Outcomes of patients (pts) with advanced soft-tissue sarcomas (STS) treated in clinical trials (CTs) versus expanded access programs (EAPs): A decade of experience with single-agent trabectedin (Tr).
Authors: G. D. Demetri, J. Blay, P. Schoffski, R. G. Maki, A. J. Yovine, I. R. Judson, P. G. Casali, J. Gomez, E. Bayever, A. Le Cesne
Journal: Journal of Clinical Oncology (2010)

10029 Background: Pts who do not qualify for CTs may enter EAPs when available, allowing treatment with new agents prior to regulatory approval when no other options are left. Extensive data collected with single-agent Tr for more than a decade allow us to compare outcomes from this unselected population with pts rigorously selected for CTs. Methods: Data on 879 STS pts included in CTs and EAPs globally were retrospectively analyzed. 620 pts were included in phase II CTs (1999-2008) and 259 were in EAPs (1998-2002). Several Tr dose and schedule regimens were used. Results: See Table. Conclusions: Data with Tr offer a powerful opportunity to compare CT data with clinical practice in EAPs. As expected, the EAP pts had a worse ECOG PS, a wider variety of rare subtypes, increased likelihood of bone and brain metastases and were more heavily pretreated. Nonetheless, clinical activity was noted in both CT and EAP groups. EAPs are potentially useful for patient care as well as for evaluating the comparative effectiveness of new agents that can be expected in clinical practice following regulatory approval. CT (n=620) EAP (n=259) Median age (range) 52(14-81) 47(14-80) Schedule (%) 56/23/21% 70/30/0% 1.5 mg/m2 q3wk 24-h/1.3 mg/m2 q3wk 3-h/0.58 mg/m2 qwk 3- h ECOG PS 0-1/2-4 99%/1% 80%/18% Histology (most common)(%) 49/24/7/3/2/2/12 26/17/13/8/7/5/25 Leiomyosarcoma/liposarcoma/synovial sarcoma/malignant fibrous histiocytoma/fibrosarcoma/rhabdomyosarcoma/others Histology grade 1-2 / 3-4 30%/50% 27%/41% Metastasis (most common)(%) 65/25/7/- 64/22/19/2 Lung/liver/bone/brain No prior chemotherapy (ChT)(%) 81/14 57/43 1-2/≥3 Prior surgery 96% 93% Prior radiotherapy 52% 55% Prior ChT (%) 95% 100% Agent 78/14/11/7/2 92/6/2/10/- Anthracycline+Ifosfamide/anthracycline/gemcitabine+docetaxel/gemcitabine/ifosfamide Prior chemo setting (%) 68/8/19 79/4/17 Advanced/adjuvant/both Response rate with Tr (%) CR/PR/SD * 1/6/42 0/5/32 Tr median cycles (range) 3 (1-59) 2 (1-22) Median PFS, months (95% CI) 2.3 (2.0-2.8) 1.6 (1.5-2.0) Median OS, months (95% CI) 13.0(11.7-14.3) 9.1(6.5-11.2) * Median of 6/4 Tr cycles received in CT/EAP pts. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Johnson & Johnson, PharmaMar Amgen, ARIAD, ArQule, Daiichi Sankyo, Genentech, GlaxoSmithKline, Infinity, Johnson & Johnson, Novartis, Pfizer, PharmaMar, Roche, sanofi-aventis, ZIOPHARM Oncology Johnson & Johnson, PharmaMar, zeltia GlaxoSmithKline, Novartis, Pfizer, PharmaMar, Roche Amgen, ARIAD, ArQule, Daiichi Sankyo, Genentech, GlaxoSmithKline, Infinity, Johnson & Johnson, Lilly, Novartis, Pfizer, PharmaMar, Roche, sanofi-aventis, Schering-Plough, ZIOPHARM Oncology ARIAD, ArQule, Daiichi Sankyo, Infinity, Johnson & Johnson, PharmaMar Novartis, PharmaMar