Trabectedin monotherapy after standard chemotherapy versus best supportive care in patients with advanced, translocation-related sarcoma

A randomised, open-label, phase 2 study

Akira Kawai, Nobuhito Araki, Hideshi Sugiura, Takafumi Ueda, Tsukasa Yonemoto, Mitsuru Takahashi, Hideo Morioka, Hiroaki Hiraga, Toru Hiruma, Toshiyuki Kunisada, Akihiko Matsumine, Takanori Tanase, Tadashi Hasegawa, Shunji Takahashi

Research output: Contribution to journalArticle

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Abstract

Background: Trabectedin binds to the minor groove of DNA and blocks DNA repair machinery. Preclinical data have shown that trabectedin also modulates the transcription of the oncogenic fusion proteins of translocation-related sarcomas. We aimed to assess the efficacy and safety of trabectedin as second-line therapy or later for patients with advanced translocation-related sarcoma. Methods: We did a multicentre randomised open-label study in Japan. Eligible patients had pathological diagnosis of translocation-related sarcoma, were aged 19 years or older, were unresponsive or intolerant to standard chemotherapy regimens, no more than four previous chemotherapy regimens, Eastern Cooperative Oncology Group performance status 0 or 1, adequate bone marrow reserve, renal and liver functions, and had measurable lesions. Patients were randomly assigned (1:1) by the minimisation method to receive either trabectedin (1.2 mg/m2 given via a central venous line over 24 h on day 1 of a 21 day treatment cycle) or best supportive care, which was adjusted centrally by pathological subtype. Investigators, patients, and the sponsor were unmasked to the treatment assignment. Progression-free survival and objective responses were assessed by a masked central radiology imaging review. Efficacy was assessed by masked central radiology imaging review. The primary endpoint was progression-free survival for the full analysis set population. Follow-up is ongoing for the patients under study treatment. The study is registered with Japan Pharmaceutical Information Center, number JapicCTI-121850. Findings: Between July 11, 2012, and Jan 20, 2014, 76 patients were enrolled and allocated to receive either trabectedin (n=39) or best supportive care (n=37). After central review to confirm pathological subtypes, 73 patients (37 in the trabectedin group and 36 in the best supportive care group) were included in the primary efficacy analysis. Median progression-free survival of the trabectedin group was 5.6 months (95% CI 4.1-7.5) and the best supportive care group was 0.9 months (0.7-1.0). The hazard ratio (HR) for progression-free survival of trabectedin versus best supportive care was 0.07 (90% CI 0.03-0.14 and 95% CI 0.03-0.16) by a Cox proportional hazards model (p

Original languageEnglish
Pages (from-to)406-416
Number of pages11
JournalThe Lancet Oncology
Volume16
Issue number4
DOIs
Publication statusPublished - 2015

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trabectedin
Sarcoma
Patient Care
Drug Therapy
Disease-Free Survival
Radiology
Japan
Information Centers
Protein Transport
Therapeutics
Survival Analysis
Proportional Hazards Models

ASJC Scopus subject areas

  • Oncology
  • Medicine(all)

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Trabectedin monotherapy after standard chemotherapy versus best supportive care in patients with advanced, translocation-related sarcoma : A randomised, open-label, phase 2 study. / Kawai, Akira; Araki, Nobuhito; Sugiura, Hideshi; Ueda, Takafumi; Yonemoto, Tsukasa; Takahashi, Mitsuru; Morioka, Hideo; Hiraga, Hiroaki; Hiruma, Toru; Kunisada, Toshiyuki; Matsumine, Akihiko; Tanase, Takanori; Hasegawa, Tadashi; Takahashi, Shunji.

In: The Lancet Oncology, Vol. 16, No. 4, 2015, p. 406-416.

Research output: Contribution to journalArticle

Kawai, A, Araki, N, Sugiura, H, Ueda, T, Yonemoto, T, Takahashi, M, Morioka, H, Hiraga, H, Hiruma, T, Kunisada, T, Matsumine, A, Tanase, T, Hasegawa, T & Takahashi, S 2015, 'Trabectedin monotherapy after standard chemotherapy versus best supportive care in patients with advanced, translocation-related sarcoma: A randomised, open-label, phase 2 study', The Lancet Oncology, vol. 16, no. 4, pp. 406-416. https://doi.org/10.1016/S1470-2045(15)70098-7
Kawai, Akira ; Araki, Nobuhito ; Sugiura, Hideshi ; Ueda, Takafumi ; Yonemoto, Tsukasa ; Takahashi, Mitsuru ; Morioka, Hideo ; Hiraga, Hiroaki ; Hiruma, Toru ; Kunisada, Toshiyuki ; Matsumine, Akihiko ; Tanase, Takanori ; Hasegawa, Tadashi ; Takahashi, Shunji. / Trabectedin monotherapy after standard chemotherapy versus best supportive care in patients with advanced, translocation-related sarcoma : A randomised, open-label, phase 2 study. In: The Lancet Oncology. 2015 ; Vol. 16, No. 4. pp. 406-416.
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T2 - A randomised, open-label, phase 2 study

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AU - Araki, Nobuhito

AU - Sugiura, Hideshi

AU - Ueda, Takafumi

AU - Yonemoto, Tsukasa

AU - Takahashi, Mitsuru

AU - Morioka, Hideo

AU - Hiraga, Hiroaki

AU - Hiruma, Toru

AU - Kunisada, Toshiyuki

AU - Matsumine, Akihiko

AU - Tanase, Takanori

AU - Hasegawa, Tadashi

AU - Takahashi, Shunji

PY - 2015

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N2 - Background: Trabectedin binds to the minor groove of DNA and blocks DNA repair machinery. Preclinical data have shown that trabectedin also modulates the transcription of the oncogenic fusion proteins of translocation-related sarcomas. We aimed to assess the efficacy and safety of trabectedin as second-line therapy or later for patients with advanced translocation-related sarcoma. Methods: We did a multicentre randomised open-label study in Japan. Eligible patients had pathological diagnosis of translocation-related sarcoma, were aged 19 years or older, were unresponsive or intolerant to standard chemotherapy regimens, no more than four previous chemotherapy regimens, Eastern Cooperative Oncology Group performance status 0 or 1, adequate bone marrow reserve, renal and liver functions, and had measurable lesions. Patients were randomly assigned (1:1) by the minimisation method to receive either trabectedin (1.2 mg/m2 given via a central venous line over 24 h on day 1 of a 21 day treatment cycle) or best supportive care, which was adjusted centrally by pathological subtype. Investigators, patients, and the sponsor were unmasked to the treatment assignment. Progression-free survival and objective responses were assessed by a masked central radiology imaging review. Efficacy was assessed by masked central radiology imaging review. The primary endpoint was progression-free survival for the full analysis set population. Follow-up is ongoing for the patients under study treatment. The study is registered with Japan Pharmaceutical Information Center, number JapicCTI-121850. Findings: Between July 11, 2012, and Jan 20, 2014, 76 patients were enrolled and allocated to receive either trabectedin (n=39) or best supportive care (n=37). After central review to confirm pathological subtypes, 73 patients (37 in the trabectedin group and 36 in the best supportive care group) were included in the primary efficacy analysis. Median progression-free survival of the trabectedin group was 5.6 months (95% CI 4.1-7.5) and the best supportive care group was 0.9 months (0.7-1.0). The hazard ratio (HR) for progression-free survival of trabectedin versus best supportive care was 0.07 (90% CI 0.03-0.14 and 95% CI 0.03-0.16) by a Cox proportional hazards model (p

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