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Targeted Oncology
Published in: Targeted Oncology 6/2019

01-12-2019 | Regorafenib | Original Research Article

Regorafenib-Induced Hypothyroidism as a Predictive Marker for Improved Survival in Metastatic or Unresectable Colorectal Cancer Refractory to Standard Therapies: A Prospective Single-Center Study

Authors: Jwa Hoon Kim, Sun Young Kim, Kyu-pyo Kim, Tae Won Kim, Sun Young Chae, Hwa Jung Kim, Jae Seung Kim, Jin-Sook Ryu, Dae Hyuk Moon, Jeong Eun Kim, Yong Sang Hong

Published in: Targeted Oncology | Issue 6/2019

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Abstract

Background

Tyrosine kinase inhibitor-induced hypothyroidism is associated with favorable survival in patients with various cancers.

Objective

We aimed to investigate the incidence of regorafenib-induced hypothyroidism and assess its prognostic value in patients with metastatic or unresectable colorectal cancer (CRC) receiving regorafenib.

Patients and Methods

This study included 68 patients treated at Asan Medical Center (Seoul, Republic of Korea) between 2014 and 2016 with metastatic or unresectable CRC refractory to standard therapies. Regorafenib (160 mg/day on days 1–21 followed by a 7-day break) was administered.

Results

The median patient age was 58 (range 26–72) years; 61.8% of patients were male. Among the 68 patients, 50 (73.5%) showed hypothyroidism; 39 (57.4%) had subclinical and 11 (16.2%) had symptomatic hypothyroidism. Overall, the objective response rate (ORR) and disease control rate (DCR) were 7.4% and 70.6%, respectively; both were significantly higher in patients with symptomatic or subclinical hypothyroidism than in euthyroid patients (ORR 27.3% vs. 5.1% vs. 0.0%, P = 0.001; DCR 100% vs. 76.9% vs. 38.9%, P = 0.001). Median progression-free survival (PFS) and overall survival (OS) were longer in patients with symptomatic hypothyroidism than in those with subclinical hypothyroidism (median PFS 9.1 vs. 3.8 months, P = 0.018; median OS: 19.2 vs. 9.4 months, P = 0.012) or with euthyroid status (median PFS 9.1 vs. 1.8 months, P < 0.001; median OS 19.2 vs. 4.7 months, P = 0.001). Symptomatic hypothyroidism was a significant protective factor for PFS (hazard ratio (HR) = 0.37, P = 0.006) and OS (HR = 0.35, P = 0.007); no other adverse events were associated with survival.

Conclusions

Regorafenib-induced hypothyroidism frequently occurs in patients with metastatic CRC receiving regorafenib and is associated with improved survival. Thyroid function status should be actively monitored in CRC patients receiving regorafenib.
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Metadata
Title
Regorafenib-Induced Hypothyroidism as a Predictive Marker for Improved Survival in Metastatic or Unresectable Colorectal Cancer Refractory to Standard Therapies: A Prospective Single-Center Study
Authors
Jwa Hoon Kim
Sun Young Kim
Kyu-pyo Kim
Tae Won Kim
Sun Young Chae
Hwa Jung Kim
Jae Seung Kim
Jin-Sook Ryu
Dae Hyuk Moon
Jeong Eun Kim
Yong Sang Hong
Publication date
01-12-2019
Publisher
Springer International Publishing
Published in
Targeted Oncology / Issue 6/2019
Print ISSN: 1776-2596
Electronic ISSN: 1776-260X
DOI
https://doi.org/10.1007/s11523-019-00672-2

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