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 multicenter retrospective survey was to analyze 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, two 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 two cases and stable disease in seven. Clinical improvement was achieved in seven patients. Lethal adverse events occurred in three patients, consisting in haemoptysis in two cases and pneumothorax in one case. Among long-surviving ATC patients (>6 months), four underwent biopsy of distant metastasis, revealing poorly differentiated histology; three of them had initial mixed ATC histology. Efficacy of lenvatinib appears limited, although pure vs 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.