Alain Ravaud1, Christelle de la Fouchardière2, Philippe Caron3, Adelaïde Doussau4, Christine Do Cao5, Julien Asselineau4, Patrice Rodien6, Damien Pouessel7, Patricia Nicolli-Sire8, Marc Klein9, Claire Bournaud-Salinas10, Jean-Louis Wemeau5, Anne Gimbert11, Marie-Quitterie Picat4, Delphine Pedenon12, Laurence Digue12, Amaury Daste13, Bogdan Catargi14, Jean-Pierre Delord15. 1. Department of Medical Oncology, Bordeaux University Hospital, Bordeaux, France; Clinical Investigational Center, CIC. INSERM CIC 1401, Bordeaux University Hospital, Bordeaux, France; Bordeaux University, Bordeaux, France. Electronic address: alain.ravaud@chu-bordeaux.fr. 2. Department of Medical Oncology, Centre Leon Bérard, Lyon, France. 3. Department of Endocrinology, Toulouse University Hospital, Toulouse, France. 4. Methodology Research Unit, Bordeaux University Hospital, Bordeaux, France. 5. Department of Endocrinology, Lille University Hospital, Lille, France. 6. Department of Endocrinology, Angers University Hospital, Angers, France. 7. Department of Medical Oncology, Cancer Institute of Montpellier, Montpellier, France. 8. Department of Endocrinology, Marseille University Hospital, Marseille, France. 9. Department of Endocrinology, Nancy University Hospital, Nancy, France. 10. Department of Endocrinology, Lyon University Hospital, Lyon, France. 11. Pharmacovigilance Unit, Bordeaux University Hospital, Bordeaux, France. 12. Department of Medical Oncology, Bordeaux University Hospital, Bordeaux, France. 13. Department of Medical Oncology, Bordeaux University Hospital, Bordeaux, France; Bordeaux University, Bordeaux, France. 14. Department of Endocrinology, Bordeaux University Hospital, Bordeaux, France. 15. Department of Medical Oncology, Institut Claudius Régaud, IUCT, Toulouse, France.
Abstract
PURPOSE: Patients with advanced radioactive iodine resistant differentiated (MDTC) or medullary (MMTC) thyroid cancer had an unmet need. Early data showed promising efficacy of vascular endothelial growth factor receptor inhibitors. We investigated sunitinib in this setting. PATIENTS AND METHODS: This phase 2 trial enrolled MDTC, anaplastic (MATC) and MMTC patients in 1st line anti-angiogenic therapy with sunitinib at 50 mg/d, 4/6w. Objective response rate was the primary end-point. Secondary end-points were progression-free survival, overall survival and safety. RESULTS: Seventy-one patients were enrolled from August 2007 to October 2009, 41 MDTC/4 MATC patients and 26 MMTC patients. Patients received a median of 8 and 9 cycles, respectively. In the MDTC/MATC group, 13% of patients and 43% of cycles and in the MMTC group, 23% of the patients and 48.8% of cycles remained at 50 mg/d, respectively. The primary end-point was reached with an objective response rate of 22% (95% CI: 10.6-37.6) in MDTC patients and in 38.5% (95% CI: 22.6-56.4) in MMTC patients. No objective response was seen in MATC patients. Median progression-free survival and overall survival were 13.1 and 26.4 months in MDTC patients, 16.5 and 29.4 months in MMTC patients. The most frequent side effects were asthenia/fatigue (27.8% ≥ grade 3), mucosal (9.9% ≥ grade 3), cutaneous toxicities, hand-foot syndrome (18.3% ≥ grade 3). Of all, 14.1% had a cardiac event. Nine unexpected side effects were reported, out of which, five induced deaths. CONCLUSION: Sunitinib is active in MDTC and MMTC patients. Side effects were more severe than with previous reports. If using sunitinib, alternative schedule/dosage should be considered.
PURPOSE:Patients with advanced radioactive iodine resistant differentiated (MDTC) or medullary (MMTC) thyroid cancer had an unmet need. Early data showed promising efficacy of vascular endothelial growth factor receptor inhibitors. We investigated sunitinib in this setting. PATIENTS AND METHODS: This phase 2 trial enrolled MDTC, anaplastic (MATC) and MMTCpatients in 1st line anti-angiogenic therapy with sunitinib at 50 mg/d, 4/6w. Objective response rate was the primary end-point. Secondary end-points were progression-free survival, overall survival and safety. RESULTS: Seventy-one patients were enrolled from August 2007 to October 2009, 41 MDTC/4 MATCpatients and 26 MMTCpatients. Patients received a median of 8 and 9 cycles, respectively. In the MDTC/MATC group, 13% of patients and 43% of cycles and in the MMTC group, 23% of the patients and 48.8% of cycles remained at 50 mg/d, respectively. The primary end-point was reached with an objective response rate of 22% (95% CI: 10.6-37.6) in MDTCpatients and in 38.5% (95% CI: 22.6-56.4) in MMTCpatients. No objective response was seen in MATCpatients. Median progression-free survival and overall survival were 13.1 and 26.4 months in MDTCpatients, 16.5 and 29.4 months in MMTCpatients. The most frequent side effects were asthenia/fatigue (27.8% ≥ grade 3), mucosal (9.9% ≥ grade 3), cutaneous toxicities, hand-foot syndrome (18.3% ≥ grade 3). Of all, 14.1% had a cardiac event. Nine unexpected side effects were reported, out of which, five induced deaths. CONCLUSION:Sunitinib is active in MDTC and MMTCpatients. Side effects were more severe than with previous reports. If using sunitinib, alternative schedule/dosage should be considered.
Authors: Keith C Bible; Michael E Menefee; Chia-Chi Josh Lin; Michael J Millward; William J Maples; Boon Cher Goh; Nina J Karlin; Madeleine A Kane; Douglas R Adkins; Julian R Molina; Ross C Donehower; Wan-Teck Lim; Patrick J Flynn; Ronald L Richardson; Anne M Traynor; Joseph Rubin; Patricia M LoRusso; Robert C Smallridge; Jill K Burton; Vera J Suman; Aditi Kumar; Jessie S Voss; Kandalaria M Rumilla; Benjamin R Kipp; Ashish V Chintakuntlawar; Pamela Harris; Charles Erlichman Journal: Thyroid Date: 2020-07-29 Impact factor: 6.568