Long-Term Efficacy and Safety of Entrectinib in ROS1 Fusion–Positive NSCLC

Alexander Drilon, MD; Chao-Hua Chiu, MD; Yun Fan, MD; Byoung Chul Cho, MD, PhD; Shun Lu, MD, PhD; Myung-Ju Ahn, MD, PhD; Matthew G. Krebs, MD, PhD; Stephen V. Liu, MD; Thomas John, MD; Gregory A. Otterson, MD; Daniel S.W. Tan, MD; Tejas Patil, MD; Rafal Dziadziuszko, MD, PhD; Erminia Massarelli, MD, PhD; Takashi Seto, MD; Robert C. Doebele, MD, PhD; Bethany Pitcher, MSc; Nino Kurtsikidze, MD; Sebastian Heinzmann, PhD; Salvatore Siena, MD

JTO Clinical and Research Reports (Jun 2022)

Long-Term Efficacy and Safety of Entrectinib in ROS1 Fusion–Positive NSCLC

Alexander Drilon, MD,
Chao-Hua Chiu, MD,
Yun Fan, MD,
Byoung Chul Cho, MD, PhD,
Shun Lu, MD, PhD,
Myung-Ju Ahn, MD, PhD,
Matthew G. Krebs, MD, PhD,
Stephen V. Liu, MD,
Thomas John, MD,
Gregory A. Otterson, MD,
Daniel S.W. Tan, MD,
Tejas Patil, MD,
Rafal Dziadziuszko, MD, PhD,
Erminia Massarelli, MD, PhD,
Takashi Seto, MD,
Robert C. Doebele, MD, PhD,
Bethany Pitcher, MSc,
Nino Kurtsikidze, MD,
Sebastian Heinzmann, PhD,
Salvatore Siena, MD

Affiliations

Alexander Drilon, MD: Department of Medicine, Memorial Sloan Kettering Cancer Center, and Weill Cornell Medical College, New York, New York
Chao-Hua Chiu, MD: Department of Chest Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
Yun Fan, MD: Zhejiang Cancer Hospital, Hangzhou, People’s Republic of China
Byoung Chul Cho, MD, PhD: Division of Medical Oncology, Yonsei Cancer Center, Seoul, Republic of Korea
Shun Lu, MD, PhD: Department of Medical Oncology, Shanghai Lung Cancer Center, Shanghai Chest Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People’s Republic of China
Myung-Ju Ahn, MD, PhD: Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
Matthew G. Krebs, MD, PhD: Division of Cancer Sciences, Faculty of Biology, Medicine and Health, The University of Manchester and The Christie National Health Service (NHS) Foundation Trust, Manchester Academic Health Science Centre, Manchester, United Kingdom
Stephen V. Liu, MD: Georgetown University, Washington, District of Columbia
Thomas John, MD: Department of Medical Oncology, Peter MacCallum Cancer Center, and Olivia Newton-John Cancer Centre, Austin Health, Melbourne, Australia
Gregory A. Otterson, MD: Arthur G. James Cancer Hospital, and Richard J. Solove Research Institute, The Ohio State University Comprehensive Cancer Center, Columbus, Ohio
Daniel S.W. Tan, MD: Division of Medical Oncology, National Cancer Centre Singapore, Duke–National University of Singapore (NUS) Medical School, Singapore
Tejas Patil, MD: Division of Medical Oncology, Department of Medicine, University of Colorado, Aurora, Colorado
Rafal Dziadziuszko, MD, PhD: Department of Oncology and Radiotherapy and Early Clinical Trials Center, Medical University of Gdansk, Gdansk, Poland
Erminia Massarelli, MD, PhD: Department of Medical Oncology & Therapeutics Research, City of Hope Comprehensive Cancer Center, Duarte, California
Takashi Seto, MD: Department of Thoracic Oncology, National Hospital Organization Kyushu Cancer Center, Fukuoka, Japan
Robert C. Doebele, MD, PhD: Division of Medical Oncology, Department of Medicine, University of Colorado, Aurora, Colorado
Bethany Pitcher, MSc: F. Hoffmann-La Roche Ltd, Mississauga, Canada
Nino Kurtsikidze, MD: F. Hoffmann-La Roche Ltd, Basel, Switzerland
Sebastian Heinzmann, PhD: Niguarda Cancer Center, Grande Ospedale Metropolitano Niguarda, Milan, Italy
Salvatore Siena, MD: Niguarda Cancer Center, Grande Ospedale Metropolitano Niguarda, Milan, Italy; Department of Oncology and Hemato-Oncology, Università degli Studi di Milano, Milan, Italy; Corresponding author. Address for correspondence: Salvatore Siena, MD, Department of Oncology and Hemato-Oncology, Università degli Studi di Milano (La Statale), Ospedale Niguarda, Piazza Ospedale Maggiore 2, 20146 Milano, Italy.

Journal volume & issue: Vol. 3, no. 6
p. 100332

Abstract

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Introduction: Entrectinib is an approved tyrosine kinase inhibitor (TKI) for ROS1 fusion–positive NSCLC. An updated integrated analysis of entrectinib from the ALKA-372-001, STARTRK-1, and STARTRK-2 trials is presented, with substantially longer follow-up, more patients, and the first description of the median overall survival (OS). An exploratory analysis of entrectinib in ROS1 fusion–positive NSCLC with the central nervous system (CNS)–only progression post-crizotinib is reported. Methods: Adults with ROS1 fusion–positive, locally advanced or metastatic NSCLC who received at least one dose of entrectinib and had 12 months or longer of follow-up were included in the analysis. Co-primary end points were confirmed objective response rate (ORR) and duration of response (DoR) by blinded independent central review. The data cutoff was on August 31, 2020. Results: The efficacy-assessable population comprised 168 ROS1 TKI–naïve patients. The median survival follow-up was 29.1 months (interquartile range, 21.8–35.9). The ORR was 68% (95% confidence interval [CI]: 60.2–74.8); the median DoR was 20.5 months. The median progression-free survival (PFS) was 15.7 months and the median OS was 47.8 months. In the 25 patients with measurable baseline CNS metastases, the intracranial ORR was 80% (95% CI: 59.3–93.2), median intracranial DoR was 12.9 months, and median intracranial PFS was 8.8 months. Among 18 patients with CNS-only progression on previous crizotinib treatment, two achieved a partial response (11%) and four had stable disease (22%). In seven patients with measurable CNS disease from this cohort, the intracranial ORR was 14% (1 partial response). Conclusions: Entrectinib is active and achieves prolonged survival in ROS1 TKI–naïve patients with ROS1 fusion–positive NSCLC. Modest activity is seen in patients with CNS-only progression post-crizotinib.

Published in JTO Clinical and Research Reports

ISSN: 2666-3643 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Medicine: Internal medicine: Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Website: https://www.journals.elsevier.com/jto-clinical-and-research-reports/

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