@article{0813b207bf1042dfb612b3356ad26855,
title = "Overall survival analysis of EXAM, a phase III trial of cabozantinib in patients with radiographically progressive medullary thyroid carcinoma",
abstract = "Background: Primary analysis of the double-blind, phase III Efficacy of XL184 (Cabozantinib) in Advanced Medullary Thyroid Cancer (EXAM) trial demonstrated significant improvement in progression-free survival with cabozantinib versus placebo in patients with progressive medullary thyroid cancer (MTC). Final analysis of overall survival (OS), a key secondary endpoint, was carried out after long-term follow-up. Patients and methods: EXAM compared cabozantinib with placebo in 330 patients with documented radiographic progression of metastatic MTC. Patients were randomized (2:1) to cabozantinib (140 mg/day) or placebo. Final OS and updated safety data are reported. Results: Minimum follow-up was 42 months. Kaplan-Meier analysis showed a 5.5-month increase in median OS with cabozantinib versus placebo (26.6 versus 21.1 months) although the difference did not reach statistical significance [stratified hazard ratio (HR), 0.85; 95% confidence interval (CI), 0.64-1.12; P=0.24]. In an exploratory assessment of OS, progression-free survival, and objective response rate, cabozantinib appeared to have a larger treatment effect in patients with RET M918T mutation-positive tumors compared with patients not harboring this mutation. For patients with RET M918T-positive disease, median OS was 44.3 months for cabozantinib versus 18.9 months for placebo [HR, 0.60; 95% CI, 0.38-0.94; P=0.03 (not adjusted for multiple subgroup analyses)], with corresponding values of 20.2 versus 21.5 months (HR, 1.12; 95% CI, 0.70-1.82; P=0.63) in the RET M918T-negative subgroup. Median treatment duration was 10.8 months with cabozantinib and 3.4 months with placebo. The safety profile for cabozantinib remained consistent with that of the primary analysis. Conclusion: The secondary end point was not met in this final OS analysis from the trial of cabozantinib in patients with metastatic, radiographically progressive MTC. A statistically nonsignificant increase in OS was observed for cabozantinib compared with placebo. Exploratory analyses suggest that patients with RET M918T-positive tumors may experience a greater treatment benefit with cabozantinib.",
keywords = "Cabozantinib, Medullary thyroid cancer, Overall survival, Progression-free survival, RET M918T",
author = "M. Schlumberger and R. Elisei and S. M{\"u}ller and P. Sch{\"o}ffski and M. Brose and M. Shah and L. Licitra and J. Krajewska and Kreissl, {M. C.} and B. Niederle and Cohen, {E. E.W.} and L. Wirth and H. Ali and Clary, {D. O.} and Y. Yaron and M. Mangeshkar and D. Ball and B. Nelkin and S. Sherman",
note = "Funding Information: Exelixis, Inc (no grant numbers apply). Funding Information: MS received grant support from Exelixis, Inc., and has also received grant support, personal fees, and non-financial support from AstraZeneca, Sanofi-Genzyme, Bayer, and Eisai. RE consulted for Exelixis, Inc., Bayer, Genzyme, AstraZeneca, Eisai, and Bristol-Myers Squibb. Served on speaker bureaus for Exelixis, Inc., Bayer, Genzyme, and AstraZeneca. SM received travel-related financial support from Exelixis, Inc. PS is a lead investigator on Exelixis, Inc., clinical trials, consulted for Exelixis, Inc., and received financial support for advisory functions, educational activities, and related travel. MB received grant support and personal fees from Exelixis, Inc., AstraZeneca, and Genzyme. MS received grant support and personal fees from Exelixis, Inc. LL consulted for Eisai, Bristol-Myers Squibb, Merck Sharp & Dohme, Corp., Merck Serono, Boehringer Ingelheim, Debiopharm Group, Sobi, Novartis, AstraZeneca, Bayer, Roche, and Amgen, received research grant support from Eisai, Merck Sharp & Dohme, Corp., Merck Serono, Boehringer Ingelheim, Novartis, AstraZeneca, and Roche, and has received travel-related financial support from Merck Sorono, Debiopharm Group, Sobi, Bayer, and Amgen. JK is a member of Bayer Health Care Advisory Board, and received honoraria from AstraZeneca, Eisai, Exelixis, Inc., Ipsen, Novartis, Oxigene, Sanofi-Genzyme, and Sobi. MK received non-financial support from Exelixis, Inc., and he has also received personal fees and non-financial support from Sobi, Sanofi, and Eisai. AstraZeneca and Bayer have provided grant support, personal fees, and non-financial support. BN received personal fees from Exelixis, Inc. EC received speaking and consulting fees from Eisai and serves on advisory boards for Pfizer, Merck, AstraZeneca, and Bristol-Myers Squibb. LW received personal fees from Amgen, Blueprint, Eisai, Loxo, and Merck. DC is an employee and stock holder of Exelixis, Inc., and receives shared royalties from UCSF patent. YY and MM are employees and stock holders of Exelixis, Inc. DB received grant support from Exelixis, Inc. SS has received personal fees from Eisai, Bristol-Myers Squibb, Loxo, and Onyx. All remaining authors have declared no conflicts of interest. Publisher Copyright: {\textcopyright} The Author 2017. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved.",
year = "2017",
month = nov,
doi = "10.1093/annonc/mdx479",
language = "English (US)",
volume = "28",
pages = "2813--2819",
journal = "Annals of Oncology",
issn = "0923-7534",
publisher = "Oxford University Press",
number = "11",
}