Oral decitabine, an oral fixed-dose of combination decitabine and CDA inhibitor cedazuridine, is an FDA-approved therapy for patients with lower-risk myelodysplastic syndromes.
Patients with lower-risk myelodysplastic syndromes (MDS) appeared to benefit from receiving a fixed combination or oral decitabine and cedazuridine (Inqovi), according to results from the phase 3 ASCERTAIN trial. Findings on the combination’s efficacy and tolerability were recently presented during the 2021 American Hematology Society Annual Meeting & Exposition.
“Oral [hypomethylating agents] are a game changer for patients with MDS,” said study author James K. McCloskey, MD. “We’ve known this in high-risk disease, but this brings in an orphan patient population where we haven’t had other options previously. The oral nature of this drug is particularly important to consider when we’re talking about low-risk patients.”
In an interview with Oncology Nursing News®, McCloskey, chief, Leukemia Division, John Theurer Cancer Center, Hackensack Meridian Health, discussed the efficacy of oral decitabine plus cedazuridine, the combination’s potential role in lower-risk MDS, and what this could mean for the patient population.
Oncology Nursing News®: What was the rationale for this study?
McCloskey: Lower-risk MDS are diseases that we typically treat with a focus around a patient’s cytopenias and attempting to improve the quality of life. We understand these patients may live decades with their disease, but symptoms related to anemia and the impact of transfusion burden and iron overload can impact their outcome.
Unfortunately, outside of luspatercept-aamt [Reblozyl] for ring sideroblastic disease or lenalidomide for patients with 5q-minus associated MDS, we don’t have disease-modifying therapies that are helpful in low-risk disease. By contrast, the hypomethylating agents, including decitabine and azacitidine, are standard in higher-risk MDS where we know they improve overall survival, reduce transfusion requirements, and improve quality of life. [On] occasion, we might use these in low-risk patients, but we have not demonstrated that we improve their overall outcomes with the use of hypomethylating agents in low-risk MDS.
That brings us up to oral decitabine, which is an oral fixed dose of combination decitabine and a CDA inhibitor known as cedazuridine. This was FDA approved based on data from the ASCERTAIN trial, a randomized, crossover study that confirmed equivalent exposure to decitabine when we use this the oral fixed-dose combination compared with parenteral azacytidine. What we’re presenting ASH is an exploration of the patients on the ASCERTAIN trial who had lower-risk disease.
What were the methods that were utilized in the follow-up of this study?
The ASCERTAIN trial was a randomized, crossover study, where patients received 1 cycle of parenteral azacitidine. Then, during the remaining cycles of treatment, they were treated with oral combination therapy.
We obtained PK/PD data to confirm that there was equivalent exposure with the oral and parenteral forms. In this abstract, we're looking at those patients treated on the ASCERTAIN study who had low-risk disease.
Could you share the results that were presented at the meeting?
There were 133 patients in total treated on ASCERTAIN, and 69 patients had lower-risk MDS. The vast majority of those had an intermediate 1 disease, so 93% of these patients. When we look at their treatment, the median number of cycles was 9 but there were patients who received up to 28.
The most common toxicities were ones that might be predictable based on prior experience with hypomethylating agents in general and the previous published data with ASCERTAIN, [which] included cytopenias and infectious complications, including febrile neutropenia and pneumonia.
With that said, the overall response rate was 57%, and that included 23% of patients who achieved a complete response. What we got to see in this abstract was the rate of transfusion independence, which is important in low-risk patients. We saw 48% of those patients who were receiving red cell transfusions became transfusion independent and 67% of patients who were receiving platelet transfusions became platelet and transfusion independent. The trial also looked at median overall survival and leukemia-free survival, and the median survival endpoints for those patients had not been met at 32 months.
What challenges remain to be addressed?
We talked about the treatment goal of...improving quality of life. These oral formulations may be an even bigger deal for low-risk patients who are often outside of our clinic, trying to live their life. By offering them an oral therapy, we are giving them the option to be treated at their home, reducing their visits with us, and hopefully, not only reducing infusion times for chemotherapy, but by offering them transfusion independence, they're going to reduce their time in our infusion chairs. That was one of the big points for me in this data…67% of patients coming off platelet transfusions and 48% off red cell transfusions.
This overall survival and leukemia free survival that exceeds 32 months is impressive. It is going to be interesting to see how this data matures [as we continue] to watch this patient population, and certainly, this gives us something to turn to for those patients that many of us might have been managing in clinic. They’re rare patients, but those patients who have isolated thrombocytopenia, more isolated anemia, this is reassuring data that allows us to apply the current FDA-approved label to those patients and offer them a new option.
Across the board there's a lot of excitement about the opportunity to use these oral [hypomethylating agents] as a backbone in combination trials, as well. Those are certainly ongoing, and there's a lot of exciting combinations that can be thought of. It gives us the opportunity in the future to be considering a completely oral regimen for our elderly, unfit patients.
This article was originally published on OncLive as “Oral Decitabine Plus Cedazuridine Combo Shows Promise in Lower-Risk MDS”