In a study published in the March 27th issue of the New England Journal of Medicine, patients with advanced anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC) who were treated with at least 400 mg/day of ceritinib experienced an overall response rate of 58% and median progression-free survival (PFS) of 7.0 months.1

Genetic alterations of ALK contribute to the growth and development of tumors. Approximately 5% of NSCLCs are ALK-positive and are therefore sensitive to ALK inhibitors such as crizotinib. Inevitably, however, resistance develops, and most patients with ALK-positive NSCLC progress within 12 months despite treatment with crizotinib. Ceritinib is an ALK inhibitor that is 20 times more potent than crizotinib.

Majority of Patients Respond

A total of 130 patients (122 with NSCLC, 8 with other cancers) were included in the study. Among the 114 patients with NSCLC who received at least 400 mg/day of ceritinib, 1 patient (1%) had a complete response, 65 (57%) had a partial response, and 25 (22%) had stable disease. Twelve (11%) patients had early progressive disease and 11 (10%) withdrew from the study before response could be determined.

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In the 80 patients with NSCLC previously treated with crizotinib, the overall response rate was 56% and median PFS was 6.9 months. In the 34 patients with NSCLC not previously treated with crizotinib, the overall response rate was 62% and median PFS was 10.4 months.

At 12 months, the overall survival rate of patients treated with at least 400 mg/day of ceritinib was 65%.

“The majority of patients in the study experienced a clinical response to LDK378 [ceritinib],” said lead investigator Alice T. Shaw, MD, PhD, of the Massachusetts General Hospital Cancer Center, Boston, MA. “In addition, responses were seen in untreated lesions in the central nervous system in patients who previously received crizotinib. These results are important because most patients experience a disease relapse less than a year after starting crizotinib and have limited treatment options.”

Few Patients Discontinue for Adverse Events

Ceritinib therapy was generally well tolerated. Nausea occurred in 82% of patients, diarrhea in 75%, vomiting in 65%, fatigue in 47%, and increased alanine aminotransferase levels in 35%. The most common grade 3 or 4 adverse events (AEs) were increased alanine aminotransferase levels (21%), increased aspartate aminotransferase levels (11%), diarrhea (7%), and increased lipase levels (7%). AEs required discontinuation of ceritinib in eight patients.

Place in Therapy

In an accompanying editorial, Roman K. Thomas, MD, suggested that, based on this study, crizotinib and ceritinib should be given sequentially.2 “The most intuitive scenario may be second-line treatment after relapse following crizotinib treatment,” he wrote. “It is plausible that the progression-free survival of these two lines of therapy may simply be added to ultimately confer a prolongation of overall survival.”

It is tempting to consider ceritinib for front-line therapy, Dr. Thomas wrote, but before that can be recommended, head-to-head comparisons between ceritinib and crizotinib would be necessary.

The US Food and Drug Administration has designated ceritinib as a breakthrough therapy, a classification intended to expedite the development and review of drugs that treat serious or life-threatening conditions.


  1. Shaw AT, Kim D-W, Mehra R, et al. Ceritinib in ALK-rearranged non–small-cell lung cancer. N Engl J Med. 2014;370(13):1189-1197.
  2. Thomas RK. Overcoming drug resistance in ALK-rearranged lung cancer. N Engl J Med. 2014;370(13):1250-1251.