superior disease control in terms of PFS. Further research is warranted to optimize treatment sequence strategies for ALK inhibitors.

First-generation tyrosine kinase inhibitors (TKIs) such as crizotinib displayed significant early reactions but faced challenges due to restricted central nervous system (CNS) penetration and mutation resistance, while entrectinib and larotrectinib expanded treatment options but also experienced resistance...Safety data shows an acceptable toxicity profile, mainly featuring gastrointestinal and hepatic adverse effects, with fewer neurocognitive side effects compared to lorlatinib...Current trials and regulatory activities in China, the U.S., and other locations demonstrate taletrectinib's growing clinical significance. Taletrectinib's well-rounded pharmacological attributes of systemic action, intracranial effectiveness, resistance range, and tolerability render it an intriguing enhancement to the framework of precision oncology.