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Rigosertib-Azacitidine Combo Shows Promise in Patients With MDS, AML
A combination therapy regimen of rigosertib and azacitidine yielded an overall response rate of >50% in patients with myelodysplastic syndromes (MDS), chronic myelomonocytic leukemia (CMML), and acute myeloid leukemia (AML; Leuk Res. 2020;94:106369).
Shyamala C. Navada, MD, Tisch Cancer Institute, Division of Hematology/Oncology, Icahn School of Medicine at Mount Sinai, New York, conducted a phase 1/2 clinical trial of 18 patients, including 9 with MDS, 8 with AML, and 1 with CMML who had never received hypomethylating agents (n = 10) or had relapsed/refractory disease after hypomethylating agent therapy (n = 8).
Patients in the study were given rigosertib, an Ras-effector pathway inhibitor, in 3 successive cohorts (140 mg twice daily, 280 mg twice daily, or 840 mg daily [560 mg morning/280 mg evening]) for 3 weeks of a 4-week cycle and azacitidine 75 mg/m2 daily for 7 days during the second week; the cycle was repeated every 4 weeks.
During a median of 4 cycles, rigosertib plus azacitidine was found to be well-tolerated, with 72% of patients having ≥1 serious adverse events. There were no dose-limiting toxicities observed, and no maximum tolerated dose was established.
Diarrhea (50%), constipation (44%), fatigue (44%), nausea (44%), pneumonia (33%), and back pain (33%) were the most common adverse events.
According to Dr Navada and colleagues, sequential administration of the treatment regimen yielded an overall response rate of 56% in evaluable patients, with responses observed in 7 (78%) patients with MDS/CMML and 2 (29%) patients with AML.
“Further clinical studies are warranted to investigate this doublet therapy in patients with myeloid malignancies,” they concluded.—Hina Porcelli
