Final Overall Survival and Other Efficacy and Safety Results From ASCEND-3: Phase II Study of Ceritinib in ALKi-Naive Patients With ALK-Rearranged NSCLC.

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.

• Authors: Makoto Nishio, Enriqueta Felip, Sergey Orlov, Keunchil Park, Chong-Jen Yu, Chun-Ming Tsai, Manuel Cobo, Mark McKeage, Wu-Chou Su, Tony Mok, Giorgio V Scagliotti, David R Spigel, Kalyanee Viraswami-Appanna, Zhe Chen, Vanessa Q Passos, Alice T Shaw
• Journal: Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer (J Thorac Oncol) Vol. 15 Issue 4 Pg. 609-617 (04 2020) ISSN: 1556-1380 [Electronic] United States
• PMID: 31778798 (Publication Type: Clinical Trial, Phase II, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2019 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

Chemical References

• Antineoplastic Agents
• Protein Kinase Inhibitors
• Pyrimidines
• Sulfones
• Anaplastic Lymphoma Kinase
• Receptor Protein-Tyrosine Kinases
• ceritinib

Topics

• Anaplastic Lymphoma Kinase (genetics)
• Antineoplastic Agents (therapeutic use)
• Humans
• Lung Neoplasms (drug therapy, genetics)
• Protein Kinase Inhibitors (therapeutic use)
• Pyrimidines
• Quality of Life
• Receptor Protein-Tyrosine Kinases
• Sulfones