Bruno Strigini, CEO
The European Union (EU) has approved the use of ceritinib (Zykadia) for the first-line treatment of patients with ALK
-positive advanced non–small cell lung cancer (NSCLC).
Novartis, the manufacturer of the selective ALK-inhibitor, announced the approval in a press release. Ceritinib will be available for patients in all 28 EU member states plus Iceland, Lichtenstein, and Norway.
The approval is based on data from the open-label phase III ASCEND-4 trial, in which ceritinib was associated with a 45% reduced risk for death compared with chemotherapy (HR, 0.55; 95% CI, 0.42-0.73; P
<.0001). The median progression-free survival (PFS) benefit favoring ceritinib was 8.5 months.
The EU’s Committee for Medicinal Products for Human Use (CHMP) issued a positive opinion regarding first-line ceritinib in May. The FDA approved the drug for use in this patient population the same month.
“Today’s [European Commission] approval of Zykadia as a first-line treatment of ALK
-positive non–small cell lung cancer is an important step forward for patients with this type of serious disease,” Novartis Oncology CEO Bruno Strigini said in a press release. “Our commitment to innovation in lung cancer will continue and we look forward to providing additional advancements for patients as the incidence of the disease grows around the world.”
In ASCEND-4, treatment-naïve patients with stage IIIB or IV ALK
-positive NSCLC were randomly assigned to 750 mg daily of oral ceritinib (n = 189) or standard chemotherapy with 500 mg/m2
of pemetrexed plus 75 mg/m2
of cisplatin or carboplatin AUC 5-6, followed by pemetrexed maintenance (n = 187). Patients were enrolled at 203 locations cross 31 countries. The median treatment exposure was 66.4 weeks for ceritinib and 26.9 weeks for chemotherapy.
Beyond reaching the study’s primary endpoint of PFS, ceritinib also improved key secondary outcome measures, including objective response rate (ORR) and duration of response. Median PFS by RECIST v1.1 criteria was 16.6 months (95% CI, 12.6-27.2) compared with 8.1 months (95% CI, 5.8-11.1) with chemotherapy.
The ORR with ceritinib was higher at 72.5% compared with 26.7% in the chemotherapy group. The median duration of response was 23.9 months versus 11.1 months, respectively.
Among patients without brain metastases at screening, the median PFS was 26.3 months (95% CI, 15.4-27.7) with ceritinib versus 8.3 months (95% CI, 6.0-13.7) with chemotherapy (HR, 0.48; 95% CI, 0.33-0.69). In patients with brain metastases, the median PFS was 10.7 months (95% CI, 8.1-16.4) versus 6.7 months (95% CI, 4.1-10.6), respectively (HR, 0.70; 95% CI, 0.44-1.12).
Crossover from chemotherapy to ceritinib was allowed at disease progression; 80 patients crossed over, which could possibly impact overall survival (OS). OS data were immature at the interim analysis.
The most frequently reported all-grade adverse events (AEs) included diarrhea (85% with ceritinib vs 11% with chemotherapy), nausea (69% vs 55%), vomiting (66% vs 36%), ALT increase (60% vs 22%), AST increase (53% vs 19%), gamma-glutamyltransferase increase (37% vs 10%), decreased appetite (34% vs 31%), blood alkaline phosphate increase (29% vs 5%), and fatigue (29% vs 30%).
Ceritinib was already approved in the EU for the treatment of patients with ALK
-positive advanced NSCLC previously treated with crizotinib (Xalkori). In the United States, ceritinib was approved by the FDA in April 2014 for use in the same second-line setting.
de Castro G, Tan DS, Crinò L, et al. First-line Ceritinib Versus Chemotherapy in Patients With ALK-rearranged (ALK+) NSCLC: A Randomized, Phase 3 Study (ASCEND-4). Presented at: Presented at: 17th World Lung Cancer Conference, the Annual Meeting of the International Association for the Study of Lung Cancer (IASLC); December 4-7, 2016; Vienna, Austria.