No OS Benefit in Adding Olaratumab to Doxorubicin for Advanced STS

Adding olaratumab to doxorubicin therapy in patients with advanced soft tissue sarcoma (STS) did not lead to any significant improvements in overall survival (OS), according to findings from a study by William D. Tap, MD, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, and colleagues (JAMA. 2020;323[13]:1266-1276).

Patients with advanced STS have a median OS <2 years, and a phase 2 study of this patient population demonstrated an OS benefit with the addition of olaratumab to doxorubicin versus doxorubicin alone, Dr Tap et al explained.

Thus, they sought to determine the efficacy of doxorubicin plus olaratumab in anthracycline-naive adults with unresectable locally advanced or metastatic STS in the confirmatory, phase 3, double-blind ANNOUNCE trial.

A total of 509 patients (mean age, 56.9 years) were included in the study, which was conducted at 110 sites across 25 countries between September 2015 and December 2018.

The final date of follow-up was December 5, 2018, and all patients had a median follow-up of 31 months.

These patients were randomized in a 1:1 ratio to receive doxorubicin 75 mg/m² plus olaratumab 20 mg/kg in cycle 1 and 15 mg/kg in subsequent cycles (n = 258) or doxorubicin 75 mg/m² plus placebo on days 1 and 8 (n = 251) for up to 8 cycles (each spanning 21 days), followed by monotherapy with olaratumab or placebo.

The primary end points of the ANNOUNCE study were OS rates with either regimen in the overall population and in patients with leiomyosarcoma (LMS; 46%).

Ultimately, Dr Tap and colleagues ovserved no statistically significant difference in OS between the doxorubicin plus olaratumab and doxorubicin plus placebo arms in either population (overall: hazard ratio [HR], 1.05; 95% CI, 0.84-1.30; P = .69, median OS, 20.4 months vs 19.7 months; LMS: HR, 0.95; 95% CI, 0.69-1.31; P = .76, median OS, 21.6 months vs 21.9 months).

Among all patients in the study, the most common (≥15%) adverse events grade ≥3 were neutropenia, leukopenia, and febrile neutropenia.

“In this phase 3 clinical trial of patients with advanced STS, treatment with doxorubicin plus olaratumab vs doxorubicin plus placebo resulted in no significant difference in [OS]. The findings did not confirm the [OS] benefit observed in the phase 2 trial,” Dr Tap and colleagues concluded.—Hina M. Porcelli