Cetuximab and EGFR inhibitors in patients with neurological symptoms due to chordoma.

Abstract

10024 Background: Chordomas are rare tumours located along the neuraxis, showing limited sensitivity to radiotherapy and lack of response to chemotherapy. However, tyrosine kinase inhibitors (TKIs) have been reported to have an effect. Following the failure of single-agent treatment in a young patient using cetuximab, we decided to treat patients (pts) with neurological symptoms with dual targeting of the epidermal growth factor receptor (EGFR), based on a case report by Hof et al., who successfully used dual targeting of EGFR, and supporting in vitro data. Methods: Eight consecutive pts with neurological symptoms at referral were treated with cetuximab (250 mg/m2 weekly) and an EGFR signalling inhibitor (250 mg gefitinib or 150 mg erlotinib daily). The duration of treatment was not decided in advance. Results: EGFR expression on tumour cells was variable but present in all pts. Six pts were evaluable. One tetraplaegic pt died of an unknown cause and one pt on lithium carbonate discontinued treatment before the first follow-up due to renal toxicity. Four pts showed neurological improvement. Two of these regained and one improved the ability to walk, and a fourth, with a sacral tumour, improved his voiding ability. The fifth pt had clinically stable disease and, although the PET scan showed improvement, the treatment had to be discontinued due to skin toxicity. One pt showed progressive disease. In the four pts responding neurologically, improvement was noted already by the end of the third week. Three pts were retreated without failure while on treatment. The first pt who regained the ability to walk is still walking at 52+ months. This pt, while still responsive to cetuximab and erlotinib, has failed to respond to single-agent treatment with imatinib, sorafenib or everolimus. The second pt who regained walking ability had severe alcoholism and died while being treated. The third is still walking at 16+ months. All pts exhibited significant cutaneous side effects, in some cases necessitating intermittent interruption of therapy. Conclusions: Treatment with cetuximab and TKIs can thus achieve meaningful and long-lasting clinical improvement in pts with paresis due to chordoma, and is feasible in pts with limited comorbidities.