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

Abstract

BACKGROUND\nMore than half of patients with soft tissue sarcoma (STS) are aged ≥65\u202fyears (older), however contemporary data on the efficacy/safety of anthracycline chemotherapy in older patients with STS are lacking.\n\n\nMETHODS\nSARC021 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\u202fyears. IRB approval was obtained at all participating sites and this research meets requirements for protection of human subjects.\n\n\nRESULTS\nOf 640 patients, 209 (33%) were older, with a median age 70 (range 65-89) years. The median overall survival (OS) was 16.7\u202fmonths (95%CI: 13.2-20.0) in older patients compared to 20.1\u202fmonths (95%CI: 16.9-23.2) in those aged <65\u202fyears (n\u202f=\u202f431), HR 1.21 (95%CI: 0.99-1.48), p\u202f=\u202f.057. The median progression-free survival (PFS) in older patients was 6.3\u202fmonths (95%CI: 5.8-7.2) compared to 6.0 (95%CI: 5.1-6.4) in those <65\u202fyears, HR 0.86 (95%CI: 0.70-1.05), p\u202f=\u202f.14. Older patients had significantly more hematological (141 [67%] versus 208 [48%], p\u202f<\u202f.0001), non-hematological (131 [63%] versus 215 [50%], p\u202f=\u202f.0097) and\u202f≥\u202fGrade 3 adverse events (178 [85%] versus 299 [69%], p\u202f=\u202f.0002), compared to younger patients. More older patients (30, 14%) stopped treatment due to adverse events compared to younger patients (22, 5%), p\u202f=\u202f.0001.\n\n\nCONCLUSIONS\nThe 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.