TY - JOUR
T1 - Final Overall Survival and Other Efficacy and Safety Results From ASCEND-3
T2 - Phase II Study of Ceritinib in ALKi-Naive Patients With ALK-Rearranged NSCLC
AU - Nishio, Makoto
AU - Felip, Enriqueta
AU - Orlov, Sergey
AU - Park, Keunchil
AU - Yu, Chong Jen
AU - Tsai, Chun Ming
AU - Cobo, Manuel
AU - McKeage, Mark
AU - Su, Wu Chou
AU - Mok, Tony
AU - Scagliotti, Giorgio V.
AU - Spigel, David R.
AU - Viraswami-Appanna, Kalyanee
AU - Chen, Zhe
AU - Passos, Vanessa Q.
AU - Shaw, Alice T.
N1 - Funding Information:
This study was funded by Novartis Pharmaceuticals Corporation . The authors thank the participating patients, their families, all study coinvestigators, and research coordinators. In addition, the authors thank Vanessa Giannone, Novartis Healthcare Pvt. Ltd. (East Hanover, United States), for her contribution to this study. Medical writing support was provided by Shilpa Garg, Novartis Healthcare Pvt. Ltd. (Hyderabad, India).
Funding Information:
This study was funded by Novartis Pharmaceuticals Corporation. The authors thank the participating patients, their families, all study coinvestigators, and research coordinators. In addition, the authors thank Vanessa Giannone, Novartis Healthcare Pvt. Ltd. (East Hanover, United States), for her contribution to this study. Medical writing support was provided by Shilpa Garg, Novartis Healthcare Pvt. Ltd. (Hyderabad, India). Disclosure: Dr. Viraswami-Appanna and Dr. Passos are employees of and own stocks in Novartis. Dr. Chen was an employee of Novartis at the time of analysis and initiation of the manuscript and owned stock in Novartis. Dr. Nishio has received research funding from Novartis, Ono Pharmaceutical, MSD, Chugai Pharmaceutical, BMS, Taiho Pharmaceutical, Eli Lilly, Pfizer, Astellas Pharma, and AZ, and has acted as an advisor and a consultant for MSD, Novartis, Pfizer, BMS, Ono Pharmaceutical, Chugai Pharmaceutical, Eli Lilly, Taiho Pharmaceutical, Astellas, and AZ. Dr. Felip has acted as an advisor and a consultant for AbbVie, AZ, BerGenBio, Blue Print Medicines, BI, BMS, Celgene, Eli Lilly, Guardant Health, Janssen, Medscape, Merck KGaA, MSD, Novartis, Pfizer, Prime Oncology, Roche, Samsung, Takeda, and Touchtime; received research funding from Fundacion Merck Salud and Grant for Oncology Innovation EMD Serono; and has been compensated for a leadership role at Grifols. Dr. Orlov has acted as an advisor and a consultant for BMS, BI, MSD, Novartis, and Roche. Dr. Park has acted as an advisor and a consultant for Amgen, Astellas, AZ, BluePrint Medicines, BI, BMS, Clovis, Eli Lilly, Hanmi, KHK, Loxo, Merck KGaA, MSD, Novartis, Ono Pharmaceutical, and Roche; participated in a speakers? bureau for AZ and BI; and received research funding from AZ and MSD. Dr. Yu has acted as an advisor and a consultant for AZ, BI, Novartis, GSK, MSD, Ono Pharmaceutical, and Roche. Dr. Tsai has acted as an advisorand a consultant for Novartis, Pfizer, Roche, Eli Lilly, MSD, BMS, and AZ and has received honoraria from Novartis, Pfizer, Roche, Eli Lilly, MSD, BMS, and AZ. Dr. McKeage has acted as an advisor and a consultant for Novartis and Pfizer and has received research funding from Pfizer. Dr. Mok is a current employee at The Chinese University of Hong Kong; has been compensated for a leadership role at AZ PLC and Hutchison Chi-Med; owns stocks of Hutchison Chi-Med and Sanomics; has received honoraria from ACEA Pharma, Alpha Biopharma Co., Amgen, Amoy Diagnostics Co., AZ, Bayer, BI, Blueprint Medicines, BMS, Celgene, CStone Pharmaceuticals, Eli Lilly, Fishawack Facilitate, Hengrui Therapeutics, Ignyta, Incyte Corporation, InMed Medical Communication, IQVIA, Janssen, Loxo Oncology, Merck Serono, MSD, MoreHealth, Novartis, OncoGenex Pharmaceuticals, OrigiMed, PeerVoice, Pfizer, Prime Oncology, Roche and Genentech, Sanofi-Aventis R&D, SFJ Pharmaceutical, Takeda Pharmaceuticals HK, Vertex Pharmaceuticals, and Yuhan Corporation; has acted as an advisor and a consultant for ACEA Pharma, Alpha Biopharma Co., Amgen, Amoy Diagnostics Co., AZ, Bayer, BI, Blueprint Medicines, BMS, Celgene, Cirina, CStone Pharmaceuticals, Eli Lilly, Fishawack Facilitate, geneDecode Co., Hengrui Therapeutics, Ignyta, Incyte Corporation, InMed Medical Communication, IQVIA, Janssen, Loxo Oncology, Merck Serono, MSD, MoreHealth, Novartis, OncoGenex Pharmaceuticals, OrigiMed, PeerVoice, Pfizer, Prime Oncology, Roche and Genentech, Sanofi-Aventis R&D, SFJ Pharmaceutical, Takeda Pharmaceuticals HK, Vertex Pharmaceuticals, and Yuhan Corporation; has participated in a speakers? bureau for ACEA Pharma, Alpha Biopharma Co., Amgen, Amoy Diagnostics Co., AstraZeneca, BI, BMS, Eli Lilly, InMed Medical Communication, MSD, Novartis, Pfizer, Prime Oncology, Roche and Genentech, Taiho, and Takeda Oncology; and has received research funding from AZ, BMS, Clovis Oncology, MSD, Novartis, Pfizer, Roche, SFJ, and XCovery. Dr. Scagliotti has acted as a consultant for MSD and Eli Lilly and has received honoraria from Eli Lilly, AZ, Roche, and AbbVie. Dr. Spigel has been compensated for a leadership role at the Centennial Medical Center; has acted as an advisor and a consultant for Genentech and Roche, Novartis, Celgene, BMS, AZ, Pfizer, BI, AbbVie, Foundation Medicine, GSK, Lilly, Merck, Moderna Therapeutics, Nektar, Takeda, Amgen, TRM Oncology, Precision Oncology, Evelo Therapeutics, Illumina, and PharmaMar; has received research funding from Genentech and Roche, Novartis, Celgene, BMS, Lilly, AZ, Pfizer, BI, University of Texas Southwestern Medical Center-Simmons Cancer Center, Merck, AbbVie, GSK, G1 Therapeutics, Neon Therapeutics, Takeda, Foundation Medicine, Nektar, Celldex, Clovis Oncology, Daiichi Sankyo, EMD Serono, Acerta Pharma, Oncogenex, Astellas Pharma, Grail, Transgene, Aeglea Biotherapeutics, Tesaro, Ipsen, ARMO BioSciences, Amgen, and Millennium; and has received travel support from AZ, BI, Celgene, Lilly, EMD Serono, BMS, Genentech, Genzyme, Intuitive Surgical, Merck, Pfizer, Purdue Pharma, Spectrum Pharmaceuticals, and Sysmex. Dr. Shaw has served as a compensated consultant or received honoraria from Achilles, ARIAD, Bayer, Blueprint Medicines, Chugai, Daiichi Sankyo, EMD Serono, Foundation Medicine, Genentech/Roche, Guardant, Ignyta, KSQ Therapeutics, Loxo, Natera, Novartis, Pfizer, Servier, Taiho Pharmaceutical, Takeda, and TP Therapeutics; has received research funding from Daiichi Sankyo, Ignyta, Novartis, Pfizer, Roche and Genentech, and TP Therapeutics; and has received travel support from Pfizer and Genentech and Roche. The remaining authors have nothing to disclose.
Publisher Copyright:
© 2019 International Association for the Study of Lung Cancer
PY - 2020/4
Y1 - 2020/4
N2 - 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.
AB - 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.
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U2 - 10.1016/j.jtho.2019.11.006
DO - 10.1016/j.jtho.2019.11.006
M3 - Article
C2 - 31778798
AN - SCOPUS:85078128722
SN - 1556-0864
VL - 15
SP - 609
EP - 617
JO - Journal of Thoracic Oncology
JF - Journal of Thoracic Oncology
IS - 4
ER -