Response to Sunitinib ‘Exceptional’ In Advanced, Refractory Thymic Carcinoma

Promising phase II findings for sunitinib in advanced thymic carcinoma patients who have failed post-surgical palliative platinum-based chemotherapy

medwireNews: Patients with chemotherapy-refractory thymic carcinoma, but not thymoma, respond to treatment with the Tyrosine kinase inhibitor sunitinib, research suggests.

“[T]hese findings are the first prospective data of a targeted drug to show clinical activity in heavily pretreated patients with thymic carcinoma”, write Giuseppe Giaccone, from Georgetown University in Washington D.C, USA, and team.

In this phase II trial, thymic carcinoma and thymoma patients whose disease had progressed after at least one previous platinum-based chemotherapy treatment received open-label oral sunitinib at a dose of 50 mg daily in 6-week cycles, where each cycle included a 2-week break from treatment.

Of the 23 patients with thymic carcinoma, six achieved a partial response, 15 had stable disease and two had progressive disease, giving a rate of disease control of 91%.

Only one thymoma patient had a partial response, 12 had stable disease and three progressed. Although disease control was achieved in 81% of patients, the response to sunitinib was judged “insufficient” as per prespecified criteria requiring that two or more of the 16 patients enrolled would achieve a response.

Lymphocytopenia, fatigue and oral mucositis were the most frequent grade 3 or higher toxicities, with each observed in 20% of the 40 patients who received at least one dose of sunitinib.

Five (13%) patients had decreases in left-ventricular ejection fraction, of which three were grade 3 events, a frequency comparable with previous studies and considered “acceptable” by the researchers. But given the concurrent cardiac risk factors in patients with thymic epithelial tumours, they recommend careful monitoring of cardiac function while receiving sunitinib.

“[O]ur findings indicate that sunitinib could be a treatment option for patients with thymic carcinoma whose disease has progressed after platinum-based chemotherapy, a population for whom, currently, no standard treatments are available”, the team concludes in The Lancet Oncology.

Alexander Marx and Cleo-Aron Weis, from University Medical Centre Mannheim in Germany, note in an accompanying comment that this trial represents “major progress” in thymic carcinoma treatment, but add that several aspects, such as the molecular and cellular targets of sunitinib in this condition, remain to be elucidated.

They conclude: “To identify cellular biomarkers predicting the response of thymic carcinoma to sunitinib, future clinical trials should be complemented by studies of polymorphisms of immunoregulatory genes and by histological and molecular pathological investigations comparing features of neoplastic and non-neoplastic stromal components of pretherapeutic and, ideally, sequential thymic carcinoma biopsy samples from patients with a good and poor response to sunitinib.”

References

Thomas A, Rajan A, Berman A, et al. Sunitinib in patients with chemotherapy-refractory thymoma and thymic carcinoma: an open-label phase 2 trial. Lancet Oncol; Advance online publication 12 January 2015. doi:10.1016/S1470-2045(14)71181-7

Marx A, Weis C-A. Sunitinib in thymic carcinoma: enigmas still unresolved. Lancet Oncol; Advance online publication 12 January 2015. doi:10.1016/ S1470-2045(15)70010-0

medwireNews (www.medwireNews.com) is an independent clinical news service provided by Springer Healthcare Limited. © Springer Healthcare Ltd; 2015