Cixutumumab for patients with recurrent or refractory advanced thymic epithelial tumours: a multicentre, open-label, phase 2 trial

Lancet Oncol. 2014 Feb;15(2):191-200. doi: 10.1016/S1470-2045(13)70596-5. Epub 2014 Jan 15.


Background: No standard treatment exists for refractory or relapsed advanced thymic epithelial tumours. We investigated the efficacy of cixutumumab, a fully human IgG1 monoclonal antibody targeting the insulin-like growth factor 1 receptor in thymic epithelial tumours after failure of previous chemotherapy.

Methods: Between Aug 25, 2009, and March 27, 2012, we did a multicentre, open-label, phase 2 trial in patients aged 18 years or older with histologically confirmed recurrent or refractory thymic epithelial tumours. We enrolled individuals who had progressed after at least one previous regimen of platinum-containing chemotherapy, had an Eastern Cooperative Oncology Group performance status of 0 or 1, and had measurable disease and adequate organ function. Eligible patients received intravenous cixutumumab (20 mg/kg) every 3 weeks until disease progression or development of intolerable toxic effects. The primary endpoint was the frequency of response, analysed on an intention-to-treat basis. We also did pharmacodynamic studies. This trial is registered with, number NCT00965250.

Findings: 49 patients were enrolled (37 with thymomas and 12 with thymic carcinomas) who received a median of eight cycles of cixutumumab (range 1-46). At the final actuarial analysis when follow-up data were updated (Nov 30, 2012), median potential follow-up (from on-study date to most current follow-up date) was 24·0 months (IQR 17·3-36·9). In the thymoma cohort, five (14%) of 37 patients (95% CI 5-29) achieved a partial response, 28 had stable disease, and four had progressive disease. In the thymic carcinoma cohort, none of 12 patients (95% CI 0-26) had a partial response, five had stable disease, and seven had progressive disease. The most common grade 3-4 adverse events in both cohorts combined were hyperglycaemia (five [10%]), lipase elevation (three [6%]), and weight loss, tumour pain, and hyperuricaemia (two each [4%]). Nine (24%) of 37 patients with thymoma developed autoimmune conditions during treatment (five were new-onset disorders), the most common of which was pure red-cell aplasia. Two (4%) patients died; one was attributed to disease progression and the other to disease-related complications (respiratory failure, myositis, and an acute coronary event), which could have been precipitated by treatment with cixutumumab.

Interpretation: Cixutumumab monotherapy is well-tolerated and active in relapsed thymoma. Development of autoimmunity during treatment needs further investigation.

Funding: Division of Cancer Treatment and Diagnosis at the National Cancer Institute (National Institutes of Health), ImClone Systems.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antibodies, Monoclonal / adverse effects
  • Antibodies, Monoclonal / therapeutic use*
  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / therapeutic use*
  • Autoimmunity / drug effects
  • Disease Progression
  • Disease-Free Survival
  • Female
  • Humans
  • Intention to Treat Analysis
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local / drug therapy*
  • Neoplasm Recurrence, Local / immunology
  • Neoplasm Recurrence, Local / mortality
  • Neoplasm Recurrence, Local / pathology
  • Neoplasms, Glandular and Epithelial / drug therapy*
  • Neoplasms, Glandular and Epithelial / immunology
  • Neoplasms, Glandular and Epithelial / mortality
  • Neoplasms, Glandular and Epithelial / pathology
  • Receptor, IGF Type 1 / antagonists & inhibitors
  • Receptor, IGF Type 1 / immunology
  • Thymus Neoplasms / drug therapy*
  • Thymus Neoplasms / immunology
  • Thymus Neoplasms / mortality
  • Thymus Neoplasms / pathology
  • Time Factors
  • Treatment Outcome


  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents
  • cixutumumab
  • Receptor, IGF Type 1

Supplementary concepts

  • Thymic epithelial tumor

Associated data