Sunitinib in patients with advanced thymic malignancies: Cohort from the French RYTHMIC network

Lung Cancer. 2016 Jul:97:99-104. doi: 10.1016/j.lungcan.2016.04.024. Epub 2016 May 3.

Abstract

Background: Sunitinib is a potent oral tyrosine kinase inhibitor of VEGFRs, KIT, and PDGFRs. In a single arm phase II trial, sunitinib has demonstrated its potential activity in refractory thymic carcinoma (TC) and thymoma (T). Taking advantage of the French RYTHMIC network prospective database, we investigated the off-label efficacy of sunitinib in previously-treated thymic epithelial tumors (TETs) patients not included in a clinical trial.

Methods: RYTHMIC database started in 2012, and prospectively collects clinical, imaging, treatment, and follow-up data of all patients diagnosed with TET, for whom management is discussed at a national multidisciplinary tumor board. All patients who received sunitinib were selected for this analysis.

Results: 28 patients from 7 institutions were identified, including 20 TC and 8T; 32% of patients were females, and median age was 50 years. Fifteen patients (54%) received sunitinib as ≥4th line treatment. The initial daily dose of sunitinib was 50mg in 11 patients, 37.5mg in 16 patients and 25mg in 1 patient. Sunitinib adverse events were all manageable and tolerable; 8 patients had to stop sunitinib due to toxicity after a median duration of treatment of 2.7 months. In the overall population, disease control rate was of 63% (86% for T, and 55% for TC); overall response rate was 22% (29% for T, and 20% for TC). Median PFS in the whole population was 3.7 months (5.4 months for T, and 3.3 months for TC, p=0.097). The median overall survival in the whole population was 15.4 months: survival was not reached for T, and was 12.3 months for TC patients (p=0.043).

Conclusion: Sunitinib is an active treatment in TETs irrespective of histological subtype, supporting the use of tyrosine kinase inhibitors with anti-angiogenic activity as alternative treatment options in refractory disease.

Keywords: Second line; Sunitinib; Thymic carcinoma; Thymoma.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Angiogenesis Inhibitors / administration & dosage*
  • Angiogenesis Inhibitors / pharmacology
  • Clinical Trials, Phase II as Topic
  • Disease-Free Survival
  • Female
  • Humans
  • Indoles / administration & dosage*
  • Indoles / pharmacology
  • Male
  • Middle Aged
  • Multicenter Studies as Topic
  • Neoplasm Staging
  • Neoplasms, Glandular and Epithelial / drug therapy
  • Prospective Studies
  • Protein Kinase Inhibitors / administration & dosage*
  • Protein Kinase Inhibitors / pharmacology
  • Proto-Oncogene Proteins c-kit
  • Pyrroles / administration & dosage*
  • Pyrroles / pharmacology
  • Retrospective Studies
  • Sunitinib
  • Thymoma / classification
  • Thymoma / drug therapy*
  • Thymoma / mortality
  • Thymoma / pathology
  • Thymus Neoplasms / classification
  • Thymus Neoplasms / drug therapy*
  • Thymus Neoplasms / mortality
  • Thymus Neoplasms / pathology
  • Treatment Outcome
  • Young Adult

Substances

  • Angiogenesis Inhibitors
  • Indoles
  • Protein Kinase Inhibitors
  • Pyrroles
  • Proto-Oncogene Proteins c-kit
  • Sunitinib

Supplementary concepts

  • Thymic epithelial tumor