ASCEND-7: Efficacy and Safety of Ceritinib Treatment in Patients with <i>ALK</i>-Positive Non–Small Cell Lung Cancer Metastatic to the Brain and/or Leptomeninges-Reference-Cited by-同舟云学术

ASCEND-7: Efficacy and Safety of Ceritinib Treatment in Patients with ALK-Positive Non–Small Cell Lung Cancer Metastatic to the Brain and/or Leptomeninges

Published:2022-01-28 Issue:12 Volume:28 Page:2506-2516
ISSN:1078-0432
Container-title:Clinical Cancer Research
language:en
Short-container-title:

Author:

Chow Laura Q.M.¹^ORCID,Barlesi Fabrice²,Bertino Erin M.³^ORCID,van den Bent Martin J.⁴^ORCID,Wakelee Heather A.⁵^ORCID,Wen Patrick Y.⁶,Chiu Chao-Hua⁷,Orlov Sergey⁸,Chiari Rita⁹,Majem Margarita¹⁰^ORCID,McKeage Mark¹¹,Yu Chong-Jen¹²,Garrido Pilar¹³^ORCID,Hurtado Felipe K.¹⁴^ORCID,Arratia Pilar Cazorla¹⁴,Song Yuanbo¹⁴,Branle Fabrice¹⁵,Shi Michael¹⁴,Kim Dong-Wan¹⁶^ORCID

Affiliation:

1. 1University of Washington, Seattle, Washington and University of Texas at Austin, Dell Medical School, Department of Oncology, Austin, Texas.

2. 2Aix-Marseille University, CNRS, INSERM, CRCM, APHM, Marseille, France.

3. 3The Ohio State University Comprehensive Cancer Centre, Arthur G James Cancer Hospital and Richard J Solove Research Institute, Columbus, Ohio.

4. 4Department of Neurology, Erasmus MC Cancer Institute, University Medical Center Rotterdam, Rotterdam, the Netherlands.

5. 5Stanford University, Stanford, California.

6. 6Department of Medical Oncology, Dana Farber Cancer Institute, Boston, Massachusetts.

7. 7Department of Chest Medicine, Taipei Veterans General Hospital, National Yang-Ming University, Taipei, Taiwan.

8. 8State Pavlov Medical University, St. Petersburg, Russia.

9. 9Department of Oncology, AULSS6 Euganea, Padova, Italy.

10. 10Hospital de La Santa Creu I Sant Pau, Barcelona, Spain.

11. 11University of Auckland, Auckland, New Zealand.

12. 12Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.

13. 13Department of Medical Oncology, Hospital Universitario Ramon Y Cajal, Madrid, Spain.

14. 14Novartis Pharmaceuticals Corporation, East Hanover, New Jersey.

15. 15Novartis Pharma AG, Basel, Switzerland.

16. 16Department of Internal Medicine, Seoul National University College of Medicine and Seoul National University Hospital, Seoul, Republic of Korea.

Abstract

Abstract Purpose: Central nervous system metastases 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/ALKi-pretreated; 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. See related commentary by Murciano-Goroff et al., p. 2477

Publisher

American Association for Cancer Research (AACR)

Subject

Cancer Research,Oncology

Link

https://aacrjournals.org/clincancerres/article-pdf/28/12/2506/3154483/2506.pdf

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