Objective: To review ceritinib for the treatment of anaplastic lymphoma kinase (ALK)-positive metastatic non–small-cell lung cancer (NSCLC). Data Sources: Literature searches were conducted in PubMed, EMBASE (1974 to July week 5, 2014), and Google Scholar using the terms ceritinib, LDK378, and non–small-cell lung cancer. Study Selection and Data Extraction: One phase 1 trial and 2 abstracts were identified. Data Synthesis: Ceritinib is approved for the treatment of ALK-positive metastatic NSCLC in patients who are intolerant to or have progressed despite therapy with crizotinib. In the phase 1 clinical trial, the maximum tolerated dose was determined to be 750 mg once daily. The overall response rate (ORR) was 58% (95% CI = 48-67) in patients who received ≥400 mg daily (n = 114). In this group, the ORR was 56% (95% CI = 41-67) and 62% (95% CI = 44-78) among crizotinib-exposed and -naïve patients, respectively. The ORR was 59% (95% CI = 47-70) in patients who received 750 mg daily (n = 78). The ORR was 56% (95% CI = 41-70) in crizotinib-treated patients and 64% (95% CI = 44-81) in crizotinib-naïve patients, respectively, in this subset. The median duration of response was 8.2 months. Median progression-free survival was 7.0 months. The most common adverse reactions included diarrhea, nausea, vomiting, abdominal pain, anorexia, constipation, fatigue, and elevated transaminases. Conclusions: Ceritinib has activity in crizotinib-resistant and crizotinib-naïve patients and appears to be a viable alternative for ALK-positive NSCLC. Long-term data are needed to further define the role of ceritinib in the treatment of NSCLC.
American Cancer Society. Cancer Facts and Figures 2014. Atlanta, GA: American Cancer Society; 2014.
2.
KwakELBangYJCamidgeDR. Anaplastic lymphoma kinase inhibition in non–small-cell lung cancer. N Engl J Med. 2010;363:1693-1703. doi:10.1056/NEJMoa100-6448.
3.
MarsiljeTHPeiWChenB. Synthesis, structure-activity relationships, and in vivo efficacy of the novel potent and selective anaplastic lymphoma kinase (ALK) inhibitor 5-chloro-N2-(2-isopropoxy-5-methyl-4-(piperidin-4-yl)phenyl)-N4-(2-(isopropylsulfonyl)phenyl)pyrimidine-2,4-diamine (LDK378) currently in phase 1 and phase 2 clinical trials. J Med Chem. 2013;56:5675-5690. doi:10.1021/jm400-402q.
4.
ShawATKimDWMehraR. Ceritinib in ALK-rearranged non-small-cell lung cancer. N Engl J Med. 2014;370:1189-97. doi:10.1056/NEJMoa1311107.
ShawATKimDWNakagawaK. Crizotinib versus chemotherapy in advanced ALK-positive lung cancer. N Engl J Med. 2013;368:2385-2394. doi:10.1056/NEJMoa1214886.
7.
KatayamaRShawATKhanTM. Mechanisms of acquired crizotinib resistance in ALK-rearranged lung cancers. Sci Transl Med. 2012;4(120):1-25. doi:10.1126/scitranslmed.3003316.
8.
FribouletLLiNKatayamaR. The ALK inhibitor ceritinib overcomes crizotinib resistance in non-small cell lung cancer. Cancer Discov. 2014;4(12):1-12. doi:10.1158/2159-8290.CD-13-0846.
SalgiaR. Role of c-met in cancer: emphasis on lung cancer. Semin Oncol. 2009;36(2, suppl 1):S52-S58. doi:10.1053/j.seminoncol.2009.02.008.
12.
KimDWMehraRTanDSW. Ceritinib in advanced anaplastic lymphoma kinase (ALK-rearranged (ALK+) non-small cell lung cancer (NSCLC): results of the ASCEND-1 trial. J Clin Oncol. 2014;32(15, suppl 1):8003.
13.
TanDSWShawATMehraR. Ceritinib in Asian versus Caucasian patients with advanced anaplastic lymphoma kinase (ALK)-rearranged (ALK+) NSCLC: subgroup analysis of the ASCEND-1 trial. J Clin Oncol. 2014;32(15, suppl 1):8078.
