Ensartinib Improves Progression-Free Survival in Patients with ALK-Positive NSCLC

August 27, 2020

The novel next-generation ALK tyrosine kinase inhibitor improved survival, compared with Xalkori, in patients with ALK-positive non-small cell lung cancer, potentially representing a new option in the first-line setting.

Treatment with ensartinib induced longer progression-free survival, compared with Xalkori (crizotinib) in patients with anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC), according to new clinical trial data presented at International Association for the Study of Lung Cancer (IASLC) World Conference on Lung Cancer Virtual Presidential Symposium.

Dr. Leora Horn, Ingram Associate Professor of Cancer Research in the Division of Hematology/Oncology and director of the Thoracic Oncology Program at Vanderbilt-Ingram Cancer Center in Nashville noted that the novel next-generation ALK tyrosine kinase inhibitor (TKI) represents a new option in the first-line setting for these patients.

The researchers randomized 290 patients – which comprised the prespecified intent to treat (ITT) population with locally determined ALK-positive NSCLC – to evaluate the efficacy and safety of ensartinib, compared with Xalkori, which is approved for the treatment of some subtypes of patients with NSCLC, including ALK-positive patients. The modified (mITT) population – which comprised the prespecified patient population that was ALK-positive as confirmed by central Abbott FISH test – included 247 patients (121 patients in the ensartinib arm and 126 patients in the Xalkori arm).

Median age of the study participants was 54.1 years. Overall, 26% of patients received chemotherapy prior to the study and 36% of patients had brain metastases as baseline, which included 5% of those patients having prior brain radiotherapy.

As of the July 1, 2020 data cutoff, treatment was ongoing in 64 patients (45%) being treated with ensartinib and 25 (17%) of those in the Xalkori arm.Median follow-up was 23.8 and 20.2 months, respectively, in the ensartinib and Xalkori arms.

In total, 139 patients experienced disease progression or death, including 73% in the ITT population and 63% in the mITT population.

Median progression-free survival – or the time from treatment to disease worsening – was 25.8 months in the ensartinib arm, compared with 12.7 months with Xalkori, leading to a 48% reduction in the risk for disease progression following treatment. Horn noted this analysis showed a statistically significant difference in progression-free survival between the two groups.

In the mITT population, median progression-free survival has not been reached yet for those receiving ensartinib, compared with 12.7 months for the Xalkori arm – resulting in a 52% reduced risk for disease progression.

The overall response rates – or the proportion of patients who have a partial or complete response to therapy – were 75% and 67%, respectively, in the ensartinib and Xalkori arms. In particular, among patients with measurable brain metastases, the intracranial overall response rate was 64% with ensartinib, compared with 21% with Xalkori. Moreover, time-to-treatment-failure rate in patients with no baseline brain metastases was also significantly lower with ensartinib at 12 months, compared with Xalkori (4% versus 24%).


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