RT Journal Article
T1 Axitinib treatment in advanced RAI-resistant differentiated thyroid cancer (DTC) and refractory medullary thyroid cancer (MTC).
A1 Capdevila, Jaume
A1 Trigo, José Manuel
A1 Aller, Javier
A1 Manzano, José Luís
A1 Adrián, Silvia García
A1 Llopis, Carles Zafón
A1 Reig, Òscar
A1 Bohn, Uriel
A1 Cajal, Teresa Ramón Y
A1 Duran-Poveda, Manuel
A1 Astorga, Beatriz González
A1 López-Alfonso, Ana
A1 Martínez, Javier Medina
A1 Porras, Ignacio
A1 Reina, Juan Jose
A1 Palacios, Nuria
A1 Grande, Enrique
A1 Cillán, Elena
A1 Matos, Ignacio
A1 Grau, Juan Jose
AB Axitinib, an antiangiogenic multikinase inhibitor (MKI), was evaluated in the compassionate use programme (CUP) in Spain (October 2012-November 2014). 47 patients with advanced radioactive iodine (RAI)-refractory differentiated thyroid cancer (DTC, n = 34) or medullary thyroid cancer (MTC, n = 13) with documented disease progression were treated with axitinib 5 mg b.i.d. The primary efficacy endpoint was objective response rate (ORR) by Response Evaluation Criteria In Solid Tumors (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. 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%) and 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 b.i.d. All-grade AEs included asthenia (53.2%), diarrhoea (36.2%), hypertension (31.9%) and mucositis (29.8%); grade 3/4 AEs included anorexia (6.4%), diarrhoea (4.3%) and cardiac toxicity (4.3%). 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.
YR 2017
FD 2017-07-07
LK http://hdl.handle.net/10668/11384
UL http://hdl.handle.net/10668/11384
LA en
DS RISalud
RD Apr 19, 2025