First-line ceritinib achieved statistically significant and clinically meaningful improvement in median progression-free survival (PFS) with an estimated 45% risk reduction for patients with advanced ALK-positive non-small cell lung cancer (NSCLC) compared with chemotherapy including maintenance, according to results presented at the International Association for the Study of Lung Cancer (IASLC) 17th Annual World Conference on Lung Cancer (WCLC) in Austria.1
The authors presented results of the ASCEND-4 phase 3 trial, in which ceritinib also achieved high and durable systemic responses and high overall intracranial response rate (OIRR) in patients with measurable brain metastases.
Patients with untreated ALK-positive, advanced non-squamous NSCLC were randomly assigned (1:1) to receive either 750 mg per day of ceritinib (189 patients, 59 of whom had brain metastases) or chemotherapy (187 patients, 62 of whom had brain metastases). Patients were stratified by performance status (0 or 1-2), presence or absence of brain metastases at screening, and prior neo or adjuvant chemotherapy.
Crossover from chemotherapy to ceritinib was allowed at progression, and 80 patients crossed over. Median treatment exposure was 66.4 weeks for ceritinib and 26.9 weeks for chemotherapy.
Ceritinib demonstrated statistically significant improvement in PFS; patients in the ceritinib arm had a median PFS of 16.6 months, compared to 8.1 months in the chemotherapy arm. OS in the ceritinib arm was 23.9 months in the ceritinib arm and 11.1 months in the chemotherapy arm. Overall response rate was also higher in the ceritinib arm, at 72.5%, than the chemotherapy arm, at 26.7%. IORR was 72.7% versus 27.3%, respectively.
The most common adverse events in patients treated with ceritinib were diarrhea (84.7%), nausea (68.8%), vomiting (66.1%), alanine aminotransferase increase (60.3%), and aspartate aminotransferase increase (52.9%).
- De Castro Jr G, Tan DS, Crinò L, et al. BRAIN: First-line ceritinib versus chemotherapy in patients with ALK-rearranged (ALK+) NSCLC: A randomized, phase 3 study (ASCEND-4). Paper presented at: the International Association for the Study of Lung Cancer 17th World Conference on Lung Cancer; December 2016; Vienna, Austria.