Ridaforolimus as a single agent in advanced endometrial cancer: results of a single-arm, phase 2 trial

Abstract

Background: This open-label, multicentre, phase 2 trial evaluated the efficacy and tolerability of the mammalian target of rapamycin inhibitor ridaforolimus in women with advanced endometrial cancer.

Methods: Women with measurable recurrent or persistent endometrial cancer and documented disease progression were treated with ridaforolimus 12.5 mg intravenously once daily for 5 consecutive days every 2 weeks in a 4-week cycle. The primary end point was clinical benefit response, defined as an objective response or prolonged stable disease of 16 weeks or more.

Results: In all, 45 patients were treated with single-agent ridaforolimus. Clinical benefit was achieved by 13 patients (29%), including 5 (11%) with confirmed partial responses and 8 (18%) with prolonged stable disease. All patients with clinical benefit response received ridaforolimus for more than 4 months. In this heavily pretreated population, the 6-month progression-free survival was 18%. Ridaforolimus was generally well tolerated: adverse events were predictable and manageable, consistent with prior studies in other malignancies. Overall, the most common adverse events were diarrhoea (58%) and mouth sores (56%); most common grade 3 or higher adverse events were anaemia (27%) and hyperglycaemia (11%).

Conclusion: Single-agent ridaforolimus has antitumor activity and acceptable tolerability in advanced endometrial cancer patients. Further clinical evaluation of ridaforolimus is warranted.

Figure 1

Time on trial with ridaforolimus.

Figure 2

Patient aged 59 years with papillary serous endometrial cancer with multiple metastases treated with ridaforolimus. Baseline scan revealed a 25 × 23 mm mass in the right lung, which decreased to 14 × 13 mm after cycle 2 of therapy, and by cycle 4 was confirmed as a PR by RECIST guidelines.

Figure 3

Waterfall plot showing distribution of the best percentage change in target lesion size from baseline for an individual patient (n=35; not evaluable, n=10). The lines (–30 and +20%) indicate the region with change from baseline that typically represent SD based on RECIST guidelines.