Abstract
The use of lorlatinib, an anaplastic lymphoma kinase (ALK) inhibitor for the treatment of ALK-positive metastatic non-small cell lung cancer, is associated with dyslipidemia in over 80% of patients. Clinical trial protocols for the management of lorlatinib-associated dyslipidemia differ from clinical practice guidelines for the management of dyslipidemia to prevent cardiovascular disease, in that they are based on total cholesterol and triglyceride levels rather than on the low-density lipoprotein cholesterol and non-high-density lipoprotein cholesterol levels that form the basis of current cardiovascular guideline recommendations. In order to simplify and harmonize the management of cardiovascular risk in patients with lorlatinib, an advisory committee consisting of a medical oncologist, a cardiologist, and two pharmacists with expertise in cardiology and oncology aimed to develop a simplified algorithm, adapted from the Canadian Cardiovascular Society dyslipidemia recommendations. Recommendations for the evaluation and management of hypercholesterolemia and isolated hypertriglyceridemia in patients treated with lorlatinib are outlined. These recommendations are based on data collected in a large number of lipid-lowering therapy trials applicable to individuals with and without cancer. Considering the relatively long life expectancy and improving prognosis of patients with ALK translocations, this specific patient population should be treated as are patients without cancer and are likely to derive the same benefits from lipid-lowering therapy.
Highlights
For the approximately 0.5–3% of patients with non-small cell lung cancer (NSCLC) with rearrangements of the anaplastic lymphoma kinase (ALK) gene in Canada, standard therapy consists of a first- or second-generation ALK tyrosine kinase inhibitor (TKI), such as alectinib, brigatinib, crizotinib, or ceritinib [1]
Lorlatinib is indicated for the treatment of ALK-positive metastatic NSCLC in patients who have progressed on first- and/or second-generation ALK inhibitors [4]
Risk evaluation of these patients is relevant given the lorlatinib-associated hyperlipidemia and the relatively long life expectancy of NSCLC patients treated with ALK inhibitors
Summary
For the approximately 0.5–3% of patients with non-small cell lung cancer (NSCLC) with rearrangements of the anaplastic lymphoma kinase (ALK) gene in Canada, standard therapy consists of a first- or second-generation ALK tyrosine kinase inhibitor (TKI), such as alectinib, brigatinib, crizotinib, or ceritinib [1]. Lorlatinib is indicated for the treatment of ALK-positive metastatic NSCLC in patients who have progressed on first- and/or second-generation ALK inhibitors [4]. The most common treatment-related adverse events were hypercholesterolemia and hypertriglyceridemia, which occurred in 81% and 60% of patients, respectively. Despite the high prevalence of hypercholesterolemia and hyperlipidemias, these adverse events did not result in any treatment discontinuations and infrequently led to delayed or reduced doses of lorlatinib, with 3.4% and 4.7% of patients having delayed doses and 0.7% having reduced doses
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