Safety of denosumab in patients with refractory differentiated thyroid cancer and advanced medullary thyroid cancer.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e17578-e17578 ◽  
Author(s):  
Johanna Wassermann ◽  
Elise Mathy ◽  
Geraldine Lescaille ◽  
Marine Slim ◽  
Camille Buffet ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Bone Metastases ◽  
Differentiated Thyroid Cancer ◽  
Medullary Thyroid Cancer ◽  
Kinase Inhibitor ◽  
Calcium Supplementation ◽  
Osteonecrosis Of The Jaw ◽  
Treatment Benefit ◽  
Medullary Thyroid ◽  
Cervical Surgery

e17578 Background: Few data exist regarding the use of denosumab in patients with bone metastases from radioactive iodine (RAI) refractory differentiated thyroid cancer (DTC) and advanced medullary thyroid cancer (MTC). We aimed to describe adverse events of specific interest - osteonecrosis of the jaw (ONJ) and severe hypocalcemia - in this rare setting. Methods: We retrospectively reviewed the charts of all the patients treated with denosumab for bone metastases from RAI-refractory DTC and advanced MTC in our institution. All patients had a calcium measurement and a clinical and radiological dental screening before denosumab initiation. All patients without hypercalcemia received a calcium supplementation. We assessed associations between ONJ or severe hypocalcemia ( < 1.75mmol/L) and suspected risk factors by Fisher exact tests. Results: Between 2014 and 2018, 23 patients were treated with denosumab. Two-thirds of patients were male (n = 16), median age was 69 years (range 43-87). Histology was DTC and MTC in 19 (83%) and 4 (17%) patients, respectively. DTC patients had received a median cumulated dose (CD) of 300 mCi of RAI (range 100-700). Ten patients (43%) had at least one cervical surgery for recurrence or persistence, and 6 (26%) had cervical radiotherapy. Four patients had hypoparathyroidism before denosumab initiation. Two-thirds of patients ( n =15) received a tyrosine kinase inhibitor (TKI) in association with denosumab. The median duration of denosumab was 20 months (range 1-47). ONJ occurred in 6 patients (26%) and severe hypocalcemia in 3 patients (13%). Conclusions: Patients with RAI-refractory DTC and advanced MTC are at high risk of ONJ and severe hypocalcemia under denosumab treatment. Benefit/risk ratio should be highly weighted particularly when treatment is prolonged. Patients should be closely monitored for the risk of ONJ and hypocalcemia. [Table: see text]

scholarly journals The RET Kinase Inhibitor NVP-AST487 Blocks Growth and Calcitonin Gene Expression through Distinct Mechanisms in Medullary Thyroid Cancer Cells

2007 ◽  
Vol 67 (14) ◽  
pp. 6956-6964 ◽  
Author(s):  
Nagako Akeno-Stuart ◽  
Michelle Croyle ◽  
Jeffrey A. Knauf ◽  
Roberta Malaguarnera ◽  
Donata Vitagliano ◽  
...  
Keyword(s):  
Gene Expression ◽  
Thyroid Cancer ◽  
Cancer Cells ◽  
Medullary Thyroid Cancer ◽  
Kinase Inhibitor ◽  
Medullary Thyroid ◽  
Calcitonin Gene ◽  
Thyroid Cancer Cells

Efficacy of selpercatinib after prior systemic therapy in patients with RET mutant medullary thyroid cancer.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 6074-6074
Author(s):  
Lori J. Wirth ◽  
Eric Jeffrey Sherman ◽  
Daniela Weiler ◽  
Maria E. Cabanillas ◽  
Bruce Robinson ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Systemic Therapy ◽  
Medullary Thyroid Cancer ◽  
Kinase Inhibitor ◽  
Case Reports ◽  
Objective Response ◽  
Previous Response ◽  
Medullary Thyroid ◽  
Prior Therapy ◽  
Altered Thyroid

6074 Background: Selpercatinib is a first-in-class, CNS active, highly selective, and potent RET kinase inhibitor which has demonstrated durable antitumor activity in patients (pts) with RET altered thyroid cancer and is approved in multiple countries for the treatment of RET fusion+ lung or thyroid cancers. As response rates to cancer therapy usually decline on subsequent lines of therapy, the efficacy of selpercatinib was examined in the context of the last prior therapy received before trial enrollment. Methods: Pts with RET mutant medullary thyroid cancer (MTC) previously treated with multikinase inhibitors (cabozantinib and/or vandetanib) were enrolled in the global LIBRETTO-001 trial (NCT03157128). This post-hoc exploratory intrapatient analysis, based on March 30, 2020 data cutoff date, was performed to compare the retrospective physician-reported objective response rate (ORR) from the last systemic therapy prior to enrollment, as reported in pts case reports, to ORR by independent review committee per RECIST 1.1 with selpercatinib treatment, with each patient serving as his/her own control. Results: Efficacy-evaluable pts, 64% male, 90% white with a median age of 58 years, received prior therapy for MTC (n = 143). Pts had a median of 2 (range 1-8) prior systemic regimens. The ORR on selpercatinib (69%) was markedly higher than for the last prior therapy (10%) received before enrollment. ORR improvements with selpercatinib were observed regardless of prior therapy: cabozantinib (66% vs 14%) or vandetanib (71% vs 12%). Fewer pts had progressive disease as their best overall response with selpercatinib (2/143; 1.4%) compared to last prior therapy (33/143; 23.1%). Notably selpercatinib achieved 62% ORR in pts that did not respond to their previous line of therapy prior to enrolment. This shift from non-responder to responder on selpercatinib therapy was consistent regardless of prior cabozantinib or vandetanib treatment, where pts achieved 57% and 61% ORR respectively when subsequently treated with selpercatinib. In contrast, only 3% of patients did not respond to selpercatinib after a previous response to the immediate prior therapy. Similarly, 5% and 2% of patients were non-responders on selpercatinib after a prior response with cabozantinib and vandetanib therapy respectively. Conclusions: Prior to selpercatinib, response with previous multikinase therapy was rare. By contrast, selpercatinib demonstrated robust efficacy regardless of response to or specific prior therapy in pts with RET mutant MTC. Clinical trial information: NCT03157128.

Phase I trial of combination sorafenib and tipifarnib: The experience in advanced differentiated thyroid cancer (DTC) and medullary thyroid cancer (MTC).

2010 ◽  
Vol 28 (15_suppl) ◽  
pp. 5586-5586 ◽  
Author(s):  
M. E. Cabanillas ◽  
R. Kurzrock ◽  
S. I. Sherman ◽  
A. M. Tsimberidou ◽  
S. Waguespack ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Phase I ◽  
Differentiated Thyroid Cancer ◽  
Phase I Trial ◽  
Medullary Thyroid Cancer ◽  
Medullary Thyroid

scholarly journals Vandetanib (ZD6474) in the Treatment of Medullary Thyroid Cancer

2011 ◽  
Vol 5 ◽  
pp. CMO.S6197 ◽  
Author(s):  
Hari Deshpande ◽  
Sanziana Roman ◽  
Jaykumar Thumar ◽  
Julie Ann Sosa
Keyword(s):  
Thyroid Cancer ◽  
Growth Factor ◽  
Phase Ii ◽  
Medullary Thyroid Cancer ◽  
Kinase Inhibitor ◽  
Locally Advanced ◽  
Growth Factor Receptor ◽  
Good Choice ◽  
Phase Ii Trials ◽  
Medullary Thyroid

Vandetanib (ZD6474) is an orally bioavailable small molecule tyrosine kinase inhibitor of multiple growth factor receptors, including RET (Rearrange during transfection), vascular endothelial growth factor receptor-2 (VEGFR-2) and epidermal growth factor receptor (EGFR). The activity against RET and VEGF made it a good choice in the treatment of medullary thyroid cancer (MTC). As there is considerable cross talk between growth factor pathways, dual inhibition with such agents has become an attractive strategy, in the treatment of many malignancies with encouraging Phase II clinical trial data to date. Vandetanib was tested in two Phase II trials in the treatment of patients with medullary thyroid cancer at doses of 100 mg and 300 mg daily respectively. The encouraging results of these 2 trials led to a randomized phase II trial comparing this medication to placebo using a crossover design. More than 300 patients were included in this study, which ultimately showed a significant improvement in progression-free survival in patients taking vandetanib. Based on these results, the Oncology Drug Advisory Committee (ODAC) of the Food and Drug Administration (FDA) recommended that vandetanib be approved for the treatment of patients with unresectable locally advanced or metastatic medullary thyroid cancer.

Serum Calcitonin May Falsely Estimate Tumor Burden in Chronic Hypercalcemia: A Case of Prostatic and Multiple Bone Metastases from Medullary Thyroid Cancer

Thyroid ◽  
2014 ◽  
Vol 24 (3) ◽  
pp. 599-603 ◽  
Author(s):  
Hee Kyung Kim ◽  
Woo Kyun Bae ◽  
Yoo Duk Choi ◽  
Hyun Jeong Shim ◽  
Jee Hee Yoon ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Bone Metastases ◽  
Medullary Thyroid Cancer ◽  
Tumor Burden ◽  
Serum Calcitonin ◽  
Medullary Thyroid ◽  
Multiple Bone Metastases

Axitinib treatment in advanced RAI-resistant differentiated thyroid cancer (DTC) and refractory medullary thyroid cancer (MTC).

2014 ◽  
Vol 32 (15_suppl) ◽  
pp. 6027-6027 ◽  
Author(s):  
Jaume Capdevila ◽  
Jose Manuel Trigo Perez ◽  
Javier Aller ◽  
Jose Luis Manzano ◽  
Silvia Garcia Adrian ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Differentiated Thyroid Cancer ◽  
Medullary Thyroid Cancer ◽  
Medullary Thyroid

External Beam and Nuclear Therapy of Medullary Thyroid Cancer

2021 ◽  
Vol 66 (1) ◽  
pp. 79-84
Author(s):  
I Pimonova ◽  
V. Krylov ◽  
P Isaev ◽  
T. Kochetova ◽  
E Borodavina
Keyword(s):  
Thyroid Cancer ◽  
Bone Metastases ◽  
Radionuclide Therapy ◽  
Medullary Thyroid Cancer ◽  
Combined Therapy ◽  
Somatostatin Analogs ◽  
Distant Metastases ◽  
Targeted Drugs ◽  
Medullary Thyroid ◽  
Peptide Receptor

The article reviews domestic and foreign literature on the use of radiation therapy in the treatment of medullary thyroid cancer. The possibilities of various radiation methods in the treatment of patients with distant metastases are shown. In addition to classical types of remote irradiation, data are presented on the possibilities of radionuclide therapy (peptide-receptor therapy with somatostatin analogs and radionuclide therapy with osteotropic drugs for bone metastases). Methods of combined therapy with the use of osteomodifying agents, targeted drugs and other methods are described, which make it possible to increase the effectiveness of treatment of patients with medullary thyroid cancer with bone metastases.

scholarly journals Comparison of 68Ga PET/CT to Other Imaging Studies in Medullary Thyroid Cancer: Superiority in Detecting Bone Metastases

2018 ◽  
Vol 103 (9) ◽  
pp. 3250-3259 ◽  
Author(s):  
Luciana Audi Castroneves ◽  
George Coura Filho ◽  
Ricardo Miguel Costa de Freitas ◽  
Raphael Salles ◽  
Raquel Ajub Moyses ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Bone Metastases ◽  
Medullary Thyroid Cancer ◽  
Imaging Studies ◽  
Medullary Thyroid ◽  
Pet Ct
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