Jaume Capdevila1, José Manuel Trigo2, Javier Aller3, José Luís Manzano4, Silvia García Adrián5, Carles Zafón Llopis6, Òscar Reig7, Uriel Bohn8, Teresa Ramón Y Cajal9, Manuel Duran-Poveda10, Beatriz González Astorga11, Ana López-Alfonso12, Javier Medina Martínez13, Ignacio Porras14, Juan Jose Reina15, Nuria Palacios3, Enrique Grande16, Elena Cillán9, Ignacio Matos1, Juan Jose Grau17. 1. Medical Oncology Department, Gastrointestinal and Endocrine Tumor Unit, Vall d'Hebron University Hospital, Universitat Autònoma de Barcelona, Barcelona, Spain. 2. Medical Oncology Department, University Hospital Virgen de la Victoria, Málaga, Spain. 3. Endocrinology Department, University Hospital Puerta de Hierro, Madrid, Spain. 4. Medical Oncology Department, Catalan Oncology Institute (ICO-Badalona), University Hospital Germans Trias y Pujol, Barcelona, Spain. 5. Medical Oncology Department, University Hospital of Móstoles, Móstoles, Madrid, Spain. 6. Endocrinology and Nutrition Department, Vall d'Hebron University Hospital, Barcelona, Spain. 7. Medical Oncology Department, Translational Genomics and Targeted Therapeutics in Solid Tumors (IDIBAPS), Hospital Clínic of Barcelona, Barcelona, Spain. 8. Medical Oncology Department, University Hospital of Gran Canaria Doctor Negrín, Las Palmas, Spain. 9. Medical Oncology Department, University Hospital of Santa Creu i Sant Pau, Barcelona, Spain. 10. General and Endocrine Surgery Department, University Hospital Rey Juan Carlos, Madrid, Spain. 11. Medical Oncology Department, University Hospital Virgen de las Nieves, Granada, Spain. 12. Medical Oncology Department, University Hospital Infanta Leonor, Madrid, Spain. 13. Medical Oncology Department, Hospital Virgen de la Salud, Toledo, Spain. 14. Medical Oncology Department, University Hospital Reina Sofía, Córdoba, Spain. 15. Medical Oncology Department, University Hospital Virgen Macarena, Sevilla, Spain. 16. Medical Oncology Department, University Hospital Ramón y Cajal, Madrid, Spain. 17. Medical Oncology Department, University of Barcelona, Hospital Clínic of Barcelona, Barcelona, Spain.
Abstract
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.
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.
Authors: J Capdevila; J C Galofré; E Grande; C Zafón Llopis; T Ramón Y Cajal Asensio; E Navarro González; P Jiménez-Fonseca; J Santamaría Sandi; J M Gómez Sáez; G Riesco Eizaguirre Journal: Clin Transl Oncol Date: 2016-10-04 Impact factor: 3.405
Authors: Matti L Gild; Venessa H M Tsang; Roderick J Clifton-Bligh; Bruce G Robinson Journal: Nat Rev Endocrinol Date: 2021-02-18 Impact factor: 43.330
Authors: Ethan J Harris; Glenn J Hanna; Nicole Chau; Guilherme Rabinowits; Robert Haddad; Danielle N Margalit; Jonathan Schoenfeld; Roy B Tishler; Justine A Barletta; Matthew Nehs; Pasi Janne; Julian Huang; Phillip Groden; Alec Kacew; Jochen Lorch Journal: Front Oncol Date: 2019-02-26 Impact factor: 6.244