Ensartinib vs Crizotinib for ALK-Positive NSCLC

Ensartinib demonstrated superior efficacy to crizotinib for patients with advanced anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC) in a study published in JAMA Oncology (2021. doi:10.1001/jamaoncol.2021.3523).

“Ensartinib, an oral tyrosine kinase inhibitor of ALK, has shown systemic and central nervous system efficacy for patients with ALK-positive NSCLC,” wrote Leora Horn, MD, MS, Division of Hematology and Oncology, Department of Medicine, Vanderbilt-Ingram Cancer Center, Nashville, Tennessee, and colleagues.

This open-label, multicenter, randomized, phase 3 trial aimed to compare ensartinib with crizotinib among patients with advanced ALK-positive NSCLC who had not received prior treatment with an ALK inhibitor.

A total of 290 patients were enrolled in the study between July 25, 2016, and November 12, 2018. Patients were randomized in a 1:1 ratio to ensartinib 225 mg once daily or crizotinib 250 mg twice daily.

The primary end point of the study was progression-free survival (PFS) as assessed by independent review committee (IRC). Secondary end points include systemic and intracranial response, time to central nervous system progression, and overall survival (OS).

Efficacy was assessed in the intent-to-treat (ITT) population and a prespecified modified ITT population consisting of patients with central laboratory-confirmed ALK-positive NSCLC.

The median PFS was significantly longer with ensartinib (25.8 months) compared to crizotinib (12.7 months) in the ITT population, with a median follow-up of 23.8 months and 20.38 months for each group, respectively. In the modified ITT population, the median PFS was not reached in the ensartinib group compared to 12.7 months in the crizotinib group.

The intracranial response rate confirmed by blinded IRC was 63.6% with ensartinib vs 21.1% with crizotinib for patients with target brain metastases at base line. For patients without brain metastases, PFS was not reached with ensartinib bs 16.6 months with crizotinib, due to a lower central nervous system progression rate (4.2% vs 23.9%, respectively, at 12 months).

There were 11 (7.7%) treatment-related serious adverse events with ensartinib vs 9 (6.1%) with crizotinib. There were 34 of 143 (23.8%) treatment-related dose reductions with ensartinib vs 29 of 146 (19.9%) with crizotinib. Lastly, there were 13 of 143 (9.1%) treatment-related drug discontinuations with ensartinib vs 10 of 146 (6.8%) with crizotinib. No new safety signals were identified.

“In this randomized clinical trial, ensartinib showed superior efficacy to crizotinib in both systemic and intracranial disease. Ensartinib represents a new first-line option for patients with ALK-positive NSCLC,” concluded Dr Horn and colleagues.—Janelle Bradley