A noninferiority trial of cabozantinib (C) comparing 60 mg vs 140 mg orally per day to evaluate the efficacy and safety in patients (pts) with prog...

Date 21 October 2018
Event ESMO 2018 Congress
Session Poster display session: Basic science, Endocrine tumours, Gastrointestinal tumours - colorectal & non-colorectal, Head and neck cancer (excluding thyroid), Melanoma and other skin tumours, Neuroendocrine tumours, Thyroid cancer, Tumour biology & pathology
Topics Thyroid Cancer
Anticancer Agents
Presenter Jolanta Krajewska
Citation Annals of Oncology (2018) 29 (suppl_8): viii645-viii648. 10.1093/annonc/mdy302
Authors J. Krajewska1, B.G. Robinson2, B. Keam3, J. Capdevila Castillon4, A. Klochikhin5, H. Gan6, E. Kapiteijn7, R. Elisei8, J. Partyka9, A.E. Borgman9, M. Schlumberger10
  • 1Oncology Center, M. Sklodowska-Curie Institute, 44-101 - Gliwice/PL
  • 2Sydney Medical School, The University of Sydney, Sydney/AU
  • 3Internal Medicine, Seoul National University Hospital, 110-744 - Seoul/KR
  • 4Gastrointestinal And Endocrine Tumor Unit, Vall d'Hebron University Hospital, 08035 - Barcelona/ES
  • 5Oncology, Yaroslavl Regional Clinical Oncology Hospital, Yaroslavl/RU
  • 6Clinical Trials Austin Health, Olivia Newton-John Cancer Wellness & Research Centre, Heidelberg/AU
  • 7Medical Oncology, Leiden University Medical Center (LUMC), 2300 RC - Leiden/NL
  • 8Endocrine Unit, University Hospital of Pisa, Pisa/IT
  • 9Clinical research & Development, Exelixis, Inc, San Francisco/US
  • 10Department Of Nuclear Medicine And Endocrine Oncology, Gustave Roussy, Villejuif/FR

Abstract

Background

C inhibits receptor tyrosine kinases including MET, VEGF receptors, AXL, and RET. C has been approved in the US for the treatment of progressive, metastatic MTC and in the EU for progressive, unresectable locally advanced or metastatic MTC. In the phase 3 registrational study EXAM, pts were randomized 2:1 to receive 140 mg C or placebo (P) once daily (qd). The primary analysis for EXAM demonstrated a statistically significant improvement in progression-free survival (PFS) with a median PFS of 11.2 mo for C vs 4.0 mo for P (hazard ratio [HR] 0.28, 95% CI, 0.19–0.40; p < 0.001) (Elisei, JCO 2013). Dose reductions occurred commonly in the C arm with 82% of pts experiencing at least one dose reduction. While overall survival (OS) was not significantly improved in the overall population (median OS of 26.6 mo for C vs 21.1 mo for P; HR 0.85, 95% CI 0.64–1.12; p = 0.24), median OS was 44.3 mo for C vs 18.9 mo for P (HR 0.60, 95% CI 0.38–0.94) in the RET M918T-positive subgroup (Schlumberger, Ann Oncol 2017).

Trial design

EXAMINER (NCT01896479) is a global, randomized, double-blind study comparing the safety and efficacy of C at 60 vs 140 mg qd in pts with progressive, metastatic MTC using a noninferiority study design. Approximately 188 pts will be randomized 1:1 to receive C at 140 mg qd as capsules or 60 mg qd as tablets in Europe, Asia, Canada, and other regions. Eligible pts must have measurable disease and documented progressive disease within 14 mo prior to enrollment. A recent tumor tissue sample to test for RET and RAS mutations or documentation of a RET or RAS mutation is required. Pts will be stratified based on RET M918T status. After randomization, pts will be treated until disease progression per RECIST 1.1 or intolerable toxicity. Tumor assessments will be performed every 12 weeks. PFS and objective response rate evaluated by independent review are the primary and secondary efficacy endpoints, respectively; safety and correlation of tumor mutation status with clinical response are additional endpoints. The EXAMINER study continues to enroll pts.

Clinical trial identification

NCT0189647.

Legal entity responsible for the study

Exelixis, Inc.

Funding

The study was supported by Exelixis, Inc.

Editorial Acknowledgement

Disclosure

J. Krajewska: Honoraria and subinvestigator in clinical trials: Eisai, Exelixis, Sanofi-Genzyme, Bayer Health Care; Travel, accommodations, expenses: Sanofi-Genzyme, Ipsen, Novartis. B.G. Robinson: Stock or other ownership: Cochlear Ltd.; Honoraria, consulting or advisory role, speakers' bureau: Eisai; Travel, accommodations, expenses: Loxo. H. Gan: Consulting or advisory role: MSD, AbbVie; Speakers' bureau, travel, accommodations, expenses: Ignyta; Research funding: BMS, Ignyta. R. Elisei: Consulting or advisory role: Sanofi-Genzyme, Eisai, Loxo, Exelixis; Speakers' bureau: Sanofi-Genzyme, Eisai; Travel, accommodations, expenses: Sanofi-Genzyme. J. Partyka: Employment, research funding, travel, accommodations and expenses, stock or other ownership: Exelixis. A.E. Borgman: Employee, stock or other ownership: Exelixis. M. Schlumberger: Honoraria, research funding: Bayer, Eisai, Exelixis-Ipsen, Sanofi-Genzyme; Consulting or advisory role: Bayer, Eisai, Exelixis-Ipsen, Sanofi-Genzyme; Travel, accommodations, expenses: Bayer, Eisai, Sanofi-Genzyme. All other authors have declared no conflicts of interest.