A multicenter, phase II trial of everolimus in locally advanced or metastatic thyroid cancer of all histologic subtypes.
BACKGROUND
This phase II study investigated the efficacy and safety of everolimus, an inhibitor of mammalian target of rapamycin (mTOR), in locally advanced or metastatic thyroid cancer.


METHODS
Patients with thyroid cancer of any histology that was resistant or not appropriate for (131)I received everolimus 10 mg daily orally until unacceptable toxicity or disease progression. The primary end point was disease control rate [partial response (PR) + stable response ≥12 weeks]. Secondary end points included response rates, clinical benefit (PD + durable stable disease (SD)], progression-free survival (PFS), overall survival, duration of response, and safety.


RESULTS
Thirty-eight of 40 enrolled patients were evaluable for efficacy. The disease control rate was 81% and two (5%) patients achieved objective response; their duration of response was 21+ and 24+ weeks. Stable disease (SD) and progressive disease was reported in 76% and 17% of patients, respectively. Seventeen (45%) patients showed durable SD (≥24 weeks) and clinical benefit was reported in 19 (50%) patients. Median PFS was 47 weeks [95% confidence interval (CI) 14.9-78.5]. Calcitonin, CEA, and thyroglobulin concentrations were ≥50% lower than baseline in three (30%) and four (44%) patients with medullary thyroid cancer and five (33%) patients with PTC, respectively. The most common treatment-related adverse events were mucositis (84%), anorexia (44%), and aspartate transaminase/alanine transaminase elevation (26%).


CONCLUSIONS
Everolimus had a limited activity with low response rate in locally advanced or metastatic thyroid cancer. Reasonable clinical benefit rate and safety profile may warrant further investigation.
NCT01164176.
Department of Internal Medicine, Division of Medical Oncology, Yonsei University College of Medicine, Seoul.
S M
SM
Lim
H
H
Chang
M J
MJ
Yoon
Y K
YK
Hong
H
H
Kim
W Y
WY
Chung
C S
CS
Park
K H
KH
Nam
S W
SW
Kang
M K
MK
Kim
S B
SB
Kim
S H
SH
Lee
H G
HG
Kim
I I
II
Na
Y S
YS
Kim
M Y
MY
Choi
J G
JG
Kim
K U
KU
Park
H J
HJ
Yun
J H
JH
Kim
B C
BC
Cho
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D018276:Carcinoma, Medullary / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary; D002291:Carcinoma, Papillary / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary; D018572:Disease-Free Survival; D000068338:Everolimus; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D020123:Sirolimus / Q000031:analogs & derivatives* / Q000627:therapeutic use; D013964:Thyroid Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D000068338:Everolimus; D020123:Sirolimus
efficacy; everolimus; mTOR inhibitor; safety; thyroid cancer