Treatment with ceritinib significantly improved progression-free survival compared with chemotherapy in treatment-naïve patients with advanced anaplastic lymphoma kinase (ALK)-rearranged non-small cell lung cancer (NSCLC), a study published in the journal The Lancet has shown.1
Ceritinib is a kinase inhibitor indicated for the treatment of patients with ALK-positive metastatic NSCLC who have progressed on or are intolerant to crizotinib; however, the efficacy of ceritinib in patients with untreated ALK-rearranged NSCLC is unknown.
To assess the efficacy and safety of ceritinib compared with platinum-based chemotherapy in this population, researchers enrolled 376 untreated patients stage IIIB/IV ALK-rearranged non-squamous NSCLC from 28 countries.
For the open-label, phase 3 ASCEND-4 study (ClinicalTrials.gov Identifier: NCT01828099), investigators randomly assigned patients 1:1 to receive ceritinib orally daily or pemetrexed plus cisplatin or carboplatin every 3 weeks for 4 cycles followed by maintenance pemetrexed.
Results showed that treatment with ceritinib significantly reduced the risk of progression or death by 45% compared with platinum-based chemotherapy (hazard ratio, 0.55; 95% CI, 0.42-0.73; P <.00001). Median progression-free survival was 16.6 months (95% CI, 12.6-27.2) and 8.1 months (95% CI, 5.8-11.1) with ceritinib and chemotherapy, respectively.
Investigators observed a progression-free survival benefit for both patients with brain metastases at the time of study entry and those without brain metastases.
Researchers also found that the most common adverse events in the ceritinib arm were diarrhea (85%), nausea (69%), vomiting (66%), and increased alanine aminotransferase (60%).
The study further demonstrated that ceritinib significantly improved quality of life and significantly prolonged time to deterioration for lung cancer-specific symptoms compared with chemotherapy.
The findings ultimately suggest that ceritinib could be considered a novel frontline therapeutic option in patients with ALK-rearranged NSCLC.
1. Soria JC, Tan DS, Chiari R, et al. First-line ceritinib versus platinum-based chemotherapy in advanced ALK-rearranged non-small-cell lung cancer (ASCEND-4): a randomised, open-label, phase 3 study. Lancet. 2017 Jan 23. doi: 10.1016/S0140-6736(17)30123-X. [Epub ahead of print]