@article{4c5cfecca246471783badd554dc82ee2,
title = "Efficacy and tolerability of trabectedin in elderly patients with sarcoma: Subgroup analysis from a phase III, randomized controlled study of trabectedin or dacarbazine in patients with advanced liposarcoma or leiomyosarcoma",
abstract = "Background Treatment options for soft tissue sarcoma (STS) patients aged ≥65 years (elderly) can be limited by concerns regarding the increased risk of toxicity associated with standard systemic therapies. Trabectedin has demonstrated improved disease control in a phase III trial (ET743-SAR-3007) of patients with advanced liposarcoma or leiomyosarcoma after failure of anthracycline-based chemotherapy. Since previous retrospective analyses have suggested that trabectedin has similar safety and efficacy outcomes regardless of patient age, we carried out a subgroup analysis of the safety and efficacy observed in elderly patients enrolled in this trial. Patients and methods Patients were randomized 2: 1 to trabectedin (n = 384) or dacarbazine (n = 193) administered intravenously every-3-weeks. The primary end point was overall survival (OS); secondary end points were progression-free survival (PFS), time-to-progression, objective response rate (ORR), duration of response, symptom severity, and safety. A post hoc analysis was conducted in the elderly patient subgroup. Results Among 131 (trabectedin = 94; dacarbazine = 37) elderly patients, disease characteristics were well-balanced and consistent with those of the total study population. Treatment exposure was longer in patients treated with trabectedin versus dacarbazine (median four versus two cycles, respectively), with a significantly higher proportion receiving prolonged therapy (≥6 cycles) in the trabectedin arm (43% versus 23%, respectively; P = 0.04). Elderly patients treated with trabectedin showed significantly improved PFS [4.9 versus 1.5 months, respectively; hazard ratio (HR)=0.40; P = 0.0002] but no statistically significant improvement in OS (15.1 versus 8.0 months, respectively; HR = 0.72; P = 0.18) or ORR (9% versus 3%, respectively; P = 0.43). The safety profile for elderly trabectedin-treated patients was comparable to that of the overall trabectedin-treated study population. Conclusions This subgroup analysis of the elderly population of ET743-SAR-3007 suggests that elderly patients with STS and good performance status can expect clinical benefit from trabectedin similar to that observed in younger patients. Trial registration www.clinicaltrials.gov, NCT01343277.",
keywords = "elderly, soft tissue sarcomas, trabectedin",
author = "Jones, {R. L.} and Demetri, {G. D.} and Schuetze, {S. M.} and M. Milhem and A. Elias and {Van Tine}, {B. A.} and J. Hamm and S. McCarthy and G. Wang and T. Parekh and R. Knoblauch and Hensley, {M. L.} and Maki, {R. G.} and S. Patel and {Von Mehren}, M.",
note = "Funding Information: This work was supported by Janssen Research & Development, LLC (grant number P30 CA006927). Funding Information: RLJ has been a consultant for Janssen Oncology and PharmaMar. GD has received research support from Bayer, Pfizer, Novartis, and Janssen Oncology to Dana-Farber for his role as PI in clinical trial agreements in the Dana-Farber Cancer Institute sarcoma unit and has received consulting fees from Novartis, Pfizer, EMD-Serono, Sanofi Oncology, Janssen Oncology, PharmaMar, Daiichi-Sankyo, Adaptimmune, Eisai, and Epizyme. GD also reports a patent licensed to Novartis from Dana-Farber with royalty paid to Dana-Farber; membership on the Board of Directors for Blueprint Medicines; and scientific advisory board membership as well as consulting fees and minor equity for Blueprint Medicines, GI Therapeutics, and Caris Life Sciences. SMS served as a paid consultant to Janssen Oncology and received research funding from Janssen Oncology, Lilly, Plexicon, Daiichi Sankyo, AB Science, and Amgen. MM has served on advisory boards for Eisai, BMS, Genentech, Novartis, and EMD-Serono. AE reports having stocks <$10 000 for Johnson & Johnson, Merck, Lilly, Gilead, Pfizer, and Abbvie. BVT has served as an advisor and speaker for and paid consultant to Johnson & Johnson. John Hamm serves on a speakers{\textquoteright} board for Janssen and has received research funding from Janssen. SM, GW, TP, and RK are employees of Janssen and own stock in Johnson & Johnson. MH has been paid for consulting/advisory roles for Lilly, EMD Serono, and Janssen Oncology and has received research funding from Janssen Oncology. Additionally, MH is supported in part by the MSK Cancer Center Support Grant P30 CA008748. RM has received consulting fees (personal) and research support (institution) from Janssen and PharmaMar. SP has received grants from Janssen, Eisai, and Morphotek and has been a consultant for Janssen, Eisai, Morphotek, Bayer, EMD-Serono, Eli Lilly, Bayer, Epizyme, and Novartis. MvM served on the scientific leadership committee of the ET743-SAR-3007 study and has served as a paid consultant to Esai, CytRx, and Janssen. Funding Information: This study was supported by Janssen Research & Development, LLC. In addition to those who participated as authors, we thank all site investigators for their involvements in the ET743-SAR-3007 study as well as the patients who participated. The authors also thank Gianna Paone, MS, of Janssen Scientific Affairs, LLC, for providing medical writing, editorial, and submission support. Publisher Copyright: {\textcopyright} 2018 The Author(s).",
year = "2018",
month = sep,
day = "1",
doi = "10.1093/annonc/mdy253",
language = "English",
volume = "29",
pages = "1995--2002",
journal = "Annals of Oncology",
issn = "0923-7534",
number = "9",
}