Role of salvage targeted therapy in differentiated thyroid cancer patients who failed first-line sorafenib

J Clin Endocrinol Metab. 2014 Jun;99(6):2086-94. doi: 10.1210/jc.2013-3588. Epub 2014 Mar 14.

Abstract

Context: Sorafenib, a tyrosine kinase inhibitor, is a common first-line therapy for advanced differentiated thyroid cancer (DTC). However, responses are not durable and drug toxicity remains a problem.

Objective: The objective of the study was to determine the efficacy of salvage therapy after first-line sorafenib failure.

Design: This was a retrospective review at M. D. Anderson Cancer Center from January 2005 to May 2013.

Patients: The study included patients with metastatic DTC who received salvage therapy after their initial sorafenib failure (group 2). PATIENTS who received first-line sorafenib only (group 1) were evaluated for comparison of overall survival (OS).

Outcome measures: Progression-free survival, best response, and median OS were measured.

Results: Sixty-four patients with metastatic, radioactive iodine refractory DTC were included; 35 were in group 1 and 25 were in group 2, and the groups were well balanced. Median OS of all 64 patients receiving first line sorafenib was 37 months; median OS was significantly longer with salvage therapy compared with sorafenib alone (58 vs 28 months, P = .013). In group 2, 17 patients were evaluable for best response, although two patients had toxicity with sorafenib, which was discontinued before restaging. Best responses with first-line sorafenib were partial response in 2 of 15 (13%), stable disease in 10 of 15 (67%), and progressive disease in 3 of 15 (20%) patients. With salvage therapy, partial responses were seen in 7 of 17 (41%) and stable disease in 10 of 17 (59%) patients. Median progression-free survival was 7.4 months with first-line sorafenib and 11.4 months with salvage therapy. Salvage therapy included sunitinib (n = 4), pazopanib (n = 3), cabozantinib (n = 4), lenvatinib (n = 3), and vemurafenib (n = 3).

Conclusions: Other targeted agents are effective salvage treatments after sorafenib failure, despite similar mechanisms of action, and should be offered to patients who are able to receive salvage therapy.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Carcinoma, Papillary, Follicular / drug therapy*
  • Carcinoma, Papillary, Follicular / mortality
  • Carcinoma, Papillary, Follicular / pathology
  • Chemotherapy, Adjuvant
  • Drug Resistance, Neoplasm / drug effects
  • Female
  • Humans
  • Male
  • Middle Aged
  • Molecular Targeted Therapy*
  • Neoadjuvant Therapy
  • Neoplasm Metastasis
  • Niacinamide / analogs & derivatives*
  • Niacinamide / therapeutic use
  • Phenylurea Compounds / therapeutic use*
  • Protein Kinase Inhibitors / therapeutic use*
  • Retrospective Studies
  • Salvage Therapy / methods*
  • Sorafenib
  • Thyroid Neoplasms / drug therapy*
  • Thyroid Neoplasms / mortality
  • Thyroid Neoplasms / pathology
  • Treatment Failure

Substances

  • Phenylurea Compounds
  • Protein Kinase Inhibitors
  • Niacinamide
  • Sorafenib