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

Abstract

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.

Anaplastic Thyroid Carcinoma: An Update

“…To our knowledge, no trials have looked at mTOR inhibitors in the context of ATC with mutation in the PI3K/AKT/mTOR pathway. Antiangiogenic treatments such as lenvatinib [ 132 ], a multikinase inhibitor approved in differentiated thyroid cancers, have shown initially encouraging results but limited activity in subsequent studies, with a risk of bleeding and fistula as this disease often invades the trachea, esophagus and vessels, and are thus not recommended [ 2 , 77 , 133 ]. A recent prospective phase II trial was halted for futility as the minimum ORR threshold of 15% was not met upon interim analysis with a 2.9% response rate, a median PFS of 2.6 months and a median OS of 3.2 months [ 134 ].…”

Efficacy and Safety of Lenvatinib in Anaplastic Thyroid Carcinoma: A Meta-Analysis

“…We initially identified 349 studies. Finally, our study included 10 studies, namely, 2 prospective studies (13,18) and 8 retrospective studies (19)(20)(21)(22)(23)(24)(25)(26) (Figure 1). The characteristics of the study are shown in Table 1.…”

“…Two single-arm studies (13, 18) scored 12 points using the MINORS index, which were acceptable for the current metaanalysis. Eight retrospective studies (19)(20)(21)(22)(23)(24)(25)(26) were evaluated using the JBI Critical Appraisal Checklist for Case Series (Table 2).…”

“…The OS K-M curves were reported in six studies (18)(19)(20)(21)(22)24), and the pooled median overall survival (mOS) was 3.16 (95% CI, 2.17-5.64) months (Figure 3B), with the 3-month OS rate (OSR-3m), OSR-6m, OSR-9m, OSR-12m, and OSR-15m being 64.0%, 39.3%, 29.7%, 18.9%, and 14.2% (Figure 4B), respectively.…”

Combination of Lenvatinib and Pembrolizumab as Salvage Treatment for Paucicellular Variant of Anaplastic Thyroid Cancer: A Case Report

“…During the last decade, it has been emerging that ATC is a heterogeneous disease and that a more personalized approach could improve the patient prognosis. In this context, a recent French study showed that, among ATC patients treated with lenvatinib, the long-term survivors had a mixed histology of ATC combined with a more differentiated component [ 7 ]. Paucicellular ATC is an infrequent variant of ATC, which was associated with a better (although still poor) prognosis than classical ATC [ 8 ].…”