PMID- 28687563 OWN - NLM STAT- MEDLINE DCOM- 20171003 LR - 20190218 IS - 1479-683X (Electronic) IS - 0804-4643 (Linking) VI - 177 IP - 4 DP - 2017 Oct TI - Axitinib treatment in advanced RAI-resistant differentiated thyroid cancer (DTC) and refractory medullary thyroid cancer (MTC). PG - 309-317 LID - EJE-17-0243 [pii] LID - 10.1530/EJE-17-0243 [doi] AB - BACKGROUND: Axitinib, an antiangiogenic multikinase inhibitor (MKI), was evaluated in the compassionate use programme (CUP) in Spain (October 2012-November 2014). SUBJECTS AND METHODS: 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. 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%) 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%). 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. CI - (c) 2017 European Society of Endocrinology. FAU - Capdevila, Jaume AU - Capdevila J AD - Medical Oncology Department, Gastrointestinal and Endocrine Tumor Unit, Vall d'Hebron University Hospital, Universitat Autonoma de Barcelona, Barcelona, Spain. FAU - Trigo, Jose Manuel AU - Trigo JM AD - Medical Oncology Department, University Hospital Virgen de la Victoria, Malaga, Spain. FAU - Aller, Javier AU - Aller J AD - Endocrinology Department, University Hospital Puerta de Hierro, Madrid, Spain. FAU - Manzano, Jose Luis AU - Manzano JL AD - Medical Oncology Department, Catalan Oncology Institute (ICO-Badalona), University Hospital Germans Trias y Pujol, Barcelona, Spain. FAU - Adrian, Silvia Garcia AU - Adrian SG AD - Medical Oncology Department, University Hospital of Mostoles, Mostoles, Madrid, Spain. FAU - Llopis, Carles Zafon AU - Llopis CZ AD - Endocrinology and Nutrition Department, Vall d'Hebron University Hospital, Barcelona, Spain. FAU - Reig, Oscar AU - Reig O AD - Medical Oncology Department, Translational Genomics and Targeted Therapeutics in Solid Tumors (IDIBAPS), Hospital Clinic of Barcelona, Barcelona, Spain. FAU - Bohn, Uriel AU - Bohn U AD - Medical Oncology Department, University Hospital of Gran Canaria Doctor Negrin, Las Palmas, Spain. FAU - Cajal, Teresa Ramon Y AU - Cajal TRY AD - Medical Oncology Department, University Hospital of Santa Creu i Sant Pau, Barcelona, Spain. FAU - Duran-Poveda, Manuel AU - Duran-Poveda M AD - General and Endocrine Surgery Department, University Hospital Rey Juan Carlos, Madrid, Spain. FAU - Astorga, Beatriz Gonzalez AU - Astorga BG AD - Medical Oncology Department, University Hospital Virgen de las Nieves, Granada, Spain. FAU - Lopez-Alfonso, Ana AU - Lopez-Alfonso A AD - Medical Oncology Department, University Hospital Infanta Leonor, Madrid, Spain. FAU - Martinez, Javier Medina AU - Martinez JM AD - Medical Oncology Department, Hospital Virgen de la Salud, Toledo, Spain. FAU - Porras, Ignacio AU - Porras I AD - Medical Oncology Department, University Hospital Reina Sofia, Cordoba, Spain. FAU - Reina, Juan Jose AU - Reina JJ AD - Medical Oncology Department, University Hospital Virgen Macarena, Sevilla, Spain. FAU - Palacios, Nuria AU - Palacios N AD - Endocrinology Department, University Hospital Puerta de Hierro, Madrid, Spain. FAU - Grande, Enrique AU - Grande E AD - Medical Oncology Department, University Hospital Ramon y Cajal, Madrid, Spain. FAU - Cillan, Elena AU - Cillan E AD - Medical Oncology Department, University Hospital of Santa Creu i Sant Pau, Barcelona, Spain. FAU - Matos, Ignacio AU - Matos I AD - Medical Oncology Department, Gastrointestinal and Endocrine Tumor Unit, Vall d'Hebron University Hospital, Universitat Autonoma de Barcelona, Barcelona, Spain. FAU - Grau, Juan Jose AU - Grau JJ AD - Medical Oncology Department, University of Barcelona, Hospital Clinic of Barcelona, Barcelona, Spain. LA - eng PT - Journal Article DEP - 20170707 PL - England TA - Eur J Endocrinol JT - European journal of endocrinology JID - 9423848 RN - 0 (Imidazoles) RN - 0 (Indazoles) RN - 0 (Iodine Radioisotopes) RN - 0 (Protein Kinase Inhibitors) RN - C9LVQ0YUXG (Axitinib) RN - Thyroid cancer, medullary SB - IM MH - Adult MH - Aged MH - Aged, 80 and over MH - Axitinib MH - Carcinoma, Neuroendocrine/diagnostic imaging/drug therapy/epidemiology MH - Female MH - Humans MH - Imidazoles/*therapeutic use MH - Indazoles/*therapeutic use MH - *Iodine Radioisotopes MH - Longitudinal Studies MH - Magnetic Resonance Imaging/methods MH - Male MH - Middle Aged MH - Positron Emission Tomography Computed Tomography/methods MH - Protein Kinase Inhibitors/*therapeutic use MH - Retrospective Studies MH - Spain/epidemiology MH - Thyroid Neoplasms/*diagnostic imaging/*drug therapy/epidemiology MH - Treatment Outcome EDAT- 2017/07/09 06:00 MHDA- 2017/10/04 06:00 CRDT- 2017/07/09 06:00 PHST- 2017/03/23 00:00 [received] PHST- 2017/05/25 00:00 [revised] PHST- 2017/06/29 00:00 [accepted] PHST- 2017/07/09 06:00 [pubmed] PHST- 2017/10/04 06:00 [medline] PHST- 2017/07/09 06:00 [entrez] AID - EJE-17-0243 [pii] AID - 10.1530/EJE-17-0243 [doi] PST - ppublish SO - Eur J Endocrinol. 2017 Oct;177(4):309-317. doi: 10.1530/EJE-17-0243. Epub 2017 Jul 7.