Lorlatinib as a treatment for ALK-positive lung cancer

Baba, Keisuke; Goto, Yasushi

doi:10.2217/fon-2022-0184

Cited by 10 publications

(6 citation statements)

References 163 publications

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“…Considering the clinical safety concerns and cost constraints associated with lorlatinib, its use in the clinic remains restricted. Hence, establishing the optimal sequencing and combination of ALK inhibitors for patients is crucial (38,39). There are several limitations in the present study.…”

Section: Discussionmentioning

confidence: 86%

Efficacy and survival outcomes of alectinib vs. crizotinib in ALK‑positive NSCLC patients with CNS metastases: A retrospective study

Liu,

Fu,

Guo

et al. 2024

Oncol Lett

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Anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKIs) have transformed the treatment paradigm for patients with ALK-positive non-small cell lung cancer (NSCLC). Yet the differential efficacy between alectinib and crizotinib in treating patients with NSCLC and central nervous system (CNS) metastases has been insufficiently studied. A retrospective analysis was conducted of clinical outcomes of patients with ALK-positive NSCLC and CNS metastases treated at the Shandong Cancer Centre. Based on their initial ALK-TKI treatment, patients were categorised into either the crizotinib group or the alectinib group. Efficacy, progression-free survival (PFS), intracranial PFS and overall survival (OS) were evaluated. A total of 46 eligible patients were enrolled in the present study: 33 patients received crizotinib and 13 patients received alectinib. The median OS of the entire group was 66.8 months (95% CI: 48.5-85.1). Compared with the patients in the crizotinib group, the patients in the alectinib group showed a significant improvement in both median (m)PFS (27.5 vs. 9.5 months; P=0.003) and intracranial mPFS (36.0 vs. 10.8 months; P<0.001). However, there was no significant difference in OS between the alectinib and crizotinib groups (not reached vs. 58.7 months; P=0.149).Furthermore, there were no significant differences between patients receiving TKI combined with radiotherapy (RT) vs. TKI alone with respect to mPFS (11.0 vs. 11.7 months, P=0.863) as well as intracranial mPFS (12.5 vs. 16.9 months, P=0.721).In the present study, alectinib exhibited superior efficacy to crizotinib for treating patients with ALK-positive NSCLC and CNS metastases, especially in terms of delaying disease progression and preventing CNS recurrence. Moreover, the results demonstrated that it might be beneficial to delay local RT for patients with ALK-positive NSCL and CNS metastases.

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Section: Discussionmentioning

confidence: 86%

Efficacy and survival outcomes of alectinib vs. crizotinib in ALK‑positive NSCLC patients with CNS metastases: A retrospective study

Liu,

Fu,

Guo

et al. 2024

Oncol Lett

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“…A series of ALK-TKIs, including crizotinib, ceritinib, alectinib, brigatinib, ensartinib, and lorlatinib, have been approved for ALK-positive patients worldwide. More specifically, crizotinib, ceritinib, and lorlatinib work as ATP-competitive inhibitors ( 100 – 102 ); alectinib and brigatinib can inhibit ALK protein by preventing phosphorylation ( 103 ); ensartinib acts by inhibiting ALK fusions engineered to have point mutations ( 104 ).…”

Section: Targeted Therapy Resistance In Nsclcmentioning

confidence: 99%

Mechanisms of resistance to targeted therapy and immunotherapy in non-small cell lung cancer: promising strategies to overcoming challenges

Xiang,

Liu,

Wang

et al. 2024

Front. Immunol.

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Resistance to targeted therapy and immunotherapy in non-small cell lung cancer (NSCLC) is a significant challenge in the treatment of this disease. The mechanisms of resistance are multifactorial and include molecular target alterations and activation of alternative pathways, tumor heterogeneity and tumor microenvironment change, immune evasion, and immunosuppression. Promising strategies for overcoming resistance include the development of combination therapies, understanding the resistance mechanisms to better use novel drug targets, the identification of biomarkers, the modulation of the tumor microenvironment and so on. Ongoing research into the mechanisms of resistance and the development of new therapeutic approaches hold great promise for improving outcomes for patients with NSCLC. Here, we summarize diverse mechanisms driving resistance to targeted therapy and immunotherapy in NSCLC and the latest potential and promising strategies to overcome the resistance to help patients who suffer from NSCLC.

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“…Lorlatinib (10 mg/kg) can significantly inhibit transplanted tumor growth in the tissue-derived mouse model of tumor transplantation, and tumor can also significantly decline when lorlatinib is replaced after crizotinib resistance. In an intracranial mouse transplant tumor model, lorlatinib significantly inhibited internal tumor growth and significantly prolonged mouse survival [96][97][98].…”

Section: Alk Inhibitorsmentioning

confidence: 99%

Review of Personalized Medicine and Pharmacogenomics of Anti-Cancer Compounds and Natural Products

Zhou¹,

Peng²,

Wang³

et al. 2023

Preprint

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In recent years, the FDA has approved numerous antitumor drugs that are mutation-based for clinical use. These drugs have improved the precision of treatment and reduced adverse effects and side effects. Personalized therapy is a prominent and hot topic of current medicine and also represents the future direction of development. With the continuous advancements in gene sequencing and high-throughput screening, research and development strategies for personalized clinical drugs have developed rapidly. This review elaborated the recent personalized treatment strategies, which include artificial intelligence, multi-omics analysis, chemical proteomics, and computation aided drug design. These technologies rely on the molecular classification of diseases, the global signaling network within organisms, and new models for all targets, which significantly support the development of personalized medicine. Meanwhile, we summarized chemical drugs such as lorlatinib, osimertinib, and other natural products that deliver personalized therapeutic effects based on genetic mutations. This review also highlights potential challenges in interpreting genetic mutations and combining drugs, while providing new ideas for the development of personalized medicine and pharmacogenomics in cancer study.

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Lorlatinib as a treatment for ALK-positive lung cancer

Cited by 10 publications

References 163 publications

Efficacy and survival outcomes of alectinib vs. crizotinib in ALK‑positive NSCLC patients with CNS metastases: A retrospective study

Efficacy and survival outcomes of alectinib vs. crizotinib in ALK‑positive NSCLC patients with CNS metastases: A retrospective study

Mechanisms of resistance to targeted therapy and immunotherapy in non-small cell lung cancer: promising strategies to overcoming challenges

Review of Personalized Medicine and Pharmacogenomics of Anti-Cancer Compounds and Natural Products

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