Lorlatinib in Crisotinib-Resistant Alk+ NSCLC Patients. Our Result

Introduction. Lorlatinib is a third generation ALK tyrosine kinase inhibitor. Back in 2018, the drug underwent accelerated FDA approval and was recommended for the treatment of patients with ALK-positive non-small cell lung cancer after progression on crizotinib and another ALK inhibitor. For a long time, the use of the drug in Russia was possible only in clinical trials or expanded access program. However, now this drug is becoming available in our country.Purpose. To analyze the overall and intracranial response during lorlatinib therapy, as well as the tolerability of lorlatinib therapy in patients with ALK-positive non-small cell lung cancer who previously received crizotinib and one or more lines of cytostatic therapy.Materials and methods. The study included 39 patients aged 28 to 76 years, diagnosed with non-small cell lung cancer. In 36 cases, a translocation in the ALK gene was detected, in three, a ROS1 translocation. All patients received targeted therapy with crizotinib and one or more lines of chemotherapy before starting lorlatinib therapy. All patients received 100 mg lorlatinib therapy until disease progression or intolerable toxicity.Results. During the observation period for the moment of September 2021, an objective response was achieved in 28 patients (71.7%), in 10 patients (25.6%) – stabilization of the disease, in one patient (2.6%) – progression. The median duration of the drug was just over 40 months. The drug intake was characterized by a predictable and manageable toxicity profile.Conclusions. These data indicate a high direct efficacy of lorlatinib in patients with ALK/ROS1 translocations. The data obtained do not contradict the results obtained in the course of clinical trials. The drug lorlatinib has currently received registration in Russia for the treatment of non-small cell lung cancer in cases of the development of progression while taking secondgeneration ALK inhibitors or several lines of therapy with ALK inhibitors.

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Efficacy of lorlatinib in the treatment of ALK-positive non-small cell lung cancer patients with progression on crizotinib: personal experience

Лактионов

Реутова

Kruteleva

et al. 2021

Medicinskij sovet

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Lorlatinib: new therapeutic options for ALK-positive patients

Реутова

2022

Medicinskij sovet

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In less than 10 years, the standard of drug therapy for non-small cell lung cancer (NSCLC) has changed tremendously. The emphasis on a personalized approach in the choice of treatment tactics in patients with advanced NSCLC yields tangible results. The identification of patients with activating mutations and the administration of targeted therapy to them has significantly improved the results of treatment. Translocations in the ALK gene are classified as rare mutations. As a rule, these are quite young people, non-smokers or with little experience of smoking. One of the characteristic features of ALK-positive NSCLC is frequent metastasis to the CNS, so one of the important criteria for the effectiveness of new drugs is the assessment of their intracranial activity. Lorlatinib is a thirdgeneration tyrosine kinase (TKI) ALK that penetrates the blood-brain barrier well and has a wide spectrum of antitumor activity against most known resistance mutations that appear during targeted therapy with crizotinib and second-generation TKI. Like its predecessors, lorlatinib was initially approved for second- and third-line use in patients already treated sequentially with crizotinib and one of the second-generation drugs, or starting their treatment with a second-generation TCT. After the publication of the results of the randomized comparative study CROWN, which demonstrated a convincing advantage of the drug compared to crizotinib in the first line of treatment, its high intracranial activity, the indications were expanded. Currently, lorlatinib is registered in the Russian Federation for use in ALK-positive patients with advanced non-small cell lung cancer (NSCLC), both those who have already received targeted therapy for first and/or second generation ALK TKIs, and in untreated patients.

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Lorlatinib in Crisotinib-Resistant Alk+ NSCLC Patients. Our Result

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Efficacy of lorlatinib in the treatment of ALK-positive non-small cell lung cancer patients with progression on crizotinib: personal experience

Efficacy of lorlatinib in the treatment of ALK-positive non-small cell lung cancer patients with progression on crizotinib: personal experience

Lorlatinib: new therapeutic options for ALK-positive patients

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