Adjuvant treatment with the first-generation ALK inhibitor crizotinib failed to improve disease-free survival outcomes over observation for patients with surgically resected ALK-positive non–small cell lung cancer (NSCLC), according to findings from the phase III E4512 trial presented at the International Association for the Study of Lung Cancer 2025 World Conference on Lung Cancer (Abstract PL02.18).
“Adjuvant crizotinib does not prolong disease-free survival in resected ALK+ NSCLC,” stated presenting study author David Gerber, MD, a medical oncologist at UT Southwestern Harold C. Simmons Comprehensive Cancer Center.
More on E4512
Patients eligible for enrollment in the E4512 study were identified through the ALCHEMIST screening trial. All eligible patients had resected stage IIA–IIIB disease; negative margins from surgery; a performance status of 0 or 1; and ALK positivity on fluorescence in situ hybridization, immunohistochemistry, or next-generation sequencing.
Participating patients were not allowed to have received prior treatment with an ALK inhibitor, but prior adjuvant chemotherapy and postoperative radiation therapy were allowed.
In the study, patients were randomized to either an observation arm or an investigational arm where they received crizotinib at 250 mg twice daily for up to 2 years.
The investigators had planned to enroll 168 patients in the study, but enrollment was concluded after 166 patients were enrolled when the FDA approved adjuvant alectinib for the treatment of patients with resected ALK-positive NSCLC.
Key Study Findings
After a median follow-up of 58.3 months, the median disease-free survival was 72.8 months in the crizotinib arm and 75.1 months in the observation arm (hazard ratio [HR] = 1.06; 95% confidence interval [CI] = 0.63–1.77; P = .86).
The median overall survival, a secondary endpoint, was not reached in either arm (HR = 0.49; 95% CI = 0.18–1.37; P = .26).
In the crizotinib arm, grade 3 treatment-related adverse events were reported in 34% of patients; the most common side effects were diarrhea (6%) and edema (4%). One grade 4 treatment-related event, a stroke, was reported. Twenty-two percent of patients required dose reductions and 25% discontinued treatment due to toxicities.
The median duration of treatment with crizotinib was 13.6 months (interquartile range = 3.4–23.9 months).
Disclosure: For full disclosures of the study authors, visit abstractsonline.com.
