Ceritinib vs Chemotherapy in Previously Treated ALK-Rearranged NSCLC

Key Points

  • In patients with advanced ALK-rearranged NSCLC, ceritinib significantly improved progression-free survival vs chemotherapy.
  • Objective response was observed in 39% vs 7%.

The phase III ASCEND-5 trial has shown a significant improvement in progression-free survival with ceritinib (Zykadia) vs chemotherapy in advanced ALK-rearranged non–small cell lung cancer (NSCLC) previously treated with crizotinib (Xalkori) and chemotherapy. Trial results were reported in The Lancet Oncology by Shaw et al.

Study Details

In the open-label trial, 231 patients from 99 sites in 20 countries were randomized between June 2013 and November 2015 to receive ceritinib at 750 mg/d (n = 115) or chemotherapy (n = 116) consisting of investigator choice of pemetrexed (Alimta) at 500 mg/m² (n = 40) or docetaxel at 75 mg/m² (n = 73) every 21 days (3 patients withdrew before receiving study treatment). In addition to crizotinib, patients had received one or two lines of chemotherapy including a platinum doublet. Patients who discontinued chemotherapy because of progressive disease could cross over to the ceritinib group. The primary endpoint was progression-free survival assessed by a masked independent review committee in the intention-to-treat population.

Progression-Free Survival

Median follow-up was 16.5 months. Median progression-free survival was 5.4 months in the ceritinib group vs 1.6 months in the chemotherapy group (hazard ratio [HR] = 0.49, P < .0001). In a post hoc analysis, median progression-free survival was 2.9 months in chemotherapy patients receiving pemetrexed (HR = 0.73, 95% confidence interval [CI] = 0.47–1.13) and 1.5 months in those receiving docetaxel (HR = 0.32, 95% CI = 0.22–0.47). The progression-free survival benefit for ceritinib was consistent across subgroups according to age, sex, race, smoking history, World Health Organization performance status, presence of brain metastases, previous response to crizotinib, and disease burden.

Objective response occurred in 39% vs 7% of patients, with median response durations of 6.9 vs 8.3 months. Among patients with active target brain lesions, response was observed in 6 of 17 receiving ceritinib and 1 of 20 receiving chemotherapy.

Adverse Events

The most common grade 3 or 4 adverse events in the ceritinib group were increased alanine transaminase (21% vs 2% in chemotherapy group), increased gamma-glutamyltransferase (21% vs 1%), and increased aspartate transaminase (14% vs 1%). Serious adverse events occurred in 43% vs 32% of patients. Adverse events led to treatment discontinuation in 5% vs 6%.

The investigators concluded: “These findings show that patients derive significant clinical benefit from a more potent ALK inhibitor after failure of crizotinib and establish ceritinib as a more efficacious treatment option compared with chemotherapy in this patient population.”

The study was funded by Novartis Pharmaceuticals Corporation.

Alice T. Shaw, MD, of Massachusetts General Hospital, is the corresponding author of The Lancet Oncology article.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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