Study Finds Adding Olaratumab to Doxorubicin Improves Survival in Advanced Soft-Tissue Sarcoma


Key Points

  • The addition of olaratumab to doxorubicin improved prolonged progression-free in patients with advanced soft-tissue sarcoma.
  • Median overall survival was increased by 11.8 months in the olaratumab group.

The addition of olaratumab, an anti–platelet-derived growth factor receptor alpha (anti–PDGFRα) antibody, to doxorubicin resulted in prolonged progression-free and overall survival in the phase II evaluation of patients with advanced soft-tissue sarcoma, according to findings reported by Tap et al in The Lancet.

Study Details

In the phase II portion of an open-label phase Ib/II trial, 133 patients with advanced or metastatic disease and no previous anthracycline treatment from 16 U.S. sites were randomized between October 2010 and January 2013 to receive olaratumab at 15 mg/kg intranveously (IV) on days 1 and 8 plus doxorubicin at 75 mg/m2 (n = 66) or doxorubicin alone (n = 67) on day 1 of each 21-day cycle for up to eight cycles. The phase II primary endpoint was investigator-assessed progression-free survival using a two-sided α level of 0.2 and a statistical power of 0.8.

Patients had a median age of 58 to 59 years, and 83% to 90% were white; more patients in the olaratumab group were women (61% vs 51%). Two patients in each group did not begin study treatment.

Survival Outcomes

Median progression-free survival was 6.6 months (95% confidence interval [CI] = 4.1–8.3 months) in the olaratumab group vs 4.1 months (95% CI = 2.8–5.4 months) in the control group (stratified hazard ratio [HR] = 0.67, P = .0615, meeting the protocol-defined significance level for final progression-free survival). On blinded independent retrospective review, the hazard ratio was 0.67 (P = .1208), with median progression-free survival of 8.2 vs 4.4 months.

Median overall survival was 26.5 months (95% CI = 20.9–31.7 months) vs 14.7 months (95% CI = 9.2–17.1 months; stratified HR = 0.46, P = .0003). Benefit of olaratumab was consistent across subgroup stratification factors, including histologic tumor type, number of lines of previous treatment, and PDGFRα expression status. The objective response rate was 18.2% vs 11.9% (= .3421).

Treatment after disease progression was received by more than 65% of patients in each group, including olaratumab in 46% of the doxorubicin group. A sensitivity analysis with censoring at the time of starting any new anticancer treatment yielded a similar hazard ratio of 0.425 (P = .0284).

Adverse Events

Adverse events of any grade that were more common in the olaratumab group included neutropenia (58% vs 35%; grade ≥ 3 in 53% vs 33%), mucositis (53% vs 35%), nausea (73% vs 52%), vomiting (45% vs18%), and diarrhea (34% vs 23%). Febrile neutropenia of grade ≥ 3 occurred in 13% vs 14%.

The investigators concluded: “This study of olaratumab with doxorubicin in patients with advanced soft-tissue sarcoma met its predefined primary endpoint for progression-free survival and achieved a highly significant improvement of 11.8 months in median overall survival, suggesting a potential shift in the treatment of soft-tissue sarcoma.”

The study was funded by Eli Lilly and Company.

William D. Tap, MD, of Memorial Sloan Kettering Cancer Center, is the corresponding author of The Lancet article.

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