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Continuous sunitinib schedule in advanced platinum refractory thymic epithelial neoplasms: A retrospective analysis from the ThYmic MalignanciEs (TYME) Italian collaborative group

Published:August 12, 2022DOI:https://doi.org/10.1016/j.ejca.2022.07.009

      Highlights

      • Intermittent sunitinib is used in platinum-refractory thymic epithelial tumours.
      • Continuous daily dose (CDD) sunitinib is used other cancers; no data exist in thymic epithelial tumours.
      • We retrospectively analysed data from patients receiving off-label CDD sunitinib.
      • CDD sunitinib schedule showed clinical efficacy and a favourable toxicity profile.

      Abstract

      Background

      Thymic epithelial tumors (TETs) are rare diseases, with diverse clinical behaviour and prognosis. Intermittent dosing sunitinib represents the gold-standard systemic treatment following platinum-based chemotherapy. To ensure more homogeneous drug exposure, continuous daily dosing (CDD) sunitinib is utilised in other malignancies; however, no data exist in patients with TETs.

      Methods

      We retrospectively examined data from patients with platinum-resistant TETs receiving CDD sunitinib 37.5 mg between 1 May 2017 and 31 May 2022 within the Italian collaborative group for ThYmic MalignanciEs. Primary end-points were median progression-free survival, overall response rate (ORR), median duration of response and major treatment-related adverse events.

      Results

      A total of 20 consecutive patients (12 thymic carcinoma [TC], 6 B3, and 2 B2 thymoma) were evaluated. Among the 19 patients evaluable for response, ORR was 31.6% (95% CI, 12.5%–56.5%). Among patients with TC, one complete response, four partial responses, and four stable diseases were observed (ORR 41%).The overall median progression-free survival was 7.3 months (95% CI, 4.5–10.3): 7.3 months (95% CI, 4.4–NA) within patients with thymoma and 6.8 months (95% CI, 2.8–10.3) in patients with TC; median duration of response was 10.3 months (95% CI, 2.8–NA). CDD was associated with a manageable toxicity profile. Six patients (30%) experienced >G2 toxicity, nine required dose reduction and three discontinued treatment due to adverse events.

      Conclusions

      CDD sunitinib showed a relevant antitumor activity and confirmed a good toxicity profile. Similar effectiveness and a better toxicity profile as compared with intermittent dosing historical data suggest that this schedule should be considered.

      Keywords

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      References

        • Imbimbo M.
        • Ottaviano M.
        • Vitali M.
        • Fabbri A.
        • Leuzzi G.
        • Fiore M.
        • et al.
        Best practices for the management of thymic epithelial tumors: a position paper by the Italian collaborative group for ThYmic MalignanciEs (TYME).
        Cancer Treat Rev. 2018 Dec; 71: 76-87
        • Ahmad U.
        The eighth edition TNM stage classification for thymic tumors: what do I need to know?.
        J Thorac Cardiovasc Surg. 2021 Apr 1; 161: 1524-1529
        • Ruffini E.
        • Fang W.
        • Guerrera F.
        • Huang J.
        • Okumura M.
        • Kim D.K.
        • et al.
        The international association for the study of lung cancer thymic tumors staging project: the impact of the eighth edition of the union for international cancer control and American Joint Committee on cancer TNM stage classification of thymic tumors.
        J Thorac Oncol. 2020 Mar; 15: 436-447
        • Benitez J.C.
        • Besse B.
        Narrative review of immunotherapy in thymic malignancies.
        Transl Lung Cancer Res. 2021 Jun; 10: 3001-3013
        • Cimpean A.M.
        • Raica M.
        • Encica S.
        • Cornea R.
        • Bocan V.
        Immunohistochemical expression of vascular endothelial growth factor A (VEGF), and its receptors (VEGFR1, 2) in normal and pathologic conditions of the human thymus.
        Ann Anat. 2008; 190: 238-245
        • Lattanzio R.
        • La Sorda R.
        • Facciolo F.
        • Sioletic S.
        • Lauriola L.
        • Martucci R.
        • et al.
        Thymic epithelial tumors express vascular endothelial growth factors and their receptors as potential targets of antiangiogenic therapy: a tissue micro array-based multicenter study.
        Lung Cancer. 2014 Aug; 85: 191-196
        • Tomita M.
        • Matsuzaki Y.
        • Edagawa M.
        • Maeda M.
        • Shimizu T.
        • Hara M.
        • et al.
        Correlation between tumor angiogenesis and invasiveness in thymic epithelial tumors.
        J Thorac Cardiovasc Surg. 2002 Sep; 124: 493-498
        • Finke J.H.
        • Rini B.
        • Ireland J.
        • Rayman P.
        • Richmond A.
        • Golshayan A.
        • et al.
        Sunitinib reverses type-1 immune suppression and decreases T-regulatory cells in renal cell carcinoma patients.
        Clin Cancer Res. 2008 Oct 15; 14: 6674-6682
        • Ozao-Choy J.
        • Ma G.
        • Kao J.
        • Wang G.X.
        • Meseck M.
        • Sung M.
        • et al.
        The novel role of tyrosine kinase inhibitor in the reversal of immune suppression and modulation of tumor microenvironment for immune-based cancer therapies.
        Cancer Res. 2009 Mar 15; 69: 2514-2522
        • Sato J.
        • Satouchi M.
        • Itoh S.
        • Okuma Y.
        • Niho S.
        • Mizugaki H.
        • et al.
        Lenvatinib in patients with advanced or metastatic thymic carcinoma (REMORA): a multicentre, phase 2 trial.
        Lancet Oncol. 2020 Jun; 21: 843-850
        • Thomas A.
        • Rajan A.
        • Berman A.
        • Tomita Y.
        • Brzezniak C.
        • Lee M.J.
        • et al.
        Sunitinib in patients with chemotherapy-refractory thymoma and thymic carcinoma: an open-label phase 2 trial.
        Lancet Oncol. 2015 Feb; 16: 177-186
        • Remon J.
        • Girard N.
        • Mazieres J.
        • Dansin E.
        • Pichon E.
        • Greillier L.
        • et al.
        Sunitinib in patients with advanced thymic malignancies: cohort from the French RYTHMIC network.
        Lung Cancer. 2016 Jul; 97: 99-104
        • Mulet-Margalef N.
        • Garcia-Del-Muro X.
        Sunitinib in the treatment of gastrointestinal stromal tumor: patient selection and perspectives.
        Onco Targets Ther. 2016; 9: 7573-7582
        • Blay J.Y.
        Pharmacological management of gastrointestinal stromal tumours: an update on the role of sunitinib.
        Ann Oncol. 2010 Feb; 21: 208-215
        • Houk B.E.
        • Bello C.L.
        • Poland B.
        • Rosen L.S.
        • Demetri G.D.
        • Motzer R.J.
        Relationship between exposure to sunitinib and efficacy and tolerability endpoints in patients with cancer: results of a pharmacokinetic/pharmacodynamic meta-analysis.
        Cancer Chemother Pharmacol. 2010 Jul; 66: 357-371
        • Escudier B.
        • Roigas J.
        • Gillessen S.
        • Harmenberg U.
        • Srinivas S.
        • Mulder S.F.
        • et al.
        Phase II study of sunitinib administered in a continuous once-daily dosing regimen in patients with cytokine-refractory metastatic renal cell carcinoma.
        J Clin Oncol. 2009 Sep 1; 27: 4068-4075
        • Lee J.L.
        • Kim M.K.
        • Park I.
        • Ahn J.H.
        • Lee D.H.
        • Ryoo H.M.
        • et al.
        RandomizEd phase II trial of Sunitinib four weeks on and two weeks off versus Two weeks on and One week off in metastatic clear-cell type REnal cell carcinoma: RESTORE trial.
        Ann Oncol. 2015 Nov; 26: 2300-2305
        • Bracarda S.
        • Iacovelli R.
        • Boni L.
        • Rizzo M.
        • Derosa L.
        • Rossi M.
        • et al.
        Sunitinib administered on 2/1 schedule in patients with metastatic renal cell carcinoma: the RAINBOW analysis.
        Ann Oncol. 2016 Feb; 27: 366
        • Barrios C.H.
        • Hernandez-Barajas D.
        • Brown M.P.
        • Lee S.H.
        • Fein L.
        • Liu J.H.
        • et al.
        Phase II trial of continuous once-daily dosing of sunitinib as first-line treatment in patients with metastatic renal cell carcinoma.
        Cancer. 2012 Mar 1; 118: 1252-1259
        • Motzer R.J.
        • Hutson T.E.
        • Olsen M.R.
        • Hudes G.R.
        • Burke J.M.
        • Edenfield W.J.
        • et al.
        Randomized phase II trial of sunitinib on an intermittent versus continuous dosing schedule as first-line therapy for advanced renal cell carcinoma.
        J Clin Oncol. 2012 Apr 20; 30: 1371-1377
        • George S.
        • Blay J.Y.
        • Casali P.G.
        • Le Cesne A.
        • Morgan J.A.
        • Pokela J.
        • et al.
        Continuous daily dosing (CDD) of sunitinib malate (SU) compares favorably with intermittent dosing in pts with advanced GIST.
        J Clin Orthod. 2007 Jun 20; 25 (10015–10015)
        • George S.
        • Blay J.Y.
        • Casali P.G.
        • Le Cesne A.
        • Stephenson P.
        • DePrimo S.E.
        • et al.
        Clinical evaluation of continuous daily dosing of sunitinib malate in patients with advanced gastrointestinal stromal tumour after imatinib failure.
        Eur J Cancer. 2009 Jul 1; 45: 1959-1968