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Clin Cancer Res. 2016 Nov 1;22(21):5171-5176. Epub 2016 Jul 13.

FDA Approval: Alectinib for the Treatment of Metastatic, ALK-Positive Non-Small Cell Lung Cancer Following Crizotinib.

Author information

1
Office of Hematology and Oncology Products, U.S. Food and Drug Administration, Silver Spring, Maryland. erin.larkins@fda.hhs.gov.
2
Office of Hematology and Oncology Products, U.S. Food and Drug Administration, Silver Spring, Maryland.
3
Office of Biostatistics, U.S. Food and Drug Administration, Silver Spring, Maryland.
4
Office of Pharmaceutical Quality, U.S. Food and Drug Administration, Silver Spring, Maryland.
5
Office of Translational Sciences, U.S. Food and Drug Administration, Silver Spring, Maryland.

Abstract

On December 11, 2015, the FDA granted accelerated approval to alectinib (Alecensa; Genentech) for the treatment of patients with anaplastic lymphoma receptor tyrosine kinase (ALK)-positive, metastatic non-small cell lung cancer (NSCLC) who have progressed on or are intolerant to crizotinib. This approval was based on two single-arm trials including 225 patients treated with alectinib 600 mg orally twice daily. The objective response rates (ORR) by an independent review committee in these studies were 38% [95% confidence interval (CI), 28-49] and 44% (95% CI, 36-53); the median durations of response (DOR) were 7.5 months and 11.2 months. In a pooled analysis of 51 patients with measurable disease in the central nervous system (CNS) at baseline, the CNS ORR was 61% (95% CI, 46-74); the CNS DOR was 9.1 months. The primary safety analysis population included 253 patients. The most common adverse reactions were fatigue (41%), constipation (34%), edema (30%), and myalgia (29%). The most common laboratory abnormalities were anemia (56%), increased aspartate aminotransferase (51%), increased alkaline phosphatase (47%), increased creatine phosphokinase (43%), hyperbilirubinemia (39%), hyperglycemia (36%), increased alanine aminotransferase (34%), and hypocalcemia (32%). Dose reductions due to adverse reactions occurred in 12% of patients, whereas 27% of patients had alectinib dosing interrupted for adverse reactions. Permanent discontinuation of alectinib due to adverse reactions occurred in only 6% of patients. With the clinically meaningful ORR and DOR as well as the safety profile observed in these trials, alectinib was determined to have a favorable benefit-risk profile for the treatment of the indicated population. Clin Cancer Res; 22(21); 5171-6.

PMID:
27413075
DOI:
10.1158/1078-0432.CCR-16-1293
[Indexed for MEDLINE]
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