Phase II Trial Shows Activity of mTOR Inhibitor Ridaforolimus in Advanced Endometrial Carcinoma


Key Points

  • Ridaforolimus significantly improved progression-free survival in patients with advanced endometrial carcinoma.
  • Treatment discontinuation due to adverse events was more common with ridaforolimus than other agents.

In a randomized phase II trial reported in the Journal of Clinical Oncology, Oza et al found that the mTOR inhibitor ridaforolimus was active in previously treated advanced endometrial carcinoma.

Study Details

In the open-label study, 130 patients with progressive disease after one or two lines of chemotherapy and no hormonal therapy were randomly assigned to receive oral ridaforolimus 40 mg/d for 5 consecutive days followed by 2 days off each week (n = 64) or progestin or the investigator’s choice of chemotherapy (comparator group, n = 66; 42 received progestin). The primary endpoint was progression-free survival on independent radiologic review. Patients had a median age of 66 years, and 95% had received one prior chemotherapy regimen.

Progression-Free Survival

At interim analysis, median progression-free survival was 3.6 months (95% confidence interval [CI] = 2.7–7.3 months) in the ridaforolimus group vs 1.9 months (95% CI = 1.9–2.3 months) in the comparator group (hazard ratio = 0.53, P = .008). Progression-free survival rates were 48% vs 18% at 16 weeks and 38% vs 15% at 24 weeks. The objective response rate was 0% vs 4% (P = .925), and the stable disease rate was 35% vs 17% (P = .021).

Adverse Events

The most common adverse events of any grade in the ridaforolimus group were diarrhea (48%), mucosal inflammation (41%), anorexia (37%), and asthenia (30%). The most common grade ≥ 3 adverse events in the ridaforolimus group were hyperglycemia (19%), anemia (13%), and diarrhea (11%). Treatment was discontinued due to adverse events in 33% of the ridaforolimus group vs 6% of the comparator group.

The investigators concluded: “Oral ridaforolimus shows encouraging activity in advanced endometrial cancer but is associated with significant toxicity. Inhibition of the PI3K/Akt/mTOR pathway may be a viable therapeutic target.”

Amit M. Oza, MD, of Princess Margaret Cancer Centre, is the corresponding author of the Journal of Clinical Oncology article.

The study was supported by Merck. For full disclosures of the study authors, visit

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