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J Clin Oncol. 2016 Aug 20;34(24):2866-73. doi: 10.1200/JCO.2015.65.5936. Epub 2016 Jul 18.

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.

Author information

1
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. lucio.crino@ospedale.perugia.it.
2
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.

Abstract

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 1 or 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.

TRIAL REGISTRATION:

ClinicalTrials.gov NCT01685060.

PMID:
27432917
DOI:
10.1200/JCO.2015.65.5936
[Indexed for MEDLINE]

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