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

in Endocrine-Related Cancer
Authors:
Clotilde Sparano Nuclear Medicine and Endocrine Oncology, Gustave Roussy, Université Paris Saclay, Villejuif, France
Endocrinology Unit, Department of Experimental and Clinical Biomedical Sciences ‘Mario Serio’, University of Florence, Florence, Italy

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Yann Godbert Nuclear Medicine, and Thyroid Oncology Department, Institut Bergonié, Bordeaux, France

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Marie Attard Radiology, Gustave Roussy and Université Paris Saclay, Villejuif, France

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Christine Do Cao Endocrinology, Diabetology and Metabolism, CHRU Lille, Lille, France

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Slimane Zerdoud Nuclear medicine, Claudius-Regaud Institute, Oncology University Institute-IUCT-Oncopole, Toulouse, France

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Nathalie Roudaut Department of Endocrinology, University Hospital of Brest, Brest, France

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Charlotte Joly Department of Oncology, Henri-Mondor Hospital, Créteil, France

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Amandine Berdelou Nuclear Medicine and Endocrine Oncology, Gustave Roussy, Université Paris Saclay, Villejuif, France

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Julien Hadoux Nuclear Medicine and Endocrine Oncology, Gustave Roussy, Université Paris Saclay, Villejuif, France

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Livia Lamartina Nuclear Medicine and Endocrine Oncology, Gustave Roussy, Université Paris Saclay, Villejuif, France

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Martin Schlumberger Nuclear Medicine and Endocrine Oncology, Gustave Roussy, Université Paris Saclay, Villejuif, France

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Sophie Leboulleux Nuclear Medicine and Endocrine Oncology, Gustave Roussy, Université Paris Saclay, Villejuif, France

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Correspondence should be addressed to S Leboulleux: Sophie.LEBOULLEUX@gustaveroussy.fr
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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.

 

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  • Begum S, Rosenbaum E, Henrique R, Cohen Y, Sidransky D & Westra WH 2004 BRAF mutations in anaplastic thyroid carcinoma: implications for tumor origin, diagnosis and treatment. Modern Pathology 17 13591363. (https://doi.org/10.1038/modpathol.3800198)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Berdelou A, Borget I, Godbert Y, Nguyen T, Garcia ME, Chougnet CN, Ferru A, Buffet C, Chabre O & Huillard O et al. 2018 Lenvatinib for the treatment of radioiodine-refractory thyroid cancer in real-life practice. Thyroid 28 7278. (https://doi.org/10.1089/thy.2017.0205)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Bonhomme B, Godbert Y, Perot G, Al Ghuzlan A, Bardet S, Belleannée G, Crinière L, Do Cao C, Fouilloux G & Guyetant S et al. 2017 Molecular pathology of anaplastic thyroid carcinomas: a retrospective study of 144 cases. Thyroid 27 682692. (https://doi.org/10.1089/thy.2016.0254)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Cabanillas ME, Zafereo M, Gunn GB & Ferrarotto R 2016 Anaplastic thyroid carcinoma: treatment in the age of molecular targeted therapy. Journal of Oncology Practice 12 511518. (https://doi.org/10.1200/JOP.2016.012013)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Capdevila J, Wirth LJ, Ernst T, Ponce Aix S, Lin CC, Ramlau R, Butler MO, Delord JP, Gelderblom H & Ascierto PA et al. 2020 PD-1 blockade in anaplastic thyroid carcinoma. Journal of Clinical Oncology 38 26202627. (https://doi.org/10.1200/JCO.19.02727)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Cerami E, Gao J, Dogrusoz U, Gross BE, Sumer SO, Aksoy BA, Jacobsen A, Byrne CJ, Heuer ML & Larsson E et al. 2012 The cBio cancer genomics portal: an open platform for exploring multidimensional cancer genomics data. Cancer Discovery 2 401404. (https://doi.org/10.1158/2159-8290.CD-12-0095)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Chen H, Luthra R, Routbort MJ, Patel KP, Cabanillas ME, Broaddus RR & Williams MD 2018 Molecular profile of advanced thyroid carcinomas by next-generation sequencing: characterizing tumors Beyond diagnosis for targeted therapy. Molecular Cancer Therapeutics 17 15751584. (https://doi.org/10.1158/1535-7163.MCT-17-0871)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • De Crevoisier R, Baudin E, Bachelot A, Leboulleux S, Travagli JP, Caillou B & Schlumberger M 2004 Combined treatment of anaplastic thyroid carcinoma with surgery, chemotherapy, and hyperfractionated accelerated external radiotherapy. International Journal of Radiation Oncology, Biology, Physics 60 11371143. (https://doi.org/10.1016/j.ijrobp.2004.05.032)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, Dancey J, Arbuck S, Gwyther S & Mooney M 2009 New response evaluation criteria in solid tumours: revised RECIST guideline, 1.1 version. European Journal of Cancer 45 228247. (https://doi.org/10.1016/j.ejca.2008.10.026)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Gao J, Aksoy BA, Dogrusoz U, Dresdner G, Gross B, Sumer SO, Sun Y, Jacobsen A, Sinha R & Larsson E et al. 2013 Integrative analysis of complex cancer genomics and clinical profiles using the cBioPortal. Science Signaling 6 pl1. (https://doi.org/10.1126/scisignal.2004088)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Gauchotte G, Philippe C, Lacomme S, Léotard B, Wissler MP, Allou L, Toussaint B, Klein M, Vignaud JM & Bressenot A 2011 BRAF, p53 and SOX2 in anaplastic thyroid carcinoma: evidence for multistep carcinogenesis. Pathology 43 447452. (https://doi.org/10.1097/PAT.0b013e3283486178)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Guerra A, Di Crescenzo V, Garzi A, Cinelli M, Carlomagno C, Tonacchera M, Zeppa P & Vitale M 2013 Genetic mutations in the treatment of anaplastic thyroid cancer: a systematic review. BMC Surgery 13 (Supplement 2) S44. (https://doi.org/10.1186/1471-2482-13-S2-S44)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Iñiguez-Ariza NM, Ryder MM, Hilger CR & Bible KC 2017 Salvage lenvatinib therapy in metastatic anaplastic thyroid cancer. Thyroid 27 923927. (https://doi.org/10.1089/thy.2016.0627)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Iwasaki H, Yamazaki H, Takasaki H, Suganuma N, Nakayama H, Toda S & Masudo K 2018 Lenvatinib as a novel treatment for anaplastic thyroid cancer: a retrospective study. Oncology Letters 16 72717277. (https://doi.org/10.3892/ol.2018.9553)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Iwasaki H, Toda S, Suganuma N, Murayama D, Nakayama H & Masudo K 2020 Lenvatinib vs. palliative therapy for stage IVC anaplastic thyroid cancer. Molecular and Clinical Oncology 12 138143. (https://doi.org/10.3892/mco.2019.1964)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Iyer PC, Dadu R, Ferrarotto R, Busaidy NL, Habra MA, Zafereo M, Gross N, Hess KR, Gule-Monroe M & Williams MD et al. 2018 Real-world experience with targeted therapy for the treatment of anaplastic thyroid carcinoma. Thyroid 28 7987. (https://doi.org/10.1089/thy.2017.0285)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Kanazawa S & Kammori M 2019 84-month disease-free survival after surgery for anaplastic thyroid carcinoma. Journal of Nippon Medical School 86 3842. (https://doi.org/10.1272/jnms.JNMS.2019_86-7)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Koyama S, Miyake N, Fujiwara K, Morisaki T, Fukuhara T, Kitano H & Takeuchi H 2018 Lenvatinib for anaplastic thyroid cancer and lenvatinib-induced thyroid dysfunction. European Thyroid Journal 7 139144. (https://doi.org/10.1159/000485972)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Lamartina L, Ippolito S, Danis M, Bidault F, Borget I, Berdelou A, Al Ghuzlan A, Hartl D, Blanchard P & Terroir M et al. 2016 Antiangiogenic tyrosine kinase inhibitors: occurrence and risk factors of hemoptysis in refractory thyroid cancer. Journal of Clinical Endocrinology and Metabolism 101 27332741. (https://doi.org/10.1210/jc.2015-4391)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Landa I, Ibrahimpasic T, Boucai L, Sinha R, Knauf JA, Shah RH, Dogan S, Ricarte-Filho JC, Krishnamoorthy GP & Xu B et al.2016 Genomic and transcriptomic hallmarks of poorly differentiated and anaplastic thyroid cancers. Journal of Clinical Investigation 126 10521066. (https://doi.org/10.1172/JCI85271)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Locati LD, Piovesan A, Durante C, Bregni M, Castagna MG, Zovato S, Giusti M, Ibrahim T, Puxeddu E & Fedele G et al. 2019 Real-world efficacy and safety of lenvatinib: data from a compassionate use in the treatment of radioactive iodine-refractory differentiated thyroid cancer patients in Italy. European Journal of Cancer 118 3540. (https://doi.org/10.1016/j.ejca.2019.05.031)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Ohkubo JI, Takahashi A, Ikezaki S, Takenaga F, Ohkubo Y & Suzuki H 2018 Anaplastic thyroid carcinoma treated with lenvatinib. Kurume Medical Journal 64 2933. (https://doi.org/10.2739/kurumemedj.MS6406)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Oishi K, Takabatake D & Shibuya Y 2017 Efficacy of lenvatinib in a patient with anaplastic thyroid cancer. Endocrinology, Diabetes and Metabolism Case Reports 2017 160136. (https://doi.org/10.1530/EDM-16-0136)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Okamura R, Boichard A, Kato S, Sicklick JK, Bazhenova L & Kurzrock R 2018 Analysis of NTRK alterations in pan-cancer adult and pediatric malignancies: implications for NTRK-targeted therapeutics. JCO Precision Oncology 2018 [epub]. (https://doi.org/10.1200/PO.18.00183)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Pozdeyev N, Gay LM, Sokol ES, Hartmaier R, Deaver KE, Davis S, French JD, Borre PV, LaBarbera DV, Tan AC. 2018 Genetic analysis of 779 advanced differentiated and anaplastic thyroid cancers. Clinical Cancer Research 24 30593068. (https://doi.org/10.1158/1078-0432.CCR-18-0373)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Prasongsook N, Kumar A, Chintakuntlawar AV, Foote RL, Kasperbauer J, Molina J, Garces Y, Ma D, Wittich MAN & Rubin J et al. 2017 Survival in response to multimodal therapy in anaplastic thyroid cancer. Journal of Clinical Endocrinology and Metabolism 102 45064514. (https://doi.org/10.1210/jc.2017-01180)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Romei C, Tacito A, Molinaro E, Piaggi P, Cappagli V, Pieruzzi L, Matrone A, Viola D, Agate L & Torregrossa L et al. 2018 Clinical, pathological and genetic features of anaplastic and poorly differentiated thyroid cancer: a single institute experience. Oncology Letters 15 91749182. (https://doi.org/10.3892/ol.2018.8470)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Schlumberger M, Tahara M, Wirth LJ, Robinson B, Brose MS, Elisei R, Habra MA, Newbold K, Shah MH & Hoff AO et al. 2015 Lenvatinib versus placebo in radioiodine-refractory thyroid cancer. New England Journal of Medicine 372 621630. (https://doi.org/10.1056/NEJMoa1406470)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Smallridge RC, Ain KB, Asa SL, Bible KC, Brierley JD, Burman KD, Kebebew E, Lee NY, Nikiforov YE & Rosenthal MS et al. 2012 American Thyroid Association guidelines for management of patients with anaplastic thyroid cancer. Thyroid 22 11041139. (https://doi.org/10.1089/thy.2012.0302)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Subbiah V, Kreitman RJ, Wainberg ZA, Cho JY, Schellens JHM, Soria JC, Wen PY, Zielinski C, Cabanillas ME & Urbanowitz G et al. 2018 Dabrafenib and trametinib treatment in patients with locally advanced or metastatic BRAF V600-mutant anaplastic thyroid cancer. Journal of Clinical Oncology 36 713. (https://doi.org/10.1200/JCO.2017.73.6785)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Tahara M, Kiyota N, Yamazaki T, Chayahara N, Nakano K, Inagaki L, Toda K, Enokida T, Minami H & Imamura Y et al. 2017 Lenvatinib for anaplastic thyroid cancer. Frontiers in Oncology 7 25. (https://doi.org/10.3389/fonc.2017.00025)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Takahashi S, Kiyota N, Yamazaki T, Chayahara N, Nakano K, Inagaki L, Toda K, Enokida T, Minami H & Imamura Y et al. 2019 A Phase II study of the safety and efficacy of lenvatinib in patients with advanced thyroid cancer. Future Oncology 15 717726. (https://doi.org/10.2217/fon-2018-0557)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Wirth LJ, Eigendorff E, Capdevila J, Paz-Ares LG, Lin C-C, Taylor MH, Ramlau R, Butler M, Delord J-P & Horvath Z et al. 2018 Phase I/II study of spartalizumab (PDR001), an anti-PD1 mAb, in patients with anaplastic thyroid cancer. Journal of Clinical Oncology 36 60246024. (https://doi.org/10.1200/JCO.2018.36.15_suppl.6024)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Wirth LJ, Brose MS, Sherman EJ, Misir S, Xie S, Almonte A, Ye W, Licitra L, Schlumberger M & Sherman SI et al. 2020 MON-521 an open-label, single-arm, multicenter, phase 2 trial of lenvatinib (LEN) for the treatment of anaplastic thyroid cancer (ATC). Journal of the Endocrine Society 4 (Supplement 1) MON-521. (https://doi.org/10.1210/jendso/bvaa046.002)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Yamazaki H, Shimizu S, Iwasaki H, Yoshida T, Suganuma N, Yamanaka T, Kojima I, Masudo K, Toda S & Nakayama H et al. 2017 Efficacy and safety of lenvatinib for unresectable anaplastic thyroid cancer. Cancer and Chemotherapy 44 695697.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Yamazaki H, Iwasaki H, Yamashita T, Yoshida T, Suganuma N, Yamanaka T, Masudo K, Nakayama H, Kohagura K & Rino Y et al. 2018 A case of pneumothorax after treatment with lenvatinib for anaplastic thyroid cancer with lung metastasis. Case Reports in Endocrinology 2018 7875929. (https://doi.org/10.1155/2018/7875929)

    • PubMed
    • Search Google Scholar
    • Export Citation