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Cabozantinib; Medullary thyroid cancer; Tyrosine kinase inhibitor Cabozantinib; Càncer medul·lar de tiroides; Inhibidor de la tirosina cinasa Cabozantinib; Cáncer medular de tiroides; Inhibidor de la tirosina cinasa Background: Cabozantinib inhibits pathways involved in medullary thyroid cancer (MTC). Cabozantinib is approved as 140 mg/day in capsules for MTC and 60 mg/day in tablets for other solid tumors. This study compared the two doses in progressive metastatic MTC. Methods: In this Phase 4, randomized, double-blind noninferiority (NI) trial (NCT01896479), patients with progressive metastatic MTC were randomized 1:1 to cabozantinib 60 mg/day tablet or 140 mg/day capsules. The primary end point was progression-free survival (PFS) by blinded independent radiology committee (BIRC) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. NI would be concluded if the upper 95% confidence interval [CI] for the PFS hazard ratio (HR) was less than the NI margin, 1.58. The secondary end point was objective response rate (ORR) by BIRC per RECIST v1.1; additional end points included safety and pharmacokinetics. Results: At data cutoff (July 15, 2020), 247 patients were randomized to the 60 mg/day tablet arm (n = 123) and the 140 mg/day capsules arm (n = 124). NI was not met (median PFS 11.0 months vs. 13.9 months in the 60 and 140 mg/day arms [HR 1.24; CI 0.90–1.70; p = 0.19]). The ORR was 33% in both arms. Generally, adverse event (AE) incidence was lower in the 60 mg/day arm (Grade 3/4, 63% vs. 72%), as were dose reductions (69% vs. 81%) and treatment discontinuations due to AEs (23% vs. 36%). Initially, cabozantinib plasma concentrations were higher in the 140 mg/day arm but became similar between arms at later time points. Conclusions: PFS NI of the cabozantinib 60 mg/day tablet vs. 140 mg/day capsules was not met. The 60 mg/day tablet had the same ORR and lower rates of AEs. This work was supported by Exelixis, Inc., Alameda, CA, USA (no grant number). Exelixis was involved in the study design, the collection, analysis, and interpretation of data, the writing of the report, and the decision to submit for publication.

Struma ovarii is a rare variant of the mature ovarian teratoma composed of more than 50% thyroid tissue. Thyroid type carcinoma can occur in 5% of struma ovarii. Given the rarity of this pathology, as well as the different clinical course, approaches to the treatment of this disease are controversial. The proposed approaches to treatment vary from ovarian resection to total hysterectomy with bilateral salpingo-oophorectomy and adjuvant therapy. We present here 6 case reports of thyroid type carcinoma in struma ovarii and outcome of patients treated in our clinic. All patients had pelvic surgery of different extent, followed by thyroidectomy and radioiodine therapy. The incidence of metastasis is 67% (4/6), 2 - intraperitoneal metas-tases, 2 - bone metastases. Among patients with metastases, 2 have reached a complete response, one with a good response continues treatment, one had progression. The follow-up period is 1 to 15 years (median 4 years). One patient with follicular carcinoma died of progression 8 years after diagnosis. The remaining patients are alive.

We evaluated the results of treatment of 215 pediatric patients with papillary thyroid carcinoma (PTC). Median age at diagnosis was 14 (5 - 18 y.o). Thyroidectomy performed in 105, subtotalthyroidectomy in 8, lobectomy - in 102, additional lymph node dissection - in 169, radioiodine ablation/ therapy - in 102 patients. Follicular variant PTC was found in 41 (19%), solid - in 37 (17%), diffuse sclerosing - in 3 (1%), the remaining had a classical PTC with mainly papillary (90; 42%) or follicular (44; 21%) pattern. 21% had multifocal PTC, 4,6% - extrathyroidal extension, 62% - regional lymph node metastases, 12% - lung metastases. The follow up was 95 months (6 - 301 mo). All patients are alive. Recurrence of PTC occurred in 37 (17%): 7 - thyroid remnant, 26 - cervical lymph nodes, 4 - distant lung metastases. Prognostic factors for distant metastases were young age at diagnosis

e17518 Background:Long time the patients with high-differentiated thyroid cancer with distant metastases had only one type of treatment. It was radioiodine therapy courses and follow-up. In cases of revealed radioiodine (RAI) refractory process we did not have possibilities for treatment this category of patients. Results of trials DECISION and SELECT gave to oncologist new keys for successful treatment. We present our group of RAI refractory thyroid cancer patients, which was treated by Lenvatinib like routine clinical practice. Methods:We have on treatment 8 patients (3-male, 5-female). Histologically – papillary thyroid carcinoma. Provisions of national clinical recommendations were considered as criteria of a RAI-refractory status. Existence of a symptomatic progression of a tumor was main criterion. Results:Six patients received from 7 to 14 month courses of treatment. All these patients are revealed partial response of the tumor lesions by PET-FDG-CT and the dramatically decrease of thyroglobulin level is noted. Two patients stopped treatment after 1 month of therapy. One patient due to destructive pneumonia, other patient – death due to myocardial infarction. Adverse events not related with Lenvatinib. The adverse events were controllable. We noted the expressed arterial hypertension. Before correction of a dose of a drug increase of arterial pressure more than 160/100 mm Hg is noted. Arterial pressure managed to be corrected the combined scheme of therapy (amlodipin, bisoprolol, hydrochlorthiazide). Correction of a dose of lenvatinib is made at 3 patients to 20 mg daily, 2 patient – 14. Conclusions:Introduction of a lenvatinib clinical practice is very successful. But we noted of important accurate expert selection of patients for treatment after establishment of a condition of a RAI-refractory and revealed really symptomatic progression, adequate correction of the adverse effects (arterial hypertension) and well-timed correction of a dose of a lenvatinib.