Ceritinib Approved by the FDA for Frontline ALK+ NSCLC


Ceritinib (Zykadia) has been approved by the FDA for the treatment of patients with <em>ALK</em>-positive, metastatic non&ndash;small cell lung cancer.

Ceritinib (Zykadia) has been approved by the FDA for the treatment of patients withALK-positive, metastatic non—small cell lung cancer (NSCLC), according to Novartis, the manufacturer of the second-generation ALK inhibitor.

Patients&rsquo;ALK-positive status must be determined by an FDA-approved test.

The approval is based on findings from the phase III ASCEND-4 trial, in which ceritinib reduced the risk of disease progression or death by 45% compared with standard chemotherapy. The median progression-free survival (PFS) benefit favoring ceritinib was 8.5 months (HR, 0.55; 95% CI, 0.42-0.73;P<.0001).

&ldquo;Today&rsquo;s approval represents the next step in the development of Zykadia as a treatment option forALK-positive metastatic NSCLC, bringing this important medication to a patient population where a need still exists,&rdquo; said Bruno Strigini, CEO, Novartis Oncology. &ldquo;At Novartis, we are tireless in our pursuit of developing novel medicines to treat lung cancer, and the first-line approval of Zykadia forALK-positive metastatic NSCLC illustrates our commitment to cancer patients.&rdquo;

The open-label phase III ASCEND-4 trial randomized 376 treatment-na&iuml;ve patients with stage IIIB or IV ALK+ NSCLC to either 750 mg of oral ceritinib daily or standard chemotherapy (500 mg/m2of pemetrexed plus 75 mg/m2of cisplatin or carboplatin AUC 5-6), including pemetrexed maintenance. 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&rsquo;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 (67% vs 36%), ALT increase (91% vs 65%), AST increase (86% vs 58%), gamma-glutamyltransferase increase (84% vs 67%), decreased appetite (34% vs 32%), blood alkaline phosphate increase (81% vs 47%), and fatigue (45% vs 49%).

In the United States, ceritinib was approved by the FDA in April 2014 for the treatment of patients withALK-positive advanced NSCLC previously treated with crizotinib (Xalkori).


de Castro G, Tan DS, Crin&ograve; 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.

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