Safety and efficacy of trabectedin when administered in the inpatient versus outpatient setting: Clinical considerations for outpatient administration of trabectedin

Abstract

Background: The results of the randomized, phase 3 ET743-SAR-3007 trial demonstrated that trabectedin had a significantly longer progression-free survival (PFS) compared with dacarbazine in patients with advanced leiomyosarcoma/liposarcoma after the failure of prior chemotherapy. Patients randomized to trabectedin received a 24-hour intravenous infusion either in an inpatient or outpatient setting. Herein, the authors reported the safety, efficacy, and patient-reported outcomes based on first infusion site of care.

Methods: Patients were randomized 2:1 to trabectedin (at a dose of 1.5 mg/m2 ) or dacarbazine (1 g/m2 over 20-120 minutes) with overall survival (OS) as the primary endpoint and PFS, time to disease progression, objective response rate, duration of response, safety, and patient-reported symptom scoring as secondary endpoints. The setting of the trabectedin infusion was based on institutional preference and categorized based on the setting of the first infusion.

Results: Of the 378 patients who were treated with trabectedin, 100 (27%) and 277 (73%), respectively, first received trabectedin in the inpatient and outpatient setting. No differences were observed with regard to PFS or OS based on site of care. The median PFS was 4.1 months versus 4.2 months (hazard ratio, 0.90; P = .49) for inpatients versus outpatients, respectively, and the median OS was 14.3 months versus 13.7 months (hazard ratio, 0.89; P = .40), respectively. Grade 3/4 adverse events (classified according to the National Cancer Institute Common Terminology Criteria for Adverse Events [version 4.0]) were reported in 87 inpatients (87%) compared with 219 outpatients (79%); grade 3/4 serious adverse events were reported in 43 inpatients (43%) and 92 outpatients (33%). Extravasation occurred in 0 inpatients and 5 outpatients (2%), whereas the incidence of catheter-related complications was similar between groups (16% vs 15%).

Conclusions: Although the majority of patients who were randomized to trabectedin received outpatient therapy, the outcomes of the current study suggested equivalent safety and efficacy in either setting.

Keywords: extravasation; inpatients; leiomyosarcoma; liposarcoma; outpatients; soft-tissue sarcoma; trabectedin.

Conflict of interest statement

Robin L. Jones has received honoraria and consulting fees from Johnson and Johnson for work performed as part of the current study and has received honoraria and consulting fees from Adaptimmune, Blueprint Medicines, Clinigen, Eisai, Epizyme, Daiichi‐Sankyo, Deciphera Pharmaceuticals Inc, Immune Design, Janssen Oncology, Lilly, Merck, Pfizer, PharmaMar, Tracon, and UpToDate for work performed outside of the current study. Robert G. Maki has received grants from PharmaMar and Janssen to his institution for work performed as part of the current study and the conduct of studies using trabectedin and has acted as a paid member of the Data Safety Monitoring Board for Aadi Bioscience, Deciphera Pharmaceuticals Inc, and Karyopharm; acted as a paid consultant for Arcus, Eisai, and Foundation Medicine; acted as paid consultant for and received travel fees from Bayer; has received a grant from Morphotek; has received a grant from and acted as a paid consultant for GlaxoSmithKline; has received a grant to his institution from and acted as a paid consultant for Janssen/PharmaMar, Lilly, ImClone, Novartis, Pharmacia, Pfizer, Ciba Geigy, Sarcoma Alliance for Research through Collaboration, and Immune Design; has received clinical trials support to his institution from Beta Cat, Daiichi‐Sankyo, Forma Therapeutics, Genentech, Immunocore, Janssen/PharmaMar, Lilly/ImClone, Presage Biosciences, Regeneron, and Tracon Pharmaceuticals; has received honoraria from the American Association for Cancer Research, the American Society of Clinical Oncology, and Medical Oncology Exam Committee membership for American Board of Internal Medicine, and has received royalties from Springer, UpToDate, and Wiley for work performed outside of the current study. Shreyaskumar R. Patel reports grants from Janssen, personal fees from PharmaMar (travel for advisory board), and personal fees from M.J. Hennessey/OncLive (presentation at an educational meeting) for work performed as part of the current study and has acted as a paid consultant for Bayer, Daiichi Sankyo, Eli Lilly, Epizyme, Immune Design, Janssen, and Novartis Oncology; has received grants from Blueprint Medicines; and has received personal fees from CytRx and EMD Serono for work performed outside of the current study. George Wang, Tracy A. McGowan, and Waleed S. Shalaby are employees of Janssen and hold stock in Johnson and Johnson, of which Janssen is a wholly‐owned subsidiary. Roland E. Knoblauch is an employee of Janssen Oncology. Margaret von Mehren received support to the Fox Chase Cancer Center for the conduct of the current study from and has acted as a member of the advisory board and a member of the scientific steering committee for the current study for Janssen, and has acted as a paid consultant and member of the Data and Safety Monitoring Board for Eisai. George D. Demetri has received grants, personal fees, and nonfinancial support (for medical writing) from Janssen and grants, personal fees, and travel support from PharmaMar for work performed as part of the current study; has received grants, personal fees, nonfinancial support, and travel support from Daiichi‐Sankyo, Epizyme, Novartis, and Roche; has received grants, personal fees, and travel support from Adaptimmune, Bayer, Loxo Oncology, and Pfizer; has received personal fees and travel support from EMD Serono, M.J. Hennessey/OncLive, and WIRB‐Copernicus Group; has received personal fees from Sanofi; has received grants and personal fees from Ignyta; has received grants, personal fees, and nonfinancial support from AbbVie; has received personal fees from Mirati Therapeutics, Polaris Pharmaceuticals, and ZioPharm Oncology; has received a grant from GlaxoSmithKline; has received travel support from and holds equity in Blueprint Medicines and equity options in Merrimack Pharmaceuticals; holds equity and equity options in G1 Therapeutics; has received travel support and equity options from Caris Life Sciences; has equity options in Bessor Pharma and Erasca Pharmaceuticals; has received personal fees from and holds equity in Champions Oncology; and has a patent issued and licensed to PharmaMar for trabectedin use for cancer (patent from PharmaMar; no funds from this and no license to the Dana‐Farber Cancer Center or to Dr. Demetri) and a patent issued and licensed to Novartis for imatinib use in gastrointestinal stromal tumor and receives royalties due to patent for work performed outside of the current study.

© 2019 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society.

Figures

Figure 1

Patient disposition of inpatient versus outpatient subgroups of patients who received trabectedin in the ET743‐SAR‐3007 study.