Makoto Nishio1, Enriqueta Felip2, Sergey Orlov3, Keunchil Park4, Chong-Jen Yu5, Chun-Ming Tsai6, Manuel Cobo7, Mark McKeage8, Wu-Chou Su9, Tony Mok10, Giorgio V Scagliotti11, David R Spigel12, Kalyanee Viraswami-Appanna13, Zhe Chen13, Vanessa Q Passos13, Alice T Shaw14. 1. Thoracic Medical Oncology Department, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan. Electronic address: mnishio@jfcr.or.jp. 2. Department of Medical Oncology, Vall d'Hebron University Hospital and Vall d'Hebron Institute of Oncology, Barcelona, Spain. 3. Department of Thoracic Oncology, Pavlov First Saint Petersburg State Medical University, St. Petersburg, Russia. 4. Division of Hematology and Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea. 5. Department of Internal Medicine, National Taiwan University, Taipei, Taiwan. 6. Department of Oncology, Taipei Veterans General Hospital, Taipei, Taiwan. 7. Medical Oncology Department, Hospital Regional Universitario Málaga, Instituto de Investigaciones Biomédicas, Málaga, Spain. 8. Division of Pharmacology and Clinical Pharmacology, Auckland City Hospital and University of Auckland, Auckland, New Zealand. 9. Department of Internal Medicine, National Cheng Kung University Hospital, Tainan, Taiwan. 10. Department of Clinical Oncology, The Chinese University of Hong Kong, Shatin, The People's Republic of China. 11. Department of Oncology, University of Torino, Orbassano, Torino, Italy. 12. Medical Oncology, Sarah Cannon Research Institute, Nashville, Tennessee. 13. Novartis Pharmaceuticals Corporation, East Hanover, New Jersey. 14. Department of Medicine and Pathology, Massachusetts General Hospital, Boston, Massachusetts.
Abstract
INTRODUCTION: The phase II, single-arm ASCEND-3 study assessed the efficacy and safety of ceritinib in anaplastic lymphoma kinase (ALK) inhibitor (ALKi)-naive patients with ALK-rearranged NSCLC who had received at least three previous lines of chemotherapy. Here, we report the final efficacy and safety results. METHODS: Eligible patients (including those with asymptomatic or neurologically stable brain metastases) received oral ceritinib (750 mg/day, fasted). The primary end point was investigator-assessed overall response rate (ORR). Secondary end points were Blinded Independent Review Committee-assessed ORR; investigator- and Blinded Independent Review Committee-assessed overall intracranial response rate, duration of response, time to response, disease control rate, and progression-free survival (PFS); overall survival (OS); and safety. Exploratory end points included patient-reported outcomes. RESULTS: Of the 124 patients enrolled, 122 (98.4%) had received previous antineoplastic medications (31 patients [25.0%] received at least three regimens), and 49 (39.5%) had baseline brain metastases. The median follow-up time (data cutoff: January 22, 2018) was 52.1 (range, 48.4-60.1) months. The investigator-assessed ORR was 67.7% (95% confidence interval [CI]: 58.8-75.9), and the median PFS was 16.6 months (95% CI: 11.0-23.2). The median OS was 51.3 months (95% CI: 42.7-55.3). Most common adverse events (all grades, ≥60% of patients, all-causality) were diarrhea (85.5%), nausea (78.2%), and vomiting (71.8%). Overall, 18 patients (14.5%) had an adverse event leading to treatment discontinuation. Health-related quality of life was maintained during ceritinib treatment. CONCLUSIONS: Ceritinib exhibited prolonged and clinically meaningful OS, PFS, and duration of response in chemotherapy-pretreated (at least three lines), ALKi-naive patients with ALK+ NSCLC. The safety profile was consistent with that reported in previous studies.
INTRODUCTION: The phase II, single-arm ASCEND-3 study assessed the efficacy and safety of ceritinib in anaplastic lymphoma kinase (ALK) inhibitor (ALKi)-naive patients with ALK-rearranged NSCLC who had received at least three previous lines of chemotherapy. Here, we report the final efficacy and safety results. METHODS: Eligible patients (including those with asymptomatic or neurologically stable brain metastases) received oral ceritinib (750 mg/day, fasted). The primary end point was investigator-assessed overall response rate (ORR). Secondary end points were Blinded Independent Review Committee-assessed ORR; investigator- and Blinded Independent Review Committee-assessed overall intracranial response rate, duration of response, time to response, disease control rate, and progression-free survival (PFS); overall survival (OS); and safety. Exploratory end points included patient-reported outcomes. RESULTS: Of the 124 patients enrolled, 122 (98.4%) had received previous antineoplastic medications (31 patients [25.0%] received at least three regimens), and 49 (39.5%) had baseline brain metastases. The median follow-up time (data cutoff: January 22, 2018) was 52.1 (range, 48.4-60.1) months. The investigator-assessed ORR was 67.7% (95% confidence interval [CI]: 58.8-75.9), and the median PFS was 16.6 months (95% CI: 11.0-23.2). The median OS was 51.3 months (95% CI: 42.7-55.3). Most common adverse events (all grades, ≥60% of patients, all-causality) were diarrhea (85.5%), nausea (78.2%), and vomiting (71.8%). Overall, 18 patients (14.5%) had an adverse event leading to treatment discontinuation. Health-related quality of life was maintained during ceritinib treatment. CONCLUSIONS:Ceritinib exhibited prolonged and clinically meaningful OS, PFS, and duration of response in chemotherapy-pretreated (at least three lines), ALKi-naive patients with ALK+ NSCLC. The safety profile was consistent with that reported in previous studies.
Authors: Malinda Itchins; Brandon Lau; Amanda L Hudson; Helen Westman; Cathy Yi Xia; Sarah A Hayes; Viive M Howell; Michael Rodriguez; Wendy A Cooper; Heng Wei; Michael Buckland; Bob T Li; Mark Li; Vivek Rathi; Stephen B Fox; Anthony J Gill; Stephen J Clarke; Michael J Boyer; Nick Pavlakis Journal: Oncologist Date: 2020-07-02
Authors: Daniel S W Tan; Sarayut Geater; Chong-Jen Yu; Chun-Ming Tsai; Te-Chun Hsia; Jun Chen; Meng-Chih Lin; You Lu; Virote Sriuranpong; Cheng-Ta Yang; Paramita Sen; Fabrice Branle; Michael Shi; Yi-Long Wu Journal: JTO Clin Res Rep Date: 2020-12-17
Authors: Anna L McGuire; Melissa K McConechy; Barb L Melosky; John C English; James J Choi; Defen Peng; John Yee; Benjamin L S Furman; Rosalia Aguirre Hernandez; Pedro Feijao; David Mulder; Curtis Hughesman; Stephen Yip Journal: Curr Oncol Date: 2022-04-11 Impact factor: 3.109