Subgroup analysis of older patients treated within the randomized phase 3 doxorubicin versus doxorubicin plus evofosfamide (SARC021) trial

J Geriatr Oncol. 2020 Apr;11(3):463-469. doi: 10.1016/j.jgo.2019.05.008. Epub 2019 May 22.

Abstract

Background: More than half of patients with soft tissue sarcoma (STS) are aged ≥65 years (older), however contemporary data on the efficacy/safety of anthracycline chemotherapy in older patients with STS are lacking.

Methods: SARC021 randomized patients to receive first-line doxorubicin or doxorubicin plus evofosfamide. The main aim of this study was to compare the outcome and safety of first-line anthracycline-based therapy in older patients compared with those <65 years. IRB approval was obtained at all participating sites and this research meets requirements for protection of human subjects.

Results: Of 640 patients, 209 (33%) were older, with a median age 70 (range 65-89) years. The median overall survival (OS) was 16.7 months (95%CI: 13.2-20.0) in older patients compared to 20.1 months (95%CI: 16.9-23.2) in those aged <65 years (n = 431), HR 1.21 (95%CI: 0.99-1.48), p = .057. The median progression-free survival (PFS) in older patients was 6.3 months (95%CI: 5.8-7.2) compared to 6.0 (95%CI: 5.1-6.4) in those <65 years, HR 0.86 (95%CI: 0.70-1.05), p = .14. Older patients had significantly more hematological (141 [67%] versus 208 [48%], p < .0001), non-hematological (131 [63%] versus 215 [50%], p = .0097) and ≥ Grade 3 adverse events (178 [85%] versus 299 [69%], p = .0002), compared to younger patients. More older patients (30, 14%) stopped treatment due to adverse events compared to younger patients (22, 5%), p = .0001.

Conclusions: The efficacy of first-line anthracycline-based chemotherapy did not differ significantly between older and younger advanced sarcoma patients. Significantly more older patients stopped chemotherapy due to adverse events. These results provide a benchmark for daily clinical practice and future trials in older patients.

Keywords: Anthracycline; Chemotherapy; Efficacy; First-line; Older; Soft tissue sarcomas; Toxicity.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Antibiotics, Antineoplastic / therapeutic use*
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Doxorubicin / therapeutic use*
  • Humans
  • Nitroimidazoles / pharmacology*
  • Phosphoramide Mustards / pharmacology*

Substances

  • Antibiotics, Antineoplastic
  • Nitroimidazoles
  • Phosphoramide Mustards
  • TH 302
  • Doxorubicin