Growth modulation index as metric of clinical benefit assessment among advanced soft tissue sarcoma patients receiving trabectedin as a salvage therapy

Ann Oncol. 2013 Feb;24(2):537-542. doi: 10.1093/annonc/mds470. Epub 2012 Nov 1.

Abstract

Background: The growth modulation index (GMI) is the ratio of time to progression with the nth line (TTP(n)) of therapy to the TTP(n)(-1) with the n-1th line. GMI >1.33 is considered as a sign of activity in phase II trials.

Patients and methods: This retrospective analysis evaluated the concordance between the GMI and the efficacy outcomes in 279 patients with advanced soft tissue sarcoma (ASTS) treated with trabectedin 1.5 mg/m² (24-h infusion every 3 weeks) in four phase II trials.

Results: One hundred and forty-two (51%) patients received one prior line and 137 ≥ 2 lines. The median TTP(n) was 2.8 months (range 0.2-26.8), whereas the median TTP(n)(-1) was 4.0 months (0.3-79.5). The median GMI was 0.6 (0.0-14.4). Overall, 177 patients (63%) had a GMI <1; 21 (8%) a GMI equal to 1-1.33 and 81 (29%) a GMI >1.33, which correlated with the median overall survival in those patients (9.1, 13.9 and 23.8 months, respectively, P = 0.0005). A high concordance rate between the GMI and response rate (P < 0.0001) and progression-free survival (PFS, P < 0.0001) was observed. Good performance status (PS) was the only factor associated with GMI >1.33 (PS = 0; P < 0.04).

Conclusions: A high GMI was associated with favorable efficacy outcomes in patients treated with trabectedin. Further research is needed to assess GMI as an indicator in this setting.

Publication types

  • Clinical Trial, Phase II
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antibiotics, Antineoplastic / therapeutic use
  • Antineoplastic Agents, Alkylating / therapeutic use*
  • Cell Proliferation / drug effects*
  • Dioxoles / therapeutic use*
  • Disease-Free Survival
  • Doxorubicin / therapeutic use
  • Female
  • Humans
  • Male
  • Middle Aged
  • Retrospective Studies
  • Salvage Therapy
  • Sarcoma / drug therapy*
  • Sarcoma / metabolism
  • Sarcoma / mortality
  • Sarcoma / pathology
  • Tetrahydroisoquinolines / therapeutic use*
  • Trabectedin
  • Treatment Outcome
  • Young Adult

Substances

  • Antibiotics, Antineoplastic
  • Antineoplastic Agents, Alkylating
  • Dioxoles
  • Tetrahydroisoquinolines
  • Doxorubicin
  • Trabectedin