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Ensartinib bests crizotinib in ALK-positive non-small cell lung cancer

JAMA Oncology
Reuters Health - 10/09/2021 - Ensartinib, an oral tyrosine kinase inhibitor of anaplastic lymphoma kinase (ALK), was superior to crizotinib in a phase 3 multicenter trial of patients with ALK-positive non-small cell lung cancer (NSCLC).

Dr. Leora Horn of AstraZeneca, who was on the faculty of Vanderbilt University in Nashville at the time of the study, told Reuters Health by email, "The positive results from the trial would indicate ensartinib is preferred over crizotinib in patients with ALK-positive NSCLC."

"The efficacy of ensartinib is superior to crizotinib in all subsets of patients, including in those with CNS disease at baseline," she said. "The data also indicate that ensartinib was well tolerated."

Vanderbilt researchers took the drug from a first-in-human to a global phase 3 study, she noted. "I am personally excited to see the results of this study and once approved, ensartinib will present another first-line option for (these) patients."

As reported in JAMA Oncology, the open-label, randomized, phase 3 trial was conducted in 120 centers in 21 countries. Two hundred and ninety patients with advanced, recurrent or metastatic ALK-positive NSCLC (median age, 54; 51% men) were randomized to ensartinib, 225 mg once daily, or crizotinib, 250 mg twice daily.

The primary end point was progression-free survival (PFS) as assessed by a blinded independent review committee. Secondary end points included systemic and intracranial response, time to central nervous system (CNS) progression, and overall survival.

Efficacy was assessed in the intent-to-treat (ITT) group as well as a prespecified modified ITT (mITT) group consisting of patients with confirmed ALK-positive NSCLC.

In the ITT population, the median PFS was significantly longer with ensartinib than with crizotinib (25.8 months vs. 12.7 months; hazard ratio, 0.51), over a median follow-up of 23.8 months for ensartinib and 20.2 months for crizotinib.

In the mITT population, the median PFS in the ensartinib group was not reached, and the median PFS in the crizotinib group was 12.7 months (HR).

The intracranial response rate was 63.6% with ensartinib versus 21.1% with crizotinib, for those with target brain metastases at baseline.

A lower CNS progression rate in patients without brain metastases (at 12 months: 4.2% with ensartinib vs. 23.9% with crizotinib; cause-specific HR, 0.32) led to the PFS not being reached with ensartinib versus 16.6 months with crizotinib.

Frequencies of treatment-related serious adverse events were similar between groups with no new safety signals: 11 (7.7%) with ensartinib versus 9 (6.1%) with crizotinib. Dose reductions were also similar (ensartinib, 23.8% vs. crizotinib, 19.9%), as were drug discontinuations (ensartinib, 9.1% vs. crizotinib, 6.8%).

Dr. Ibiayi Dagogo-Jack of Massachusetts General Hospital in Boston, author of a related editorial, commented by email, "We now have multiple highly efficacious next-generation ALK inhibitors with encouraging and durable activity in the first-line setting, and (this) study again confirms that next-generation ALK inhibitors, in general, should be prioritized over crizotinib for first-line treatment."

Financial support was provided by Xcovery Holdings Inc, which manufactures and intends to market ensartinib after approval by regulatory authorities. Six coauthors are affiliated with the company and Dr. Horn and several coauthors have received fees from it.

SOURCE: https://bit.ly/3jYZWRd and https://bit.ly/2VwayxE JAMA Oncology, online September 2, 2021.

By Marilynn Larkin

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