As reported in JAMA Oncology by Leora Horn, MD, MSc, FRCPC, and colleagues, the phase III eXalt3 trial has shown significantly prolonged progression-free survival with ensartinib vs crizotinib in patients with advanced, recurrent, or metastatic anaplastic lymphoma kinase (ALK)-positive non–small cell lung cancer (NSCLC) with no prior ALK inhibitor treatment.
Leora Horn, MD, MSc, FRCPC
In the open-label trial, 290 patients with ALK-positive disease (intent-to-treat population) from sites in 21 countries were randomly assigned between July 2016 and November 2018 to receive ensartinib at 225 mg once daily (n = 143) or crizotinib at 250 mg twice daily (n = 147) until disease progression or unacceptable toxicity. Enrollment of patients with asymptomatic brain metastases was permitted. Patients may have received up to one prior chemotherapy regimen for metastatic disease. A modified intent-to-treat population consisted of 121 patients treated with ensartinib and 126 patients treated with crizotinib with central laboratory–confirmed ALK-positive disease. The primary endpoint was progression-free survival on blinded independent review committee assessment.
Median follow-up was 23.8 months (range = 0–44 months) in the ensartinib group and 20.2 months (range = 0–38 months) in the crizotinib group. In the intent-to-treat population, median progression-free survival was 25.8 months (95% confidence interval [CI] = 21.8 months–not reached) in the ensartinib group vs 12.7 months (95% CI = 9.2–16.6 months) in the crizotinib group (hazard ratio [HR] = 0.51, 95% confidence interval [CI] = 0.35–0.72, P < .001). In the modified intent-to-treat population, median progression-free survival was not reached (95% CI = 20.2 months–not reached) in the ensartinib group vs 12.7 months (95% CI = 8.9–16.6 months) in the crizotinib group (HR = 0.45, 95% CI = 0.30–0.66, P < .001).
Among patients with measurable brain metastases in the modified intent-to-treat population, intracranial response was observed in 7 (63.6%) of 11 ensartinib patients vs 4 (21.1%) of 19 crizotinib patients. Median progression-free survival among patients without brain metastases was not reached with ensartinib vs 16.6 months with crizotinib (HR = 0.46, 95% CI = 0.27–0.77, P = .003), reflecting a reduced rate of central nervous system disease progression in the ensartinib group (4.2% vs 23.9% at 12 months; cause-specific HR = 0.32, 95% CI = 0.16–0.63, P = .001).
In the modified intent-to-treat population, at time of analysis, death had occurred in 30 patients (24.8%) in the ensartinib group vs 32 patients (25.4%) in the crizotinib group (HR = 0.91, 95% CI = 0.54–1.54); 2-year overall survival rates were 78% (95% CI = 69%–84%) vs 78% (95% CI = 70%–85%).
In the intent-to-treat population, the most common ensartinib-related adverse events of any grade (primarily grade 1 or 2) were rash (67.8%), elevated alanine aminotransferase (48.3%) and aspartate aminotransferase (37.8%), and pruritus (26.6%). The most common ensartinib-related grade 3 adverse event was rash (11.2%); three grade 4 treatment-related adverse events were reported, consisting of increased bilirubin, increased creatine phosphokinase, and hyponatremia. Treatment-related serious adverse events occurred in 7.7% of patients in the ensartinib group vs 6.1% of the crizotinib group. Treatment-related adverse events led to discontinuation in 9.1% vs 6.8% of patients. No treatment-related deaths occurred in either group.
The investigators concluded, “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.”
Leora Horn, MD, MS, of Vanderbilt-Ingram Cancer Center, and Yi-Long Wu, MD, of Guangdong Provincial People’s Hospital and Guangdong Academy of Medical Sciences, Guangzhou, are the corresponding authors for the JAMA Oncology article.
Disclosure: The study was funded by Xcovery Holdings Inc. For full disclosures of the study authors, visit jamanetwork.com.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.