Long-term analysis of the efficacy and tolerability of sorafenib in advanced radio-iodine refractory differentiated thyroid carcinoma: final results of a phase II trial

Schneider, Tatiana; Abdulrahman, Randa M.; Corssmit, Eleonora P M; Morreau, Hans; Smit, Johannes; Kapiteijn, Ellen

doi:10.1530/eje-12-0405

Cited by 120 publications

(133 citation statements)

References 25 publications

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“…Palmar-plantar erythrodysesthesia was the most common AE, occurring in 87.5% patients and reaching grade 3 in 37.5% of the patients, followed by alopecia, hypertension, diarrhea, fatigue and weight loss. These results were similar to those reported by other phase II clinical trials of sorafenib in thyroid cancer (11,13,18). Notably, 1 patient developed grade 4 hypocalcemia on sorafenib, despite daily intravenous calcium supplementation, and another patient experienced a grade 4 amylase level elevation and grade 3 weight loss and fatigue.…”

Section: Grade 1 Grade 2 Grade 3 Grade 4 ----------------------------supporting

confidence: 89%

“…The majority of the patients (87.5%) had developed lung metastases, which responded better to sorafenib compared to other organ lesions. However, inconsistent with the response rate, the PFS and OS were shorter compared to those observed in other phase II trials (10,11,18). This difference may be attributed to the dose reduction due to the development of AEs, with 2 of the 3 patients who underwent a reduction in the dose of sorafenib to <400 mg̸day experiencing disease progression and eventually succumbing to the disease.…”

Section: Grade 1 Grade 2 Grade 3 Grade 4 ----------------------------mentioning

confidence: 61%

“…The median PFS and OS were 40.1 and 55.0 weeks, respectively. The PR rate appeared to be superior compared to that in published phase II trials evaluating sorafenib in DTC (10)(11)(12)18). These differences in response may simply reflect the pre-study characteristics of our patient group.…”

Section: Grade 1 Grade 2 Grade 3 Grade 4 ----------------------------mentioning

confidence: 64%

“…Two phase II clinical trials of sorafenib reported an efficacy of this drug in metastatic DTC. In a study by Schneider et al (18), 31 patients with progressive, metastatic or locally advanced RAI-refractory DTC received sorafenib. After a median follow-up of 25 months, the response rates were 31% PR and 42% SD, the median PFS was 18 months and the median OS 34.5 months.…”

Section: Discussionmentioning

confidence: 99%

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Sorafenib in metastatic radioactive iodine-refractory differentiated thyroid cancer: A pilot study

Luo

Shi

Xing

et al. 2013

Molecular and Clinical Oncology

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Abstract. The incidence and mortality of thyroid cancer are on the increase worldwide and the treatment options for progressive, radioactive iodine (RAI)-refractory metastatic differentiated thyroid cancer (DTC) patients are currently limited. Sorafenib is a multikinase inhibitor that targets several molecular signals, which are believed to be involved in the pathogenesis of DTC. In this study, we reported our experience with the off-label use of sorafenib in Chinese cancer patients. A total of 8 patients (7 with papillary and 1 with follicular thyroid cancer) were recruited in this study. The partial response (PR) rate was 50.0% and 5 of the 8 patients (62.5%) achieved a durable response. The median progression-free survival (PFS) and overall survival (OS) were 40.1 and 55.0 weeks, respectively. Lung metastases were more sensitive to sorafenib compared to lymph nodes. The tumor marker response was not in accordance with the radiological response, although patients with tumor marker complete response (CR) exhibited a longer PFS and OS compared to those without a CR. Common adverse events (AEs) included palmar-plantar erythrodysesthesia, hypertension, diarrhea, weight loss and alopecia. Grade 4 AEs comprised hypocalcemia (1 patient) and elevated amylase levels (1 patient). A dose reduction was required in 62.5% of the patients. In conclusion, sorafenib exhibited a clinically relevant antitumor activity in patients with progressive metastatic RAI-refractory DTC, although the majority of the patients required a dose reduction due to intolerable toxicity. IntroductionThe incidence and mortality of thyroid cancer are increasing worldwide. Differentiated thyroid cancer (DTC), namely papillary thyroid carcinoma (PTC) and follicular thyroid carcinoma (FTC), comprise ~94% of these cases (1). Despite the majority of the DTC patients having indolent disease, ~5-10% of these patients will eventually develop metastatic disease, no longer responding to radioiodine (RAI) therapy or thyroid-stimulating hormone (TSH) suppression and exhibiting a more aggressive course and short survival (2-4). Doxorubicin is the only currently available treatment option that has been approved by the Food and Drug Administration (FDA) for such patients, with a progression-free survival (PFS) of only 2 months and a median overall survival (OS) of 8 months; however, it is accompanied by severe myelosuppression and cumulative cardiotoxicity (5). Therefore, RAI-refractory DTC is a disease requiring novel therapeutic options exhibiting better efficacy and less toxicity.Activating mutations in certain genes were previously reported to play a critical role in the development of DTC and the majority of DTCs may be due to single activating somatic mutations in one of three genes: BRAF mutations, RET̸PTC rearrangements and Ras mutations (6-9). Sorafenib is a small-molecule multikinase inhibitor that targets several molecular signals which have been proven as potential therapeutic targets in DTC. Four phase II trials using sorafenib for metastatic thyroid c...

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Section: Grade 1 Grade 2 Grade 3 Grade 4 ----------------------------supporting

confidence: 89%

Section: Grade 1 Grade 2 Grade 3 Grade 4 ----------------------------mentioning

confidence: 61%

Section: Grade 1 Grade 2 Grade 3 Grade 4 ----------------------------mentioning

confidence: 64%

Section: Discussionmentioning

confidence: 99%

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Sorafenib in metastatic radioactive iodine-refractory differentiated thyroid cancer: A pilot study

Luo

Shi

Xing

et al. 2013

Molecular and Clinical Oncology

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“…Our study results might also be pertinent to therapeutic decision-making. There is growing evidence that BRAF mutation-targeted therapy (sorafenib) is effective in metastatic or advanced thyroid cancer [26][27][28]. There was also a report that in iodine-refractory differentiated thyroid cancer, an early 18 F-FDG PET response was useful for identifying sorafenib non-responders, although no BRAF mutation analysis was performed in those patients [29].…”

Section: Discussionmentioning

confidence: 99%

Association Between 18F-FDG Avidity and the BRAF Mutation in Papillary Thyroid Carcinoma

Lee

Han

Lee

et al. 2015

Nucl Med Mol Imaging

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Purpose The BRAF mutation, a potential prognostic factor in papillary thyroid carcinoma (PTC), is associated with a high expression of the glucose transporter gene. We investigated which clinicopathologic factors, including BRAF mutation status, influence 18 F-fluoro-2-deoxyglucose ( 18 F-FDG) avidity. Methods We retrospectively reviewed 55 patients who underwent BRAF analysis from biopsy-confirmed PTC and 18 F-FDG positron emission tomography/computed tomography within 6 months before undergoing thyroid surgery from September 2008 to August 2014. Tumors were considered to be 18 F-FDG avid if the uptake was greater than that of the liver. 18 F-FDG uptake of PTCs was also analyzed semiquantitatively using SUV max . The association between 18 F-FDG avidity and clinicopathologic variables (age, tumor size, perithyroidal extension, cervical lymph node status, and BRAF mutation status) was investigated. Results Twenty-nine (52.7 %) of 55 patients had 18 F-FDGavid PTCs. PTCs with the BRAF mutation showed higher 18 F-FDG avidity (24/38, 63.2 %) than those without (5/17, 29.4 %). The BRAF mutation (p=0.025) and tumor size (p= 0.003) were significantly associated with 18 F-FDG avidity in univariate analysis, and the BRAF mutation status remained significant after adjusting for tumor size in multivariate analysis (p=0.015). In the subgroup of tumor size≥1 cm, the BRAF mutation was the only factor significantly associated with 18 F-FDG avidity (p=0.021). The mean SUV max of PTCs with the BRAF mutation was significantly higher than that of those without (4.89±6.12 vs. 1.96±1.10, p=0.039). Conclusions The BRAF mutation must be one of the most important factors influencing 18 F-FDG avidity in PTCs, especially in those with a tumor size≥1 cm.

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Efficacy and safety of pembrolizumab monotherapy in patients with advanced thyroid cancer in the phase 2 KEYNOTE‐158 study

Algazi

Capdevila

et al. 2023

Cancer

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Background:The authors report results from the thyroid carcinoma cohort of the multicohort phase 2 KEYNOTE-158 study (NCT02628067), which evaluated pembrolizumab monotherapy in patients with previously treated cancers.Methods: Eligible patients had histologically and/or cytologically confirmed papillary or follicular thyroid carcinoma, failure of or intolerance to prior therapy, and measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.Patients received pembrolizumab (200 mg) every 3 weeks for up to 35 cycles. The primary end point was objective response rate (ORR) per RECIST v1.1 by independent central review.Results: A total of 103 patients were enrolled and received pembrolizumab. Median duration from first dose to data cutoff (October 5, 2020) was 49.4 (range, 43.9-54.9) months. ORR was 6.8% (95% confidence interval [CI], 2.8%-13.5%), and median duration of response was 18.4 (range, 4.2-47.2+) months. ORR was 8.7% (95% CI, 2.4%-20.8%) among patients with programmed cell death ligand 1 (PD-L1) combined positive score (CPS) ≥1 (n = 46) and 5.7% (95% CI, 1.2%-15.7%) among patients with PD-L1 CPS <1 (n = 53). Median overall survival and progression-free survival were 34.5 (95% CI, 21.2 to not reached) and 4.2 (95% CI, 3.9-6.2) months, respectively. Treatment-related adverse events occurred in 69.9% of patients (grade 3-5, 14.6%).Conclusions: Pembrolizumab demonstrated manageable toxicity and durable antitumor activity in a small subset of patients with advanced thyroid cancer. TheseThe trial registration is ClinicalTrials.gov, NCT02628067.

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Long-term analysis of the efficacy and tolerability of sorafenib in advanced radio-iodine refractory differentiated thyroid carcinoma: final results of a phase II trial

Cited by 120 publications

References 25 publications

Sorafenib in metastatic radioactive iodine-refractory differentiated thyroid cancer: A pilot study

Sorafenib in metastatic radioactive iodine-refractory differentiated thyroid cancer: A pilot study

Association Between 18F-FDG Avidity and the BRAF Mutation in Papillary Thyroid Carcinoma

Efficacy and safety of pembrolizumab monotherapy in patients with advanced thyroid cancer in the phase 2 KEYNOTE‐158 study

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