Non-Small Cell Lung Cancer Coverage from Every Angle

How Does Ensartinib Compare With Crizotinib in First-Line Treatment of ALK-Positive NSCLC?

By: Justine Landin, PhD
Posted: Monday, November 22, 2021

Patients with ALK-positive non–small cell lung cancer (NSCLC) may have improved outcomes following first-line treatment with the next-generation ALK tyrosine kinase inhibitor (TKI) ensartinib compared with the first-generation TKI crizotinib, according to results from the phase III eXalt3 trial. In fact, according to Leora Horn, MD, MS, of Vanderbilt-Ingram Cancer Center, Nashville, and colleagues, ensartinib treatment doubled the progression-free survival and tripled the intracranial response rate compared with crizotinib treatment. The findings of this international, open-label, randomized study were published in JAMA Oncology.

“The eXalt3 study provides further confirmation that first-line treatment with next-generation ALK TKIs should be the standard of care for patients with advanced ALK-positive NSCLC,” stated Ibiayi Dagogo-Jack, MD, of Harvard Medical School, Boston, in an accompanying editorial published in JAMA Oncology.

Patients with central laboratory–confirmed advanced, recurrent, or metastatic ALK-positive NSCLC with no prior ALK TKI inhibitor treatment were enrolled. Patients were split into either intent-to-treat population (n = 290) positive for ALK or a prespecified modified intent-to-treat population (n = 247) and randomly assigned to receive either ensartinib or crizotinib.

In the intent-to-treat population, progression-free survival was found to be significantly longer with ensartinib (25.8 months) than with crizotinib (12.7 months; hazard ratio [HR] = 0.51, P < .001). In the modified intent-to-treat population, median progression-free-survival was not reached in the ensartinib group but was 12.7 months in the crizotinib group (HR = 0.45, P < .001). Patients with brain metastases at baseline treated with ensartinib had an intracranial response rate of 63.6%, compared with 21.1% with crizotinib. For those without brain metastases, the ensartinib group did not reach progression-free survival and had a central nervous system progression rate of 23.9%, compared with 16.6 months and 4.2% with ensartinib (HR = 0.32, P = .001). There appeared to be no new safety signals as well as no differences in treatment-related serious adverse events, dose reductions, or drug discontinuations across groups.

Disclosure: For full disclosures of the study authors, visit

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