Effectiveness and toxicity of lenvatinib in refractory thyroid cancer: Dutch real-life data

in European Journal of Endocrinology

Correspondence should be addressed to J Zwaveling; Email: J.Zwaveling@lumc.nl
Restricted access

Objective

The SELECT trial showed progression-free survival (PFS) benefit for lenvatinib for advanced radioiodine-refractory differentiated thyroid cancer (RAI-refractory or RR-DTC) patients, on which current clinical practice is based. We assessed whether the effectiveness and toxicity of lenvatinib in real-life clinical practice in the Netherlands were comparable to the pivotal SELECT trial.

Methods

From three Dutch centres Electronic Health Records (EHRs) of patients treated in the lenvatinib compassionate use program or as standard of care were reviewed and checked for SELECT eligibility criteria. Baseline characteristics, safety, and efficacy measures were compared and PFS and overall survival (OS) were calculated. Furthermore, PFS was compared to estimates of PFS reported in other studies.

Results

A total of 39 DTC patients with a median age of 62 years were analysed. Of these, 27 patients (69%) did not fulfil the SELECT eligibility criteria. The most common grade ≥3 toxicities were hypertension (n = 11, 28%), diarrhoea (n = 7, 18%), vomiting (n = 4, 10%), and gallbladder disease (n = 3, 8%). Median PFS and median OS were 9.7 (95% confidence interval (CI): 4.0–15.5) and 18.3 (95% CI: 4.9–31.7) months, respectively, response rate was 38% (95% CI: 23–54%). PFS in the Dutch real-life situation was comparable to previous real-life studies, but inferior to PFS as shown in the SELECT trial (P = 0.04).

Conclusions

PFS in our non-trial population was significantly shorter than in the SELECT trial population. In the interpretation of results, differences in the real-life population and the SELECT study population regarding patient characteristics should be taken into account.

 

     European Society of Endocrinology

Sept 2018 onwards Past Year Past 30 Days
Abstract Views 985 985 227
Full Text Views 111 111 8
PDF Downloads 71 71 4
  • 1

    LimHDevesaSSSosaJACheckDKitaharaCM. Trends in thyroid cancer incidence and mortality in the United States, 1974–2013. JAMA 2017 13381348. (https://doi.org/10.1001/jama.2017.2719)

    • Search Google Scholar
    • Export Citation
  • 2

    Lloyd RV Osamura RY Klöppel G & Rosai J. WHO Classification of Tumours of Endocrine Organs Vol. 10 4th ed. Lyon: International Agency for Research on Cancer 2017.

    • Search Google Scholar
    • Export Citation
  • 3

    HaugenBRAlexanderEKBibleKCDohertyGMMandelSJNikiforovYEPaciniFRandolphGWSawkaAMSchlumbergerM 2015 American Thyroid Association management guidelines for adult patients with thyroid nodules and differentiated thyroid cancer: the American Thyroid Association Guidelines Task Force on thyroid nodules and differentiated thyroid cancer. Thyroid 2016 1133. (https://doi.org/10.1089/thy.2015.0020)

    • Search Google Scholar
    • Export Citation
  • 4

    SchlumbergerMBroseMEliseiRLeboulleuxSLusterMPitoiaFPaciniF. Definition and management of radioactive iodine-refractory differentiated thyroid cancer. Lancet: Diabetes and Endocrinology 2014 356358. (https://doi.org/10.1016/S2213-8587(13)70215-8)

    • Search Google Scholar
    • Export Citation
  • 5

    DuranteCHaddyNBaudinELeboulleuxSHartlDTravagliJPCaillouBRicardMLumbrosoJDDe VathaireF Long-term outcome of 444 patients with distant metastases from papillary and follicular thyroid carcinoma: benefits and limits of radioiodine therapy. Journal of Clinical Endocrinology and Metabolism 2006 28922899. (https://doi.org/10.1210/jc.2005-2838)

    • Search Google Scholar
    • Export Citation
  • 6

    BroseMSSmitJCapdevilaJEliseiRNuttingCPitoiaFRobinsonBSchlumbergerMShongYKTakamiH. Regional approaches to the management of patients with advanced, radioactive iodine-refractory differentiated thyroid carcinoma. Expert Review of Anticancer Therapy 2012 11371147. (https://doi.org/10.1586/era.12.96)

    • Search Google Scholar
    • Export Citation
  • 7

    SchlumbergerMTaharaMWirthLJRobinsonBBroseMSEliseiRHabraMANewboldKShahMHHoffAO Lenvatinib versus placebo in radioiodine-refractory thyroid cancer. New England Journal of Medicine 2015 621630. (https://doi.org/10.1056/NEJMoa1406470)

    • Search Google Scholar
    • Export Citation
  • 8

    AgrawalVRJodonGMushtagRBowlesDW. Update on multikinase inhibitor therapy for differentiated thyroid cancer. Drugs of Today 2018 535545. (https://doi.org/10.1358/dot.2018.54.9.2878150)

    • Search Google Scholar
    • Export Citation
  • 9

    ZschäbitzSGrüllichC. Lenvantinib: a tyrosine kinase inhibitor of VEGFR 1–3, FGFR 1–4, PDGFRalpha, KIT and RET. Recent Results in Cancer Research 2018 187198.

    • Search Google Scholar
    • Export Citation
  • 10

    GianoukakisAGDutcusCEBattyNGuoMBaigM. Prolonged duration of response in lenvatinib responders with thyroid cancer. Endocrine-Related Cancer 2018 699704. (https://doi.org/10.1530/ERC-18-0049)

    • Search Google Scholar
    • Export Citation
  • 11

    BerdelouABorgetIGodbertYNguyenTGarciaMEChougnetCNFerruABuffetCChabreOHuillardO Lenvatinib for the treatment of radioiodine-refractory thyroid cancer in real-life practice. Thyroid 2017 7278. (https://doi.org/10.1089/thy.2017.0205)

    • Search Google Scholar
    • Export Citation
  • 12

    BalmelliCRailicNSianoMFeuerleinKCathomasRCristinaVGuthnerCZimmermanSWeidnerSPlessM Lenvatinib in advanced radioiodine-refractory thyroid cancer – a retrospective analysis of the Swiss lenvatinib named patient program. Journal of Cancer 2018 250255. (https://doi.org/10.7150/jca.22318)

    • Search Google Scholar
    • Export Citation
  • 13

    NervoAGalloMSamaMTFelicettiFAlfanoMMiglioreEMarchisioFBerardelliRArvatEPiovesanA. Lenvatinib in advanced radioiodine-refractory thyroid cancer: a snapshot of real-life clinical practice. Anticancer Research 2018 16431649. (https://doi.org/10.21873/anticanres.12396)

    • Search Google Scholar
    • Export Citation
  • 14

    SuginoKNagahamaMKitagawaWOhkuwaKUrunoTMatsuzuKSuzukiAMasakiCAkaishiJHamesKY Clinical factors related to the efficacy of tyrosine kinase inhibitor therapy in radioactive iodine refractory recurrent differentiated thyroid cancer patients. Endocrine Journal 2018 299306. (https://doi.org/10.1507/endocrj.EJ17-0365)

    • Search Google Scholar
    • Export Citation
  • 15

    SimonR. Confidence intervals for reporting results of clinical trials. Annals of Internal Medicine 1986 429435. (https://doi.org/10.7326/0003-4819-105-3-429)

    • Search Google Scholar
    • Export Citation
  • 16

    BerdelouALamartinaLKlainMLeboulleuxSSchlumberger & TUTHTYREF Network. Treatment of refractory thyroid cancer. Endocrine-Related Cancer 2018 209223.

    • Search Google Scholar
    • Export Citation
  • 17

    YuSTGeJNLuoJYWeiZGSunBHLeiST. Treatment-related adverse effects with TKIs in patients with advanced or radioiodine refractory differentiated thyroid carcinoma: a systematic review and meta-analysis. Cancer Management and Research 2019 15251532. (https://doi.org/10.2147/CMAR.S191499)

    • Search Google Scholar
    • Export Citation
  • 18

    HayatoSShumakerRFerryJBinderTDutcusCEHusseinZ. Exposure-response analysis and simulation of lenvatinib safety and efficacy in patients with radioiodine-refractory differentiated thyroid cancer. Cancer Chemotherapy and Pharmacology 2018 971978. (https://doi.org/10.1007/s00280-018-3687-4)

    • Search Google Scholar
    • Export Citation
  • 19

    CabanillasMETakahashiS. Managing the adverse events associated with lenvatinib therapy in radioiodine-refractory differentiated thyroid cancer. Seminars in Oncology 2019 5764. (https://doi.org/10.1053/j.seminoncol.2018.11.004)

    • Search Google Scholar
    • Export Citation
  • 20

    ResteghiniCCavalieriSGalbiatiDGranataRAlfieriSBergaminiCBossiPLicitraLLocatiLD. Management of tyrosine kinase inhibitors (TKI) side effects in differentiated and medullary thyroid cancer patients. Best Practice and Research: Clinical Endocrinology and Metabolism 2017 349361. (https://doi.org/10.1016/j.beem.2017.04.012)

    • Search Google Scholar
    • Export Citation
  • 21

    YamazakiHIwasakiHTakasakiHSuganumaNSakaiRMasudoKNakayamaHRinoYMasudaM. Efficacy and tolerability of initial low-dose lenvatinib to treat differentiated thyroid cancer. Medicine 2019 e14774. (https://doi.org/10.1097/MD.0000000000014774)

    • Search Google Scholar
    • Export Citation
  • 22

    CapdevilaJNewboldKLicitraLPopovtzerAMoresoFZamoranoJKreisslMAllerJGrandeE. Optimisation of treatment with lenvatinib in radioactive iodine-refractory differentiated thyroid cancer. Cancer Treatment Reviews 2018 164176. (https://doi.org/10.1016/j.ctrv.2018.06.019)

    • Search Google Scholar
    • Export Citation
  • 23

    TaharaMBroseMSWirthLJSuzukiTMiyagishiHFujinoKDutcusCEGianoukakisA. Impact of dose interruption on the efficacy of lenvatinib in a phase 3 study in patients with radioiodine-refractory differentiated thyroid cancer. European Journal of Cancer 2019 6168. (https://doi.org/10.1016/j.ejca.2018.10.002)

    • Search Google Scholar
    • Export Citation
  • 24

    WirthLJTaharaMRobinsonBFrancisSBroseMSHabraMANewboldKKiyotaNDutcusCEMathiasE Treatment-emergent hypertension and efficacy in the phase 3 study of (E7080) lenvatinib in differentiated cancer of the thyroid (SELECT). Cancer 2018 23652372. (https://doi.org/10.1002/cncr.31344)

    • Search Google Scholar
    • Export Citation
  • 25

    BudolfsenCFaberJGrimmDKrugerMBauerJWehlandMInfangerMMagnussonNE. Tyrosine kinase inhibitor-induced hypertension: role of hypertension as a biomarker in cancer treatment. Current Vascular Pharmacology 2019 618634. (https://doi.org/10.2174/1570161117666190130165810)

    • Search Google Scholar
    • Export Citation
  • 26

    CalifanoIDeutschSLowensteinACabezonCPitoiaF. Outcomes of patients with bone metastases from differentiated thyroid cancer. Archives of Endocrinology and Metabolism 2018 1420. (https://doi.org/10.20945/2359-3997000000004)

    • Search Google Scholar
    • Export Citation