Sunitinib in patients with chemotherapy-refractory thymoma and thymic carcinoma: An open-label phase 2 trial

Anish Thomas, Arun Rajan, Arlene Berman, Yusuke Tomita, Christina Brzezniak, Min Jung Lee, Sunmin Lee, Alexander Ling, Aaron J. Spittler, Corey A. Carter, Udayan Guha, Yisong Wang, Eva Szabo, Paul Meltzer, Seth M. Steinberg, Jane B. Trepel, Patrick Loehrer, Giuseppe Giaccone

Research output: Contribution to journalArticle

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Abstract

Background: No standard treatments are available for advanced thymic epithelial tumours after failure of platinum-based chemotherapy. We investigated the activity of sunitinib, an orally administered tyrosine kinase inhibitor. Methods: Between May 15, 2012, and Oct 2, 2013, we did an open-label phase 2 trial in patients with histologically confirmed chemotherapy-refractory thymic epithelial tumours. Patients were eligible if they had disease progression after at least one previous regimen of platinum-containing chemotherapy, an Eastern Cooperative Oncology Group performance status of two or lower, measurable disease, and adequate organ function. Patients received 50 mg of sunitinib orally once a day, in 6-week cycles (ie, 4 weeks of treatment followed by 2 weeks without treatment), until tumour progression or unacceptable toxic effects arose. The primary endpoint was investigator-assessed best tumour response at any point, which we analysed separately in thymoma and thymic carcinoma cohorts. Patients who had received at least one cycle of treatment and had their disease reassessed were included in the analyses of response. The trial was registered with ClinicalTrials.gov, number NCT01621568. Findings: 41 patients were enrolled, 25 with thymic carcinoma and 16 with thymoma. One patient with thymic carcinoma was deemed ineligible after enrolment and did not receive protocol treatment. Of patients who received treatment, one individual with thymic carcinoma was not assessable because she died. Median follow-up on trial was 17 months (IQR 14.0-18.4). Of 23 assessable patients with thymic carcinoma, six (26%, 90% CI 12.1-45.3, 95% CI 10.2-48.4) had partial responses, 15 (65%, 95% CI 42.7-83.6) achieved stable disease, and two (9%, 1.1-28.0) had progressive disease. Of 16 patients with thymoma, one (6%, 95% CI 0.2-30.2) had a partial response, 12 (75%, 47.6-92.7) had stable disease, and three (19%, 4.1-45.7) had progressive disease. The most common grade 3 and 4 treatment-related adverse events were lymphocytopenia (eight [20%] of 40 patients), fatigue (eight [20%]), and oral mucositis (eight [20%]). Five (13%) patients had decreases in left-ventricular ejection fraction, of which three (8%) were grade 3 events. Three (8%) patients died during treatment, including one individual who died of cardiac arrest that was possibly treatment-related. Interpretation: Sunitinib is active in previously treated patients with thymic carcinoma. Further studies are needed to identify potential biomarkers of activity. Funding: National Cancer Institute (Cancer Therapy Evaluation Program).

Original languageEnglish
Pages (from-to)177-186
Number of pages10
JournalThe Lancet Oncology
Volume16
Issue number2
DOIs
StatePublished - Feb 1 2015

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Thymoma
Drug Therapy
Therapeutics
Platinum
sunitinib
Neoplasms
Stomatitis
Lymphopenia
National Cancer Institute (U.S.)
Poisons
Program Evaluation
Clinical Protocols
Heart Arrest
Stroke Volume
Protein-Tyrosine Kinases
Fatigue
Disease Progression

ASJC Scopus subject areas

  • Oncology
  • Medicine(all)

Cite this

Thomas, A., Rajan, A., Berman, A., Tomita, Y., Brzezniak, C., Lee, M. J., ... Giaccone, G. (2015). Sunitinib in patients with chemotherapy-refractory thymoma and thymic carcinoma: An open-label phase 2 trial. The Lancet Oncology, 16(2), 177-186. https://doi.org/10.1016/S1470-2045(14)71181-7

Sunitinib in patients with chemotherapy-refractory thymoma and thymic carcinoma : An open-label phase 2 trial. / Thomas, Anish; Rajan, Arun; Berman, Arlene; Tomita, Yusuke; Brzezniak, Christina; Lee, Min Jung; Lee, Sunmin; Ling, Alexander; Spittler, Aaron J.; Carter, Corey A.; Guha, Udayan; Wang, Yisong; Szabo, Eva; Meltzer, Paul; Steinberg, Seth M.; Trepel, Jane B.; Loehrer, Patrick; Giaccone, Giuseppe.

In: The Lancet Oncology, Vol. 16, No. 2, 01.02.2015, p. 177-186.

Research output: Contribution to journalArticle

Thomas, A, Rajan, A, Berman, A, Tomita, Y, Brzezniak, C, Lee, MJ, Lee, S, Ling, A, Spittler, AJ, Carter, CA, Guha, U, Wang, Y, Szabo, E, Meltzer, P, Steinberg, SM, Trepel, JB, Loehrer, P & Giaccone, G 2015, 'Sunitinib in patients with chemotherapy-refractory thymoma and thymic carcinoma: An open-label phase 2 trial', The Lancet Oncology, vol. 16, no. 2, pp. 177-186. https://doi.org/10.1016/S1470-2045(14)71181-7
Thomas, Anish ; Rajan, Arun ; Berman, Arlene ; Tomita, Yusuke ; Brzezniak, Christina ; Lee, Min Jung ; Lee, Sunmin ; Ling, Alexander ; Spittler, Aaron J. ; Carter, Corey A. ; Guha, Udayan ; Wang, Yisong ; Szabo, Eva ; Meltzer, Paul ; Steinberg, Seth M. ; Trepel, Jane B. ; Loehrer, Patrick ; Giaccone, Giuseppe. / Sunitinib in patients with chemotherapy-refractory thymoma and thymic carcinoma : An open-label phase 2 trial. In: The Lancet Oncology. 2015 ; Vol. 16, No. 2. pp. 177-186.
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author = "Anish Thomas and Arun Rajan and Arlene Berman and Yusuke Tomita and Christina Brzezniak and Lee, {Min Jung} and Sunmin Lee and Alexander Ling and Spittler, {Aaron J.} and Carter, {Corey A.} and Udayan Guha and Yisong Wang and Eva Szabo and Paul Meltzer and Steinberg, {Seth M.} and Trepel, {Jane B.} and Patrick Loehrer and Giuseppe Giaccone",
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T1 - Sunitinib in patients with chemotherapy-refractory thymoma and thymic carcinoma

T2 - An open-label phase 2 trial

AU - Thomas, Anish

AU - Rajan, Arun

AU - Berman, Arlene

AU - Tomita, Yusuke

AU - Brzezniak, Christina

AU - Lee, Min Jung

AU - Lee, Sunmin

AU - Ling, Alexander

AU - Spittler, Aaron J.

AU - Carter, Corey A.

AU - Guha, Udayan

AU - Wang, Yisong

AU - Szabo, Eva

AU - Meltzer, Paul

AU - Steinberg, Seth M.

AU - Trepel, Jane B.

AU - Loehrer, Patrick

AU - Giaccone, Giuseppe

PY - 2015/2/1

Y1 - 2015/2/1

N2 - Background: No standard treatments are available for advanced thymic epithelial tumours after failure of platinum-based chemotherapy. We investigated the activity of sunitinib, an orally administered tyrosine kinase inhibitor. Methods: Between May 15, 2012, and Oct 2, 2013, we did an open-label phase 2 trial in patients with histologically confirmed chemotherapy-refractory thymic epithelial tumours. Patients were eligible if they had disease progression after at least one previous regimen of platinum-containing chemotherapy, an Eastern Cooperative Oncology Group performance status of two or lower, measurable disease, and adequate organ function. Patients received 50 mg of sunitinib orally once a day, in 6-week cycles (ie, 4 weeks of treatment followed by 2 weeks without treatment), until tumour progression or unacceptable toxic effects arose. The primary endpoint was investigator-assessed best tumour response at any point, which we analysed separately in thymoma and thymic carcinoma cohorts. Patients who had received at least one cycle of treatment and had their disease reassessed were included in the analyses of response. The trial was registered with ClinicalTrials.gov, number NCT01621568. Findings: 41 patients were enrolled, 25 with thymic carcinoma and 16 with thymoma. One patient with thymic carcinoma was deemed ineligible after enrolment and did not receive protocol treatment. Of patients who received treatment, one individual with thymic carcinoma was not assessable because she died. Median follow-up on trial was 17 months (IQR 14.0-18.4). Of 23 assessable patients with thymic carcinoma, six (26%, 90% CI 12.1-45.3, 95% CI 10.2-48.4) had partial responses, 15 (65%, 95% CI 42.7-83.6) achieved stable disease, and two (9%, 1.1-28.0) had progressive disease. Of 16 patients with thymoma, one (6%, 95% CI 0.2-30.2) had a partial response, 12 (75%, 47.6-92.7) had stable disease, and three (19%, 4.1-45.7) had progressive disease. The most common grade 3 and 4 treatment-related adverse events were lymphocytopenia (eight [20%] of 40 patients), fatigue (eight [20%]), and oral mucositis (eight [20%]). Five (13%) patients had decreases in left-ventricular ejection fraction, of which three (8%) were grade 3 events. Three (8%) patients died during treatment, including one individual who died of cardiac arrest that was possibly treatment-related. Interpretation: Sunitinib is active in previously treated patients with thymic carcinoma. Further studies are needed to identify potential biomarkers of activity. Funding: National Cancer Institute (Cancer Therapy Evaluation Program).

AB - Background: No standard treatments are available for advanced thymic epithelial tumours after failure of platinum-based chemotherapy. We investigated the activity of sunitinib, an orally administered tyrosine kinase inhibitor. Methods: Between May 15, 2012, and Oct 2, 2013, we did an open-label phase 2 trial in patients with histologically confirmed chemotherapy-refractory thymic epithelial tumours. Patients were eligible if they had disease progression after at least one previous regimen of platinum-containing chemotherapy, an Eastern Cooperative Oncology Group performance status of two or lower, measurable disease, and adequate organ function. Patients received 50 mg of sunitinib orally once a day, in 6-week cycles (ie, 4 weeks of treatment followed by 2 weeks without treatment), until tumour progression or unacceptable toxic effects arose. The primary endpoint was investigator-assessed best tumour response at any point, which we analysed separately in thymoma and thymic carcinoma cohorts. Patients who had received at least one cycle of treatment and had their disease reassessed were included in the analyses of response. The trial was registered with ClinicalTrials.gov, number NCT01621568. Findings: 41 patients were enrolled, 25 with thymic carcinoma and 16 with thymoma. One patient with thymic carcinoma was deemed ineligible after enrolment and did not receive protocol treatment. Of patients who received treatment, one individual with thymic carcinoma was not assessable because she died. Median follow-up on trial was 17 months (IQR 14.0-18.4). Of 23 assessable patients with thymic carcinoma, six (26%, 90% CI 12.1-45.3, 95% CI 10.2-48.4) had partial responses, 15 (65%, 95% CI 42.7-83.6) achieved stable disease, and two (9%, 1.1-28.0) had progressive disease. Of 16 patients with thymoma, one (6%, 95% CI 0.2-30.2) had a partial response, 12 (75%, 47.6-92.7) had stable disease, and three (19%, 4.1-45.7) had progressive disease. The most common grade 3 and 4 treatment-related adverse events were lymphocytopenia (eight [20%] of 40 patients), fatigue (eight [20%]), and oral mucositis (eight [20%]). Five (13%) patients had decreases in left-ventricular ejection fraction, of which three (8%) were grade 3 events. Three (8%) patients died during treatment, including one individual who died of cardiac arrest that was possibly treatment-related. Interpretation: Sunitinib is active in previously treated patients with thymic carcinoma. Further studies are needed to identify potential biomarkers of activity. Funding: National Cancer Institute (Cancer Therapy Evaluation Program).

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