Imatinib in advanced chordoma: A retrospective case series analysis
Introduction
Chordoma is a rare primary bone tumour that arises from notochord remnants on axial bones (skull base and spine). Chordoma is usually a slow growing, locally aggressive disease, although up to 30% of patients can develop distant metastases. Surgery with wide margins is the mainstay of therapy in these patients, but more than 50% of them suffer from a local recurrence [1], [2]. High-dose radiotherapy (RT) can be an option in the case of locally advanced disease [3], [4], and as adjuvant therapy after a positive-margin surgery [5]. Cytotoxic chemotherapy is generally inactive in this tumour, and at present, no active drugs are approved for this indication. Imatinib had previously shown activity in chordoma. A multicentric Phase II trial with imatinib in patients with advanced disease showed only one partial response according to the Response Evaluation Criteria in Solid Tumors (RECIST) [6] but 70% of patients remained stable, with a median progression free survival (PFS) of 9 months [7].
Our institution previously reported on the outcome of 138 patients with primary, completely resected chordoma, observing that >50% of them died of disease [1]. Given this evidence and the previously reported data on the activity of imatinib, we decided to extend the use of imatinib within a compassionate-use programme that was opened after the closure of the Phase II trial, at Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy (INT) from August 2002 to November 2010.
Here we report on the retrospective series of advanced chordoma patients treated with imatinib within that programme.
Section snippets
Patients
This retrospective series includes 48 adult patients with progressive, locally advanced or metastatic chordoma consecutively treated with imatinib as single agent between August 2002 and November 2010 at INT. Performance Status (Eastern Cooperative Oncology Group) (ECOG) ⩽3 and adequate bone marrow and organ function were requested in all cases. Histologic diagnosis was confirmed by central review. Expression of PDGFB and/or PDGFRB was assessed in all patients by immunohistochemistry (IHC)
Results
Forty-eight patients were consecutively treated. Baseline patient characteristics are summarised in Table 1. PDGFRB and/or PDGFB was evaluable and positive in 45 patients. Tissue was not adequate for the analysis (due to decalcification) in three patients. For 45 patients imatinib was the first systemic therapy (one patient had previously received two cycles of high-dose ifosfamide, one received one cycle of carboplatin and gemcitabine, another received three cycles of fludarabine,
Discussion
The present retrospective study reports on 48 patients with progressive locally advanced or metastatic PDGFRB/PDGFB positive chordoma consecutively treated with imatinib as single agent within a compassionate-use programme, confirming the previously reported data on the activity of imatinib in advanced chordoma. According to RECIST, no PR were detected, with 74% of patients remaining stable, but a PET metabolic response was detected in 40% of the evaluated patients. At a median follow up of 24.5
Conclusions
In conclusion, this retrospective series confirms the previously reported data of activity of imatinib in advanced chordoma. Treatment of chordoma still represents a challenge, with an urgent need of therapeutic options for patients with advanced disease. A global effort is being made, with the very valuable help of the patient advocacy groups. In this sense, a position paper from the international scientific community has recently been published [17], a clinical trial with the combination of
Conflict of interest statement
Nadia Hindi, Elena Palassini, Silvia Stacchiotti: Research funds from Novartis to their Institution; Paolo G Casali: Honoraria, compensated advisory board, research funds to his Institution and travel cost from Novartis; Alessandro Gronchi: Honoraria and compensated advisory board from Novartis; Carlo Morosi, Antonella Messina, Silvana Pilotti, Elena Tamborini, Stefano Radaelli: Conflicts of interest: none.
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Cited by (0)
Presented at Connective Tissue Oncology Society Annual Meeting 2014, Berlin, Abstract # 85.
The corresponding author has received a research grant from the Spanish Society of Medical Oncology (SEOM).