Rigosertib, an inhibitor of PI3K and PLK signaling pathways, did not significantly improve overall survival compared with best supportive care in patients with myelodysplastic syndromes with excess blasts following failure of a hypomethylating drug, a study published in the journal The Lancet Oncology has shown.1

Although hypomethylating drugs like azacitidine and decitabine are the standard treatment for patients with high-risk myelodysplastic syndromes, survival is poor after failure of these agents and there is no approved second-line therapy.

Therefore, researchers sought to compare the efficacy of rigosertib plus best supportive care with that of best supportive care alone in patients with myelodysplastic syndromes with excess blasts after treatment failure with azacitadine or decitabine.

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For the phase 3 study, researchers enrolled 299 patients with refractory anemia with excess blasts (RAEB)-1, RAEB-2, RAEB-t, or chronic myelomonocytic leukemia, and treatment failure with a hypomethylating drug in the past 2 years. Patients were randomly assigned 2:1 to receive rigosertib 1800 mg per day via a 72-hour continuous intravenous infusion every other week or best supportive care with or without low-dose cytarabine.

Results showed that at a median follow-up of 19.5 months, median overall survival was 8.2 months (95% CI, 6.1 – 10.1) with rigosertib compared with 5.9 months (95% CI, 4.1 – 9.3) with best supportive care (HR, 0.87; 95% CI, 0.67 – 1.14; P = .33).

In terms of safety, the most common grade 3 or higher adverse events in the rigosertib group were anemia, thrombocytopenia, neutropenia, febrile neutropenia, and pneumonia. Forty-one of the 184 patients in the rigosertib arm died due to adverse events and 3 deaths were due to rigosertib therapy.

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Although rigosertib failed to improve survival in this patient population, a phase 3 trial is underway to evaluate rigosertib in specific subgroups of patients deemed to be at high risk, including those with very high risk per the Revised International Prognostic Scoring System criteria.


  1. Garcia-Manero G, Fenaux P, Al-Kali A, et al. Rigosertib versus best supportive care for patients with high-risk myelodysplastic syndromes after failure of hypomethylating drugs (ONTIME): a randomised, controlled, phase 3 trial [published online ahead of print March 8, 2016]. Lancet Oncol. doi: 10.1016/S1470-2045(16)00009-7.