TY - JOUR
T1 - ASCEND-7
T2 - Efficacy and Safety of Ceritinib Treatment in Patients with ALK-Positive Non-Small Cell Lung Cancer Metastatic to the Brain and/or Leptomeninges
AU - Chow, Laura Q.M.
AU - Barlesi, Fabrice
AU - Bertino, Erin M.
AU - Van Den Bent, Martin J.
AU - Wakelee, Heather A.
AU - Wen, Patrick Y.
AU - Chiu, Chao Hua
AU - Orlov, Sergey
AU - Chiari, Rita
AU - Majem, Margarita
AU - McKeage, Mark
AU - Yu, Chong Jen
AU - Garrido, Pilar
AU - Hurtado, Felipe K.
AU - Arratia, Pilar Cazorla
AU - Song, Yuanbo
AU - Branle, Fabrice
AU - Shi, Michael
AU - Kim, Dong Wan
N1 - Funding Information:
L.Q.M. Chow reports grants, personal fees, and nonfinancial support from Novartis during the conduct of the study as well as grants and personal fees from Alkermes, Merck, AstraZeneca, Pfizer, and Dynavax; grants from Oncorus, Lily/Imclone, Bristol Myers Squibb, Seattle Genetics, and Genentech; and personal fees from Sanofi-Genzyme, EMD Serono, Daiichi Sankyo, Ipsen, Nanobiotix/Life Sciences Dynamic, Regeneron, Blueprint Therapeutics, Beigene, Elicio Therapeutics, Gilead, and Cullinan-Apollo Corp outside the submitted work. F. Barlesi reports personal fees from AstraZeneca, Bayer, Bristol-Myers Squibb, Boehringer-Ingelheim, Eli Lilly Oncology, F. Hoffmann-La Roche Ltd, Novartis, Merck, Mirati, MSD, Pierre Fabre, Pfizer, Seattle Genetics, and Takeda outside the submitted work. E.M. Bertino reports personal fees from Pfizer and Dava Oncology during the conduct of the study as well as personal fees from Pfizer, Intellosphere, and Bristol Myers Squibb, and nonfinancial support from Merck and Lilly outside the submitted work. H.A. Wakelee reports grants from Novartis during the conduct of the study as well as grants from Arrys Therapeutics, Celgene, Clovis, Genentech/Roche, Merck, Pfizer, Exelixis, Gilead, and Pharmacyclics, and grants and personal fees from Xcovery and Mirati outside the submitted work. P.Y. Wen reports other support from Agios, AstraZeneca/Medimmune, Beigene, Celgene, Eli Lilly, Genentech/Roche, Kazia, MediciNova, Merck, Novartis, Nuvation Bio, Oncoceutics, Vascular Biogenics, VBI Vaccines, AstraZeneca, Bayer, Boston Pharmaceuticals, CNS Pharmaceuticals, Elevate Bio Immunomic Therapeutics, Imvax, Karyopharm, Voyager, QED, Celularity, and Sapience outside the submitted work. C.-H. Chiu reports personal fees from Novartis during the conduct of the study as well as personal fees from
Funding Information:
This study was funded by Novartis Pharmaceuticals Corporation. The authors thank the patients, their families and caregivers, and the investigators who participated in the study. Medical writing and editorial assistance was provided by Aarti Kamaraj and Manoj Kumar Patel (Novartis Healthcare Pvt. Ltd.).
Publisher Copyright:
© 2022 American Association for Cancer Research.
PY - 2022/6
Y1 - 2022/6
N2 - Purpose:Central nervous systemmetastases are a prominent cause of morbidity and mortality in patients with ALK-positive (ALK+) non-small cell lung cancer (NSCLC). The phase II ASCEND-7 (NCT02336451) study was specifically designed to assess the efficacy and safety of the ALK inhibitor (ALKi) ceritinib in patients with ALK+ NSCLC metastatic to the brain and/or leptomeninges. Patients and Methods: Patients with active brain metastases were allocated to study arms 1 to 4 based on prior exposure to an ALKi and/or prior brain radiation (arm 1: prior radiotherapy/ALKipretreated; arm 2: no radiotherapy/ALKi-pretreated; arm 3: prior radiotherapy/ALKi-naïve; arm 4: no radiotherapy/ALKi-naïve). Arm 5 included patients with leptomeningeal carcinomatosis. Patients received ceritinib 750 mg once daily (fasted condition). Primary endpoint was investigator-assessed whole-body overall response rate (ORR) per RECIST v1.1. Secondary endpoints included disease control rate (DCR) and intracranial/extracranial responses. Results: Per investigator assessment, in arms 1 (n = 42), 2 (n = 40), 3 (n = 12), and 4 (n = 44), respectively: whole-body ORRs [95% confidence interval (CI)] were 35.7% (21.6-52.0), 30.0% (16.6-46.5), 50.0% (21.1-78.9), and 59.1% (43.2-73.7); whole-body DCR (95% CI): 66.7% (50.5-80.4), 82.5% (67.2- 92.7), 66.7% (34.9-90.1), and 70.5% (54.8-83.2); intracranial ORRs (95% CI): 39.3% (21.5-59.4), 27.6% (12.7-47.2), 28.6% (3.7-71.0), and 51.5% (33.5-69.2). In arm 5 (n = 18), whole-body ORR was 16.7% (95% CI, 3.6-41.4) and DCR was 66.7% (95% CI, 41.0-86.7). Paired cerebrospinal fluid and plasma sampling revealed that ceritinib penetrated the human blood-brain barrier. Conclusions: Ceritinib showed antitumor activity in patients with ALK+ NSCLC with active brain metastases and/or leptomeningeal disease, and could be considered in the management of intracranial disease.
AB - Purpose:Central nervous systemmetastases are a prominent cause of morbidity and mortality in patients with ALK-positive (ALK+) non-small cell lung cancer (NSCLC). The phase II ASCEND-7 (NCT02336451) study was specifically designed to assess the efficacy and safety of the ALK inhibitor (ALKi) ceritinib in patients with ALK+ NSCLC metastatic to the brain and/or leptomeninges. Patients and Methods: Patients with active brain metastases were allocated to study arms 1 to 4 based on prior exposure to an ALKi and/or prior brain radiation (arm 1: prior radiotherapy/ALKipretreated; arm 2: no radiotherapy/ALKi-pretreated; arm 3: prior radiotherapy/ALKi-naïve; arm 4: no radiotherapy/ALKi-naïve). Arm 5 included patients with leptomeningeal carcinomatosis. Patients received ceritinib 750 mg once daily (fasted condition). Primary endpoint was investigator-assessed whole-body overall response rate (ORR) per RECIST v1.1. Secondary endpoints included disease control rate (DCR) and intracranial/extracranial responses. Results: Per investigator assessment, in arms 1 (n = 42), 2 (n = 40), 3 (n = 12), and 4 (n = 44), respectively: whole-body ORRs [95% confidence interval (CI)] were 35.7% (21.6-52.0), 30.0% (16.6-46.5), 50.0% (21.1-78.9), and 59.1% (43.2-73.7); whole-body DCR (95% CI): 66.7% (50.5-80.4), 82.5% (67.2- 92.7), 66.7% (34.9-90.1), and 70.5% (54.8-83.2); intracranial ORRs (95% CI): 39.3% (21.5-59.4), 27.6% (12.7-47.2), 28.6% (3.7-71.0), and 51.5% (33.5-69.2). In arm 5 (n = 18), whole-body ORR was 16.7% (95% CI, 3.6-41.4) and DCR was 66.7% (95% CI, 41.0-86.7). Paired cerebrospinal fluid and plasma sampling revealed that ceritinib penetrated the human blood-brain barrier. Conclusions: Ceritinib showed antitumor activity in patients with ALK+ NSCLC with active brain metastases and/or leptomeningeal disease, and could be considered in the management of intracranial disease.
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UR - http://www.scopus.com/inward/citedby.url?scp=85131604877&partnerID=8YFLogxK
U2 - 10.1158/1078-0432.CCR-21-1838
DO - 10.1158/1078-0432.CCR-21-1838
M3 - Article
C2 - 35091443
AN - SCOPUS:85131604877
SN - 1078-0432
VL - 28
SP - 2506
EP - 2516
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 12
ER -
