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Patients with ALK-positive non-small-cell lung cancer who received Lorbrena reported better quality of life and had longer progression-free survival than patients who received Xalkori.
Treatment with Lorbrena (lorlatinib) demonstrated longer progression-free survival and a higher frequency of intracranial response than Xalkori (crizotinib), for those with anaplastic lymphoma kinase (ALK)-positive non-small-cell lung cancer (NSCLC), according to study results published in The New England Journal of Medicine. The drug also led to a higher increase in quality of life.
Lorbrena demonstrates antitumor activity in previously treated patients with ALK-positive NSCLC, but the drug’s efficacy compared to Xalkori is unclear, according to the authors.
They noted that a previous study once demonstrated that Xalkori was superior to platinum-based Alimta (pemetrexed) chemotherapy, which established it as a standard of care treatment in the firstline setting of ALK-positive NSCLC. But since that study, more data has become available that has demonstrated that second-generation drugs including Alecensa (alectinib), Alunbrig (brigatinib) and ensartinib were superior to Xalkori in the firstline setting. However, as the authors noted, the second-generation ALK inhibitors have their share of concerns.
“Despite the improved efficacy of second-generation inhibitors, drug resistance and recurrent disease — including central nervous system (CNS) progression, a major cause of illness and death — still develop,” they wrote.
As a result, the authors aimed to evaluate the efficacy of a third-generation inhibitor (Lorbrena) in the firstline setting of ALK-positive NSCLC, compared to Xalkori.
The study consisted of 296 patients with ALK-positive NSCLC :149 of which were randomized to Lorbrena at 100 mg daily and 147 were randomized to Xalkori at 250 mg twice daily.
Results showed that at 12 months, 78% of patients receiving Lorbrena were alive without disease progression, and 39% or patients receiving Xalkori were alive without disease progression.
A total of 76% of patients who received Lorbrena and 58% of those who received Xalkori had an objective response, meaning there was a decrease in tumor size. Among those who had measurable brain metastases 82% and 23%, respectively, had an intracranial response to therapy. Overall, 71% of patients who received Lorbrena had an intracranial response.
“Patient-reported outcomes also supported the safety and favorable side effect profile of (Lorbrena) relative to (Xalkori), and patients who received Lorbrena reported a significantly greater improvement in global quality of life than those who received Xalkori,” the study authors wrote.
The most common side effects seen in patients being treated with Lorbrena were high levels of fat particles in the blood, weight gain, pain, numbness or weakness in hands and feet (known as peripheral neuropathy) and cognitive effects. Lorbrena had more grade 3 or 4 side effects than Xalkori, and researchers relate that to the fluctuating lipid levels. Due to side effects, 7% of patients receiving Lorbrena and 9% of patients receiving Xalkori stopped treatment.
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