Zykadia Shows Promise as First-Line Lung Cancer Therapy

Novartis recently announced positive results that suggest ceritinib (Zykadia) could potentially be used as a first-line treatment in patients with anaplastic lymphoma kinase-positive (ALK+) advanced non-small cell lung cancer (NSCLC).

In the phase 3 ASCEND-4 clinical trial, investigators found that patients with ALK+ NSCLC had a median progression-free survival (PFS) of 16.6 months, compared with 8.1 months in patients treated with the standard first-line treatment of chemotherapy, according to a press release from Novartis.

The 45% reduction in risk of disease progression, suggests that ceritinib could potentially be used as a first-line treatment. Results from the trial were presented at the 17th World Conference on Lung Cancer.

"These data demonstrate the potential to more than double a patient's progression-free survival when they take Zykadia as their first ALK inhibitor rather than undergoing treatment with chemotherapy," said lead investigator Gilberto de Castro Jr, MD, PhD, head of Thoracic Oncology and Head and Neck Cancer clinic in the Clinical Oncology Service of the Institute of Cancer of São Paulo. "For clinicians, who are constantly working to extend a patient's response to treatment in the first-line setting, the ASCEND-4 results are very compelling."

Data regarding the main secondary endpoint of the trial, OS, are still immature, but positive findings regarding ceritinib have been observed, Novartis reported. Other secondary endpoints include overall response rate (ORR), overall intracranial response rate (OIRR), disease control rate, and duration of response.

Patients taking ceritinib had an ORR of 72.5% compared with a response rate of only 26.7% in patients receiving chemotherapy. Patients with brain metastases taking ceritinib had an OIRR of 72.7% compared with 27.3% in patients treated with chemotherapy.

Investigators also found that patients without initial brain metastases achieved 26.3 months PFS compared with 8.3 months for patients receiving chemotherapy. Patients taking ceritinib also had a disease control rate of 84.7%, and a duration of response of 23.9 months.

Novartis reported that patients taking ceritinib were more likely to experience better health status and improvement in lung cancer symptoms compared with patients receiving chemotherapy.

The safety profile of ceritinib was consistent, and no new safety events were seen. Common adverse events included diarrhea, nausea, vomiting, ALT increase, and AST increase. These events were managed with dose adjustments or concomitant treatment, according to the press release.

At the annual meeting, Novartis also presented data from a phase 1 trial studying the pharmacokinetic profile of ceritinib 450 mg when taken with a low-fat meal versus ceritinib 750 mg after fasting, which are the drug’s current indications.

Preliminary data suggests that adverse events were comparable between both groups, but the incidences of gastrointestinal-related adverse events were lowest in patients taking ceritinib 450 mg who ate a low-fat meal.

Ceritinib is currently approved in the European Union for patients with ALK-positive NSCLC who received prior treatment with crizotinib. In the United States, ceritinib received accelerated approval for patients with ALK-positive NSCLC who progressed on, or are intolerant to crizotinib, according to Novartis.

"The patient response to treatment is high and durable in the first-line setting," said Bruno Strigini, CEO, Novartis Oncology. "Based on these results, Novartis is initiating discussions with regulatory authorities worldwide regarding this potential use of Zykadia to further improve outcomes for patients with ALK+ advanced NSCLC."