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.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


Advertisement

Advertisement



Advertisement