Medline ® Abstracts for References 41,51,52
of 'Anaplastic lymphoma kinase (ALK) fusion oncogene positive non-small cell lung cancer'
Multicenter Phase II Study of Whole-Body and Intracranial Activity With Ceritinib in Patients With ALK-Rearranged Non-Small-Cell Lung Cancer Previously Treated With Chemotherapy and Crizotinib: Results From ASCEND-2.
CrinòL, Ahn MJ, De Marinis F, Groen HJ, Wakelee H, Hida T, Mok T, Spigel D, Felip E, Nishio M, Scagliotti G, Branle F, Emeremni C, Quadrigli M, Zhang J, Shaw AT
J Clin Oncol. 2016 Aug;34(24):2866-73. Epub 2016 Jul 18.
PURPOSE: Phase I data (ASCEND-1) showed ceritinib efficacy in patients with ALK-rearranged non-small-cell lung cancer (NSCLC), regardless of brain metastases status and with or without prior therapy with an inhibitor of the ALK protein.Data are presented from a phase II trial (ASCEND-2) in which ceritinib efficacy and safety were evaluated in patients who had ALK-rearranged NSCLC previously treated with at least one platinum-based chemotherapy and who had experienced progression during crizotinib treatment as their last prior therapy.
PATIENTS AND METHODS: Patients with advanced ALK-rearranged NSCLC, including those with asymptomatic or neurologically stable baseline brain metastases, received oral ceritinib 750 mg/d. Whole-body and intracranial responses were investigator assessed (according to RECIST version 1.1). Patient-reported outcomes were evaluated with the Lung Cancer Symptom Scale and European Organisation for Research and Treatment of Cancer surveys (the core-30 and the 13-item lung cancer-specific quality-of-life questionnaires).
RESULTS: All 140 patients enrolled had received two or more previous treatment regimens, and all patients had received crizotinib. The median duration of exposure and the follow-up time with ceritinib were 8.8 months (range, 0.1 to 19.4 months) and 11.3 months (range, 0.1 to 18.9 months), respectively. Investigator-assessed overall response rate was 38.6% (95% CI, 30.5% to 47.2%). Secondary end points, all investigator assessed, included disease control rate (77.1%; 95% CI, 69.3% to 83.8%), time to response (median, 1.8 months; range, 1.6 to 5.6 months), duration of response (median, 9.7 months; 95% CI, 7.1 to 11.1 months), and progression-free survival (median, 5.7 months; 95% CI, 5.4 to 7.6 months). Of 100 patients with baseline brain metastases, 20 had active target lesions at baseline; investigator-assessed intracranial overall response rate was 45.0% (95% CI, 23.1% to 68.5%). The most common adverse events (majority, grade 1or 2) for all treated patients were nausea (81.4%), diarrhea (80.0%), and vomiting (62.9%). Patient-reported outcomes showed a trend toward improved symptom burden. The global quality-of-life score was maintained during treatment.
CONCLUSION: Consistent with its activity in ASCEND-1, ceritinib treatment provided clinically meaningful and durable responses with manageable tolerability in chemotherapy- and crizotinib-pretreated patients, including those with brain metastases.
Lucio Crinò, University Medical School of Perugia, Azienda Ospedale Perugia, Perugia; Filippo De Marinis, European Institute of Oncology, Milan; Giorgio Scagliotti, University of Torino, Torino, Italy; Myung-Ju Ahn, Sungkyunkwan University School of Medicine, Samsung Medical Center, Seoul, South Korea; Harry J.M. Groen, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands; Heather Wakelee, Stanford University Medical Center, Stanford, CA; Toyoaki Hida, Aichi Cancer Center, Nagoya; Makoto Nishio, Japanese Foundation for Cancer Research, Tokyo, Japan; Tony Mok, Chinese University of Hong Kong, Shatin, China; David Spigel, Sarah Cannon Research Institute, Nashville, TN; Enriqueta Felip, Vall d'Hebron University, Barcelona, Spain; Fabrice Branle and Massimiliano Quadrigli, Novartis Pharma AG, Basel, Switzerland; Chetachi Emeremni and Jie Zhang, Novartis Pharma, East Hanover, NJ; and Alice T. Shaw, Massachusetts General Hospital, Boston MA. email@example.com.
Ceritinib (LDK378): a potent alternative to crizotinib for ALK-rearranged non-small-cell lung cancer.
Li S, Qi X, Huang Y, Liu D, Zhou F, Zhou C
Clin Lung Cancer. 2015 Mar;16(2):86-91. Epub 2014 Oct 13.
The success in identifying the chromosomal rearrangements involving the anaplastic lymphoma kinase (ALK) as an oncogenic driver has thoroughly changed the treatment of non-small-cell lung cancer. In the past decade, targeted drugs have emerged as an efficient personalized strategy for ALK-rearranged non-small-cell lung cancer. The accelerated approval of potent ALK inhibitors, such as crizotinib and more recently ceritinib (LDK378), based on the well designed phase I/II trials has been a landmark success in clinical cancer research and contributes a new era of oncogenic targeted therapy characterized by elegant clinical trial design. In this review, we aim to present the current knowledge on acquired resistance of crizotinib known as a first-in-class ALK inhibitor and potential solutions to improve the cost-effectiveness, and to review the difference between ceritinib and crizotinib; preclinical data and results of the elegant early clinical trial of ceritinib which promoted its accelerated approval, pharmacokinetics, safety profile, and tolerability, the updated results (eg, efficacy on brain metastases), and robust design of ongoing phase II/III trials, and future directions of ceritinib to be a potent alternative to crizotinib for ALK-rearranged non-small-cell lung cancer are also presented.
Department of Spine Surgery, the Affiliated Hospital of Luzhou Medical College, Luzhou, China. Electronic address: firstname.lastname@example.org.
Brigatinib (BRG) in patients (pts) with crizotinib (CRZ)-refractory ALK+ non-small cell lung cancer (NSCLC): First report of efficacy and safety from a pivotal randomized phase (ph) 2 trial (ALTA).
Kim DW, Tiseo M, Ahn MJ, Reckamp KL
J Clin Oncol. 2016;34S: ASCO #9007