title: 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.
abstract: 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 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).
  
  
  
  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.
  
  
  
  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.
authors.affiliation: 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.
authors.forename: Lucio
authors.initials: L
authors.lastname: Crinò
authors.affiliation: 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.
authors.forename: Myung-Ju
authors.initials: MJ
authors.lastname: Ahn
authors.affiliation: 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.
authors.forename: Filippo
authors.initials: F
authors.lastname: De Marinis
authors.affiliation: 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.
authors.forename: Harry J M
authors.initials: HJ
authors.lastname: Groen
authors.affiliation: 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.
authors.forename: Heather
authors.initials: H
authors.lastname: Wakelee
authors.affiliation: 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.
authors.forename: Toyoaki
authors.initials: T
authors.lastname: Hida
authors.affiliation: 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.
authors.forename: Tony
authors.initials: T
authors.lastname: Mok
authors.affiliation: 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.
authors.forename: David
authors.initials: D
authors.lastname: Spigel
authors.affiliation: 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.
authors.forename: Enriqueta
authors.initials: E
authors.lastname: Felip
authors.affiliation: 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.
authors.forename: Makoto
authors.initials: M
authors.lastname: Nishio
authors.affiliation: 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.
authors.forename: Giorgio
authors.initials: G
authors.lastname: Scagliotti
authors.affiliation: 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.
authors.forename: Fabrice
authors.initials: F
authors.lastname: Branle
authors.affiliation: 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.
authors.forename: Chetachi
authors.initials: C
authors.lastname: Emeremni
authors.affiliation: 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.
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Quadrigli
authors.affiliation: 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.
authors.forename: Jie
authors.initials: J
authors.lastname: Zhang
authors.affiliation: 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.
authors.forename: Alice T
authors.initials: AT
authors.lastname: Shaw
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000077548:Anaplastic Lymphoma Kinase; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics / Q000556:secondary*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D000077547:Crizotinib; D005260:Female; D023061:Gene Order; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D047428:Protein Kinase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use; D011720:Pyrazoles / Q000008:administration & dosage; D011725:Pyridines / Q000008:administration & dosage; D011743:Pyrimidines / Q000009:adverse effects / Q000627:therapeutic use*; D020794:Receptor Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics*; D013450:Sulfones / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D009944:Organoplatinum Compounds; D047428:Protein Kinase Inhibitors; D011720:Pyrazoles; D011725:Pyridines; D011743:Pyrimidines; D013450:Sulfones; D000077547:Crizotinib; C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; D020794:Receptor Protein-Tyrosine Kinases; C586847:ceritinib