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.

The aim of this study was to identify an easily reliable prognostic score that selects the subset of advanced soft tissue sarcoma (ASTS) patients with a higher benefit with trabectedin in terms of time to progression and overall survival. A retrospective series of 357 patients with ASTS treated with trabectedin as second- or further-line in 19 centers across Spain was analyzed. First, it was confirmed that patients with high growth modulation index (GMI > 1.33) were associated with the better clinical outcome. Univariate and multivariate analyses were performed to identify factors associated with a GMI > 1.33. Thus, GEISTRA score was based on metastasis free-interval (MFI ≤ 9.7 months), Karnofsky < 80%, Non L-sarcomas and better response in the previous systemic line. The median GMI was 0.82 (0-69), with 198 patients (55%) with a GMI < 1, 41 (11.5%) with a GMI 1-1.33 and 118 (33.1%) with a GMI > 1.33. The lowest GEISTRA score showed a median of time-to-progression (TTP) and overall survival (OS) of 5.7 and 19.5 months, respectively, whereas it was 1.8 and 3.1 months for TTP and OS, respectively, for the GEISTRA 4 score. This prognostic tool can contribute to better selecting candidates for trabectedin treatment in ASTS.

Real-world evidence of the efficacy and tolerability of trabectedin in patients with advanced soft-tissue sarcoma.

INTRODUCTION: The efficacy and tolerability of trabectedin in patients with soft tissue sarcoma (STS) have been confirmed by various clinical studies involving lipo- and leiomyosarcomas as well as many other subtypes including translocation-related sarcomas. These data have been obtained from randomized phase II and III clinical trials. Studies in real-world clinical practice are necessary to bridge the efficacy-effectiveness gap and complete the body of evidence. Furthermore, reinforcing clinical experience with data from routine clinical practice allows drug management to be optimized and clinical benefits to be maximized. AREAS COVERED: The present review provides the most significant data on the efficacy of trabectedin in real-world studies, and the interpretation of real-world experience with trabectedin, in patients with advanced STS. EXPERT OPINION: Trabectedin has demonstrated durable disease control and an adequate safety profile, indicating it to be a suitable long-term treatment drug associated with a good quality of life. Personalized strategies and individualized objectives are the way forward in the management of STS.

A randomized phase II study of raltitrexed and gefitinib versus raltitrexed alone as second line chemotherapy in patients with colorectal cancer. (1839IL/0143).

PURPOSE: To determine the efficacy of the addition of gefitinib to raltitrexed in patients with colorectal cancer (CRC) that have progressed after first line chemotherapy. The study also sought to explore the safety of the combination and to investigate biomarkers predictive outcome. METHODS: A total of 76 patients were randomized to raltitrexed (3 mg/m(2) i.v.) every 21 days plus either daily gefitinib (250 mg p.o.) or placebo. The primary endpoint of the study was progression free survival (PFS). Tumor tissues were collected to determine the expression of EGFR, pEGFR, pMAPK, and pAkt. RESULTS: Both groups were well balanced with regard to prognostic factors. Treatment was well tolerated with no increased in toxicity except diarrhea and skin rash in the combination group. There were no differences in PFS between the combination arm [63 days (95% CI: 57-84)] compared to the raltitrexed alone arm [72 days (95% CI: 59-132)], or overall survival 361 days (95% CI: 283-533 days) versus 291 days (95% CI: 255-539 days) respectively. The objective response rate was 7.9% (3 patients) (CI 95%: 1,66-21,38) versus 5.3% (2 patients) (CI 0,64-17,75), respectively. The biomarker studies were not conclusive. CONCLUSION: The combination of raltitrexed and gefitinib was well tolerated although was not associated with improved progression free survival in patients with refractory CRC.