Limited efficacy of lenvatinib in heavily pretreated anaplastic thyroid cancer: a French overview

Anaplastic thyroid cancer (ATC) is a rare lethal disease. Lenvatinib is an off-label therapeutic option for ATC in most countries, except in Japan. The aim of this multicentre retrospective survey was to analyse the efficacy and the toxicity profile of off-label lenvatinib treatment in all adults advanced ATC patients, in France. Of the 23 patients analysed (14 males; mean age 64 years), 15 were pure ATC and 8 were mixed tumors (i.e. with a differentiated or poorly differentiated component). Prior treatments included neck external beam irradiation in 74%, at least one line of chemotherapy in 22 cases, 2 lines of chemotherapy in 11 patients, other TKI in 4 cases. A central RECIST assessment was performed. Since lenvatinib initiation, median PFS was 2.7 months (95%CI; 1.9-3.5) and median OS was 3.1 months (95%CI; 0.6-5.5). OS was significantly longer in case of mixed tumors compared with pure ATC (6.3 vs 2.7 months, p=0.026). Best tumor response was partial response in 2 cases and stable disease in 7. Clinical improvement was achieved in 7 patients. Lethal adverse events occurred in 3 patients, consisting in haemoptysis in 2 cases and pneumothorax in 1 case. Among long-surviving ATC patients (> 6 months), 4 underwent biopsy of distant metastasis, revealing poorly differentiated histology; 3 of them had initial mixed ATC histology. Efficacy of lenvatinib appears limited, although pure versus mixed ATC disclose differences in disease aggressiveness and treatment response. Long-surviving ATC patients might benefit from biopsy of persistent disease, searching for histological transition or molecular target.