Targeted Oncology

, Volume 14, Issue 6, pp 689–697 | Cite as

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

  • 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 KimEmail author
  • Yong Sang HongEmail author
Original Research Article



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


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.


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.


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.



Regorafenib was kindly provided by Bayer.

Compliance with Ethical Standards


This study was funded by a Grant (2014-9079) from the Asan Institute for Life Sciences, Asan Medical Center, Seoul, Korea; a Grant from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health and Welfare, Republic of Korea (Grant number HI18C2383); and 2017 cancer research support project of the Korea Foundation for Cancer Research (CB-2017-B-2).

Conflict of interest

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, and Yong Sang Hong declare that they have no conflicts of interest that might be relevant to the contents of this manuscript.


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Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Jwa Hoon Kim
    • 1
  • Sun Young Kim
    • 1
  • Kyu-pyo Kim
    • 1
  • Tae Won Kim
    • 1
  • Sun Young Chae
    • 2
  • Hwa Jung Kim
    • 3
  • Jae Seung Kim
    • 2
  • Jin-Sook Ryu
    • 2
  • Dae Hyuk Moon
    • 2
  • Jeong Eun Kim
    • 1
    Email author
  • Yong Sang Hong
    • 1
    Email author
  1. 1.Department of Oncology, Asan Medical CenterUniversity of Ulsan College of MedicineSeoulRepublic of Korea
  2. 2.Department of Nuclear Medicine, Asan Medical CenterUniversity of Ulsan College of MedicineSeoulRepublic of Korea
  3. 3.Department of Preventive Medicine, Asan Medical CenterUniversity of Ulsan College of MedicineSeoulRepublic of Korea

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