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

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

Eur J Endocrinol. 2017 Jul 07;:

Authors: Capdevila J, Trigo JM, Aller J, Manzano JL, Garcia-Adrian S, Zafon C, Reig O, Bohn U, Ramon Y Cajal T, Duran M, Gonzalez-Astorga B, Lopez-Alfonso A, Medina J, Porras I, Reina JJ, Palacios N, Grande E, Cillan E, Matos I, Grau JJ

Abstract
BACKGROUND: Axitinib, an antiangiogenic multikinase inhibitor (MKI) was evaluated in the compassionate-use-program in Spain (October 2012-November 2014).
MATERIALS AND METHODS: 47 patients with advanced radioactive iodine-refractory differentiated thyroid cancer (DTC, n=34) or medullary thyroid cancer (MTC, n=13) with documented disease progression were treated with axitinib 5 mg bid. The primary efficacy endpoint was overall response rate (ORR) by RECIST v1.1. Progression-free survival (PFS) and adverse events (AEs) were secondary objectives. Regulatory authorities validated the CUP and all patients signed informed consent form.
RESULTS: Axitinib was administered as first-line therapy in 17 patients (36.2%), as second-line in 18 patients (38.3%) and as third/fourth-line in 12 patients (25.5%). With a median follow-up of 11.5 months (0-24.3), ORR was 27.7% (DTC: 29.4% and MTC: 23.1%), median PFS was 8.1 months (95%CI 4.1-12.2); (DTC: 7.4 months [95%CI 3.1-11.8] and MTC: 9.4 months [95%CI 4.8-13.9]). Better outcomes were reported with first-line axitinib, with an ORR of 53% and a median PFS of 13.6 months compared with 16.7% and 10.6 months as second-line treatment. Twelve (25.5%) patients required dose reduction to 3 mg bid. All-grade AEs included asthenia (53.2%), diarrhoea (36.2%), hypertension (31.9%), mucositis (29.8%); grade 3/4 AEs included anorexia (6.4%), diarrhoea (4.3%), cardiac toxicity (4.3%).
CONCLUSION: Axitinib had a tolerable safety profile and clinically meaningful activity in refractory and progressive thyroid cancer regardless of histology as first-line therapy. To our knowledge, this is the first time that cross-resistance between MKIs is suggested in thyroid cancer, highlighting the importance of prospective sequential clinical studies.

PMID: 28687563 [PubMed - as supplied by publisher]

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