Efficacy of trabectedin in patients with advanced translocation- related sarcomas

Pooled analysis of two phase II studies

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

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Background. Trabectedin is reported as effective, especially against translocation-related sarcomas (TRSs) after failure of or intolerance to standard chemotherapy. We conducted two phase II studies of TRS, confirming high efficacy of 1.2 mg/m2 trabectedin. The updated data of 66 patients in these studies was integrated to evaluate the efficacy of trabectedin against each histological subtype, and analyze final overall survival (OS). Methods. Trabectedin was administered on day one of a 21-day cycle. Efficacy was assessed using progression-free survival (PFS), OS, and best overall response. An analysis of OS and PFS was performed for subgroups divided by baseline lymphocyte count (<1,000/µL,≥µ1,000/lL) or number of previous chemotherapy regimens (0, 1, 2 ≥3 regimens), and a Weibull parametric model was used to estimate the numerical relationship between lymphocyte count and PFS and OS. Results. Median PFS and OS in overall patients were 5.6 (95% confidence interval [CI]: 4.1-7.3) and 17.5 months (95% CI: 12.6-23.6), respectively. PFS in the myxoid and round-cell liposarcoma (MRCL) group (7.4 months [95% CI: 5.6-11.1]) was longer than in the other subtypes. The response rate was also highest in the MRCL group. Median OS was longer in patients with baseline lymphocyte counts ≥1,000/µL than in those with counts of <1,000/µL, but median PFS was not different between the two subgroups. Conclusion. Our updated and pooled data showed that trabectedin exerted prolonged disease control and antitumor effects in patients with advanced TRS, especially in MRCL.We consider that the subgroup analyses also provide important information for trabectedin treatment in patients with TRS.

Original languageEnglish
Pages (from-to)980-988
Number of pages9
JournalOncologist
Volume22
Issue number8
DOIs
Publication statusPublished - Aug 1 2017

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trabectedin
Sarcoma
Disease-Free Survival
Liposarcoma
Lymphocyte Count
Survival
Confidence Intervals
Drug Therapy
Survival Analysis

Keywords

  • Histological subtype
  • Lymphocyte count
  • Number of previous chemotherapy regimen
  • Trabectedin
  • Translocation-related sarcoma

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Takahashi, M., Takahashi, S., Araki, N., Sugiura, H., Ueda, T., Yonemoto, T., ... Kawai, A. (2017). Efficacy of trabectedin in patients with advanced translocation- related sarcomas: Pooled analysis of two phase II studies. Oncologist, 22(8), 980-988. https://doi.org/10.1634/theoncologist.2016-0064

Efficacy of trabectedin in patients with advanced translocation- related sarcomas : Pooled analysis of two phase II studies. / Takahashi, Mitsuru; Takahashi, Shunji; Araki, Nobuhito; Sugiura, Hideshi; Ueda, Takafumi; Yonemoto, Tsukasa; Morioka, Hideo; Hiraga, Hiroaki; Hiruma, Toru; Kunisada, Toshiyuki; Matsumine, Akihiko; Shimura, Masashi; Kawai, Akira.

In: Oncologist, Vol. 22, No. 8, 01.08.2017, p. 980-988.

Research output: Contribution to journalArticle

Takahashi, M, Takahashi, S, Araki, N, Sugiura, H, Ueda, T, Yonemoto, T, Morioka, H, Hiraga, H, Hiruma, T, Kunisada, T, Matsumine, A, Shimura, M & Kawai, A 2017, 'Efficacy of trabectedin in patients with advanced translocation- related sarcomas: Pooled analysis of two phase II studies', Oncologist, vol. 22, no. 8, pp. 980-988. https://doi.org/10.1634/theoncologist.2016-0064
Takahashi, Mitsuru ; Takahashi, Shunji ; Araki, Nobuhito ; Sugiura, Hideshi ; Ueda, Takafumi ; Yonemoto, Tsukasa ; Morioka, Hideo ; Hiraga, Hiroaki ; Hiruma, Toru ; Kunisada, Toshiyuki ; Matsumine, Akihiko ; Shimura, Masashi ; Kawai, Akira. / Efficacy of trabectedin in patients with advanced translocation- related sarcomas : Pooled analysis of two phase II studies. In: Oncologist. 2017 ; Vol. 22, No. 8. pp. 980-988.
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abstract = "Background. Trabectedin is reported as effective, especially against translocation-related sarcomas (TRSs) after failure of or intolerance to standard chemotherapy. We conducted two phase II studies of TRS, confirming high efficacy of 1.2 mg/m2 trabectedin. The updated data of 66 patients in these studies was integrated to evaluate the efficacy of trabectedin against each histological subtype, and analyze final overall survival (OS). Methods. Trabectedin was administered on day one of a 21-day cycle. Efficacy was assessed using progression-free survival (PFS), OS, and best overall response. An analysis of OS and PFS was performed for subgroups divided by baseline lymphocyte count (<1,000/µL,≥µ1,000/lL) or number of previous chemotherapy regimens (0, 1, 2 ≥3 regimens), and a Weibull parametric model was used to estimate the numerical relationship between lymphocyte count and PFS and OS. Results. Median PFS and OS in overall patients were 5.6 (95{\%} confidence interval [CI]: 4.1-7.3) and 17.5 months (95{\%} CI: 12.6-23.6), respectively. PFS in the myxoid and round-cell liposarcoma (MRCL) group (7.4 months [95{\%} CI: 5.6-11.1]) was longer than in the other subtypes. The response rate was also highest in the MRCL group. Median OS was longer in patients with baseline lymphocyte counts ≥1,000/µL than in those with counts of <1,000/µL, but median PFS was not different between the two subgroups. Conclusion. Our updated and pooled data showed that trabectedin exerted prolonged disease control and antitumor effects in patients with advanced TRS, especially in MRCL.We consider that the subgroup analyses also provide important information for trabectedin treatment in patients with TRS.",
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