Doxorubicin and Olaratumab Versus Doxorubicin, Ifosfamide, and Mesna for Treatment of Advanced Soft Tissue Sarcomas

Doxorubicin and Olaratumab Versus Doxorubicin, Ifosfamide, and Mesna for Treatment of Advanced Soft Tissue Sarcomas:



Objective:

We compared the outcomes in soft tissue sarcoma (STS) treated with olaratumab and doxorubicin (OD) versus doxorubicin, ifosfamide, and mesna (AIM) to assess whether OD could supersede AIM in STS therapy.

Methods:

A single-institution, retrospective study of STS treated for advanced disease with OD or AIM in 2013 to 2017 was conducted. Demographic and clinical parameters were compared by Fisher’s exact test. Kaplan-Meier and Cox analyses examined progression-free survival (PFS) and overall survival (OS). Adverse events were compared.

Results:

Thirty patients (13 OD, 17 AIM) were included. OD was administered more commonly after first-line therapy (54% OD vs. 6% AIM, P=0.0005). The 2 groups did not differ in other parameters. Median OS [OD: 14.2 mo, 95% confidence interval (CI): 7.1-not reached; AIM 19.9 mo, 95% CI 9.5-35.5; hazard ratio: 0.99, 95% CI: 0.38-2.59, P=0.99] and PFS (OD: 2.6 mo, 95% CI: 1.3-7; AIM 6.4 mo, 95% CI: 1.5-14.5; hazard ratio: 0.57, 95% CI: 0.26-1.24, P=0.16) were not statistically different, although median values favored AIM. Grade 3 to 4 neutropenia, but not febrile neutropenia, was more frequent with OD.

Conclusions:

OD and AIM did not differ with respect to either OS or PFS. Although this study’s size initially appeared the most likely explanation, lack of significant activity of olaratumab was subsequently reported in the phase III trial of OD. Our results suggest that future conditional oncology drug approvals should be accompanied by mandated registries to monitor outcomes of patients treated after conditional approval, but before full approval.

Results of this study were presented as a poster at the annual meeting of the Connective Tissue Oncology Society, 8-11 November 2017, Maui, HI.

S.M.P. receives research funding from Merck, EMD Serono, Incyte, Presage, Janssen, Oncosec and Juno. He has received honoraria or has served on advisory boards for Eli Lilly, Seattle Genetics, Bayer, Tempus, Daiichi Sankyo and Blueprint Medicine. M.J.W. receives research funding from Athenex. He has received travel support from GSK and Adaptimmune. He has received honoraria or has served on advisory boards for Adaptimmune and Deciphera. L.D.C. receives research funding from Eli Lilly, AADi, BluePrint Medicine, Iterion, Gradalis, Philogen, Advenchen Laboratories, and CBA Pharma. L.D.C. institution has received funding from Eli Lilly for conduct of clinical trials. L.D.C. has received honoraria or has served on advisory boards for BluePrint Medicines and Regeneron. The other authors declare no conflicts of interest.

Reprints: Lee D. Cranmer, MD, PhD, 825 Eastlake Ave. East, CE2-128, Seattle, WA 98109. Email: lcranmer@seattlecca.org.

Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.