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

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.

• Authors: N Penel, G D Demetri, J Y Blay, S Cousin, R G Maki, S P Chawla, I Judson, M von Mehren, P Schöffski, J Verweij, P Casali, S Rodenhuis, H J Schütte, A Cassar, J Gomez, A Nieto, P Zintl, M J Pontes, A Le Cesne
• Journal: Annals of oncology : official journal of the European Society for Medical Oncology (Ann Oncol) Vol. 24 Issue 2 Pg. 537-542 (Feb 2013) ISSN: 1569-8041 [Electronic] England
• PMID: 23117071 (Publication Type: Clinical Trial, Phase II, Journal Article, Randomized Controlled Trial)

Chemical References

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

Topics

• 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, metabolism, mortality, pathology)
• Tetrahydroisoquinolines (therapeutic use)
• Trabectedin
• Treatment Outcome
• Young Adult