Correlation between a new growth modulation index (GMI)-based Geistra score and efficacy outcomes in patients (PTS) with advanced soft tissue sarcomas (ASTS) treated with trabectedin (T): A Spanish group for research on sarcomas (GEIS-38 study).

Abstract

11070 Background: The GMI is a marker of drug activity and represents an intra-patient comparison of successive time to progression (TTP), defined as the TTP ratio between the second (or later) line (TTPn) of therapy divided by the prior line (TTPn−1). Defining a clinical profile of pts with GMI >1.33 could help to identify pts who can gain greater benefit from T. Methods: We retrospectively evaluated the concordance between the GMI and the efficacy outcomes and clinical profiles of 198 pts with ASTS treated with trabectedin 1.5 mg/m² (24-h infusion q3w) as a 2nd or further-line treatment from Jan 2007 to Jun 2016. Results: After a median follow-up of 58 months (m; range: 18-172) median overall survival from ASTS diagnosis (MOS) and from T (MT-OS) were 27.5 m (23-32.1) and 10.8 m (8.9-12.7), respectively, while median TTP from T (MT-TTP) and T-1 were 3.4 m (2.8-4) and 3.5 m (2.8-4.2). Overall, 106 pts (53%) had a GMI <1; 22 (11%) a GMI=1-1.33 and 70 pts (35%) a GMI >1.33. A high GMI (<1.33 vs >1.33) correlated with favorable efficacy outcomes: MT-OS: 23 vs 36 m (p<0.001), MT-TTP 2.3 vs 8.2 m (p<0.001) and clinical benefit (objective response + stable disease) 23% vs 68% (p=0.001). The multivariate analysis identified L-type sarcoma (Odds ratio: 1.99, 95% CI 1.06-3.71), metastatic free interval (MFI) from initial diagnosis > 8.1 m (2.24, 95%CI 1.19-4.18) and Karnofsky >80 (2.3, 95%CI 1.00-5.28) as factors independently associated to GMI> 1.33. Based on these 3 variables we defined a new GEISTRA score assigning 1 point for each adversely affected variable: non L-Sarcoma, MFI<8.1m or Karnofsky <80. This score showed a strong correlation with MT-TTP (p<0.001) and MT-OS (p<0.001). Conclusions: Based on the high GMI we defined a new GEISTRA score, which is strongly associated with favorable efficacy outcomes in pts with ASTS treated with T. Thus, GEISTRA score could be a potentially useful predictable clinical tool for T benefit. [Table: see text]

A Growth Modulation Index-Based GEISTRA Score as a New Prognostic Tool for Trabectedin Efficacy in Patients with Advanced Soft Tissue Sarcomas: A Spanish Group for Sarcoma Research (GEIS) Retrospective Study

“…With this in mind, a new GMI-based score, GEISTRA, which showed a strong correlation with clinical efficacy endpoints (ORR, TTP and OS) was defined. We previously defined this score in a training cohort, and validated with an additional validation cohort [ 16 ]. Specifically, the independent worse prognostic variables comprising the GEISTRA score were MFI < 5 months, Karnofsky < 80%, Non L-sarcomas and obtaining clinical benefit rate in the previous systemic line.…”

“…To develop the new score, the series was split into training and validation cohorts. The training set was the original one which the model was stemmed from l [ 16 ]. The optimal cutoff of the quantitative variable metastatic-free interval (MFI) was calculated through Receiver Operating Curves (ROC).…”

“…Based on the results of a preliminary analysis of data from 198 patients with ASTS treated with trabectedin (training cohort), we previously defined a new GEISTRA score, identifying L-sarcomas, metastatic-free interval (MFI) from initial diagnosis and Karnofsky performance status (KS) as independently associated prognostic variables associated with high GMI of >1.33 [ 16 ]. In this retrospective study, we have further analyzed data from 191 other patients considered as the validation cohort (total population: n = 357), with the aim of validating the GEISTRA score and additionally characterizing a clinical profile of the patients that may benefit most from trabectedin.…”

Clinical characteristics of sarcoma cases in which long-term disease control was achieved with trabectedin treatment: A retrospective study

“…Available data were also collected for patients who had undergone next-generation sequencing (NGS) analysis or microsatellite instability (MSI) testing using resected/biopsied tumor tissues. The GEISTRA score proposed by the Spanish sarcoma research group is an index associated with prognosis in trabectedin-treated patients [ 9 ]. This score was calculated using three indices (non-L-sarcoma, metastatic-free interval from initial diagnosis <8.1 months, and Karnofsky PS <80).…”