This week's issue of the New England Journal of Medicine includes a study of Novartis' (NVS) ALK-inhibitor ceritinib demonstrating strong activity in ALK-positive non-small cell lung cancer, including patients previously treated with Pfizer's (PFE) Xalkori, another ALK-inhibitor. An editorial supportive of ceritinib accompanies the study publication in the same NEJM issue.
Novartis has already submitted ceritinib (also known as LDK378) to the FDA for approval, although the company has not disclosed an approval decision date. Approximately 5% of lung cancers involve tumors with alternations to the ALK gene.
Ariad Pharmaceuticals (ARIA) is developing its own ALK inhibitor AP26113 in lung cancer, but a pivotal study was just started so the company is significantly behind Novartis.
The Novartis study enrolled patients with non-small cell lung cancer which harbored genetic alterations to the ALK gene. Among 114 patients who received at least 400 mg of ceritinib per day, the overall response rate was 58%. Among a subset of patients treated with Pfizer's Xalkori previously, the response rate was 56%. The median progression-free survival was 7 months, according to the NEJM publication.
"This suggests that in patients with ALK-rearranged NSCLC, a more potent and specific ALK inhibitor can effectively treat the majority of patients in whom resistance to crizotinib develops," the ceritinib study authors conclude.
The safety profile of ceritinib was found to be similar to Xalkori, except for higher rates of diarrhea and nausea.
Here's how the NEJM editorial sums up the ceritinib data:
"The study by Shaw and colleagues is good news for patients with ALK -rearranged lung cancer. It is also an example of how mechanistically inspired and rationally designed trials involving large, genotypically defined patient cohorts can lead to dramatic steps forward in the care of patients with cancer."