Molecular Targeted Therapy in the Treatment of Chordoma: A Systematic Review

Abstract

Objectives: Chordoma is a rare bone malignancy that affects the spine and skull base. Treatment dilemma leads to a high rate of local relapse and distant metastases. Molecular targeted therapy (MTT) is an option for advanced chordoma, but its therapeutic efficacy and safety have not been investigated systematically. Therefore, a systematic review was conducted on studies reporting MTT regimens for chordoma.Methods: Clinical trials, case series and case reports on chordoma MTT were identified using MEDLINE, Cochrane library and EMBASE, and systematically reviewed. Data on clinical outcomes, such as median overall survival, progression-free survival, response rate and adverse events (AEs) were extracted and analyzed.Results: Thirty-three eligible studies were selected for the systematic review, which indicated that imatinib and erlotinib were the most frequently used molecular targeted inhibitors (MTIs) for chordoma. For PDGFR-positive and/or EGFR-positive chordoma, clinical benefits were achieved with acceptable AEs. Monotherapy is preferred as the first-line of treatment, and combined drug therapy as the second-line treatment. In addition, the brachyury vaccine has shown promising results.Conclusions: The selection of MTIs for patients with advanced or relapsed chordoma should be based on gene mutation screening and immunohistochemistry (IHC). Monotherapy of TKIs is recommended as the first-line management, and combination therapy (two TKIs or TKI plus mTOR inhibitor) may be the choice for drug-resistant chordoma. Brachyury vaccine is a promising therapeutic strategy and requires more clinical trials to evaluate its safety and efficacy.

Chondroid chordoma of the parapharyngeal space: A case report and review of literature

“…Molecular targeted therapy (MTT), e.g. erlotinib and imatinib is an option for advanced chordoma, but it requires more clinical trials to evaluate its safety and efficacy [16].…”

Unexpected benefit from an ‘old’ metronomic chemotherapy regimen in advanced chordoma

“…There are no formally approved drugs in the advanced setting 1. The tyrosine kinase imatinib has been often used in progressive cases,2 while standard chemotherapy is considered poorly effective 1. Here, we report the case of a 79-year-old man, with cardiac and renal comorbidities, with a pathological diagnosis of sacral chordoma from March 2013, when the patient first underwent surgery.…”

“…Chordoma is a rare slow-growing tumour arising from notochord remnants most often in the skull base or sacrum in patients of all ages. There are no formally approved drugs in the advanced setting 1. The tyrosine kinase imatinib has been often used in progressive cases,2 while standard chemotherapy is considered poorly effective 1.…”

Invited Review: Dysregulation of chromatin remodellers in paediatric brain tumours – SMARCB1 and beyond

“…The immunohistochemical absence of INI‐1 thus prompts the question if these tumours are susceptible to the same therapeutic approaches as ATRT such as, for example, EZH2 inhibition, which have been studied widely in MRT. A clinical trial using the EZH2 inhibitor tazemetostat [91] has shown two partial responses in children with INI‐1‐deficient chordomas.…”