Activity of sunitinib in extraskeletal myxoid chondrosarcoma☆,
Introduction
Extraskeletal myxoid chondrosarcoma (EMC) is an exceedingly rare sarcoma, usually arising from soft tissues of extremities [1]. EMC is marked by reciprocal translocations involving the NR4A3 gene locus on chromosome 9. In most cases, NR4A3 fuses with the EWSR1 gene located on chromosome 22, but other partner genes, namely TAF15, TCF12 and TFG, were identified [1], [2]. EMC can be subdivided into the ‘conventional well-differentiated’ and the ‘cellular high-grade’ variants [1]. ‘Dedifferentiated’ EMC was also described [3]. The natural history of the disease is usually indolent, but a more aggressive course is observed in dedifferentiated cases. Ten-year survival ranges between 85% and 65%, with a 40% risk of metastases [4], [5]. Resistance to cytotoxic chemotherapy is common [4], [5], [6], [7], which urges the need to identify alternative therapeutic strategies.
We preliminarily reported on the activity of sunitinib in two EMC patients [8]. We herein corroborate our initial observation by analysing a series of 10 patients with metastatic EMC treated with sunitinib within a named-use program. The clinical behaviour was then analysed in the light of tumour karyotype, and of transcriptome, immunohistochemical and biochemical analyses.
Section snippets
Patients
This retrospective series includes 10 consecutive metastatic EMC patients, treated with sunitinib since July 2011 at the Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy. Performance status (Eastern Cooperative Oncology Group (ECOG)) ⩽ 3, adequate bone marrow and organ function were requested. All patients provided a written informed consent to a non-conventional medical treatment, selected in the lack of any effective therapy in the disease. Approval by the Institutional Review Board was
Patients
Ten consecutive patients received sunitinib from July 2011 to December 2013. All were evaluable for response. Eight patients are still on therapy, two stopped their treatment for progression.
Table 1 summarises patient characteristics and clinical findings.
All patients displayed disease progression according to RECIST within the 6 months before starting sunitinib.
Discussion
From July 2011, 10 patients with advanced, progressive EMC have been treated with continuous-dosing sunitinib. According to RECIST, we observed six PR, two SD and two progressive disease (PD). One of the two patients with SD had a minor (<30%) dimensional response. Responses were long-lasting (median PFS not yet reached), with two patients still on treatment at 2 years. No secondary resistances were observed. Intriguingly, all responsive cases presented the most common EWSR1–NR4A3 fusion. By
Conflict of interest statement
Stacchiotti S. – Pfizer: travel coverage for medical meetings, research funding. Glaxo Smith Kline: research funding.
Gronchi A. – Pfizer: honoraria, research funding.
Dei Tos A.P. – Pfizer: honoraria. Glaxo Smith Kline: honoraria, travel coverage for medical meeting.
Casali P.G. – Pfizer: advisory, honoraria, research funding. Glaxo Smith Kline: advisory, honoraria, research funding.
All remaining authors have declared no conflict of interest.
References (16)
- et al.
Myxoid chondrosarcoma with a translocation involving chromosomes 9 and 22
Cancer Genet Cytogenet
(1985) - et al.
Cloning and mapping of a human RBP56 gene encoding a putative RNA binding protein similar to FUS/TLS and EWS proteins
Genomics
(1996) - et al.
Skeletal and extraskeletal myxoid chondrosarcoma: a comparative clinicopathologic, ultrastructural, and molecular study
Cancer
(1998) - et al.
Extraskeletal myxoid chondrosarcoma: a review of 23 patients treated at a single referral center with long-term follow-up
Arch Orthop Trauma Surg
(2012) - et al.
Extraskeletal myxoid chondrosarcoma: a retrospective review from 2 referral centers emphasizing long-term outcomes with surgery and chemotherapy
Cancer
(2008) - et al.
Extraskeletal myxoid chondrosarcoma. Long-term experience with chemotherapy
Am J Clin Oncol
(1995) - Stacchiotti S, Dagrada G, Sanfilippo R, et al. Anthracycline-based chemotherapy in extraskeletal myxoid chondrosarcoma:...
Cited by (67)
Extraskeletal myxoid chondrosarcoma metastasis to a Meckel's diverticulum adenocarcinoma
2024, Revista Espanola de PatologiaDeepPurpose-based drug discovery in chondrosarcoma
2022, Chinese Journal of Plastic and Reconstructive SurgeryExtraskeletal myxoid chondrosarcoma: Clinical features and overall survival
2022, Cancer Treatment and Research CommunicationsUncommon and peculiar soft tissue sarcomas: Multidisciplinary review and practical recommendations. Spanish Group for Sarcoma research (GEIS –GROUP). Part II
2021, Cancer Treatment ReviewsCitation Excerpt :A small series of 10 patients treated with sunitinib (37.5 mg on a continuous daily dosing schedule) showed ORR of 60% and stable disease of 20%. All responders had EWSR1-NR4A3 fusion, whereas non-responders had TAF15-NR4A3 fusion [175]. The updated results showed a mPFS of 34 months, while OS had not been reached [176].
Role of immunotherapy in chondrosarcoma: A case report and review of the literature
2023, Therapeutic Advances in Medical Oncology
- ☆
Presented at 18th Connective Tissue Oncology Society (CTOS) Annual Meeting, 2013, New York, abs 1771775.
Funding: Grant from Associazione Italiana per la Ricerca sul Cancro (AIRC): IG 10300.
- 1
These authors equally contributed to the paper.