A phase II trial of thalidomide in patients with refractory uterine carcinosarcoma and correlation with biomarkers of angiogenesis: A Gynecologic Oncology Group study

ObjectivesTo evaluate the efficacy and adverse events of thalidomide in previously-treated, measurable, persistent or recurrent carcinosarcoma of the uterus, and to explore associations between angiogenic markers with patient demographics and clinical outcome.MethodsEligible, consenting patients were treated until disease progression or toxicity intervened with daily starting dose of 200 mg thalidomide/day that was increased by 200 mg every 2 weeks to a target dose of 1000 mg/day. Endpoints included progression-free survival (PFS) ≥ 6 months (primary), toxicity, response, overall PFS and survival. Pre- and post-treatment plasma were evaluated for a panel of angiogenic biomarkers and assessed against clinical outcomes.ResultsOf 55 enrolled patients, 45 were evaluable for toxicity and survival. Two patients (4%; 90% CI 1–13%) experienced a partial response, and 8 (18%; 90% CI 9–30%) had PFS ≥ 6 months. Median PFS was 1.9 months and median survival was 5.9 months. Grade 2–3 sensory neuropathy was noted in 6 patients, and 4, 3, and 3 patients experienced grade 3 sedation, fatigue, and constipation, respectively. Three patients had grade 4 adverse events (2 thromboembolic, 1 anemia). High pre-treatment VEGFA levels were associated with poorer PFS and survival.ConclusionsTreatment with thalidomide met the protocol specified goal of prolonging PFS at 6 months. However, based on results with newer agents, the activity was insufficient to support further investigation. Association between pre-treatment VEGFA and prognosis in this population supports further evaluation of anti-angiogenic therapies in uterine carcinosarcoma.

► Thalidomide produced low RR.
► Prolonged PFS > 6 months was observed in 18% of women with chemo-refractory uterine CS.
► Higher pre-treatment VEGFA levels were associated with poorer PFS and survival.