Decitabine 35mg / Cedazuridine 100mg tablets

Background/Objectives: Triple-negative breast cancer (TNBC) is an aggressive subtype lacking ER, PR, and HER2 expression, with limited targeted therapies and poor outcomes. Epigenetic dysregulation, particularly aberrant DNA methylation, is a key driver. Decitabine, a DNA methyltransferase inhibitor (DNMTi), shows promise by reactivating silenced tumor suppressor genes and modulating immune responses. This systematic review evaluates preclinical and clinical evidence on decitabine's efficacy, mechanisms, and translational potential in TNBC. Methods: A PRISMA-2020 compliant search of PubMed, EBSCO, Web of Science, and Semantic Scholar was conducted up to April 2025. Included studies assessed decitabine alone or in combination in TNBC preclinical or clinical settings. Risk of bias was assessed using QUIPS and RoB 2.0 tools. Results: Twenty-five studies were included. In vitro, decitabine-induced growth inhibition, apoptosis, and re-expression of silenced genes (such as BRCA1 and CDH1). In vivo, it reduced tumor burden and enhanced anti-tumor immunity through MHC-I, PD-L1, and STING pathway upregulation. Synergy was noted with anti-PD-1, HDAC inhibitors, and chemotherapy. Resistance mechanisms included persistent DNMT activity, low DCK, and miRNA-driven escape (miR-155-TSPAN5). Conclusions: Decitabine demonstrates strong preclinical and early clinical potential in TNBC via epigenetic reprogramming and immune activation. Future strategies should focus on biomarker-based selection and resistance mitigation.

Abstract licence: CC BY

IntroductionChronic myelomonocytic leukemia (CMML) is a biologically heterogeneous myelodysplastic/myeloproliferative neoplasm with limited disease-modifying treatment options beyond hypomethylating agents (HMAs) and allogeneic hematopoietic stem cell transplantation. Venetoclax, a selective BCL-2 inhibitor, is increasingly used off-label in CMML, but its CMML-specific efficacy and safety remain incompletely defined.MethodsWe conducted a systematic review and meta-analysis in accordance with PRISMA 2020. Eligible studies included adult patients with CMML treated with venetoclax-based regimens and reporting extractable CMML-specific outcomes. PubMed, Embase, Cochrane CENTRAL, conference proceedings, and trial registries were searched through August 2025. Random-effects meta-analyses of proportions were performed for complete remission (CR), marrow complete remission (mCR), and overall response rate (ORR).ResultsSeventeen publications representing nine unique studies were included, comprising 145 venetoclax-treated CMML patients. Most regimens combined venetoclax with azacitidine, decitabine, or oral decitabine-cedazuridine, with heterogeneous dosing schedules and frequent CYP3A-guided dose modifications. Responses typically occurred early, within one to two treatment cycles, but durability was generally modest. The pooled CR rate was 19.1% (95% CI: 9.4-34.9; I2 = 55%), the pooled mCR rate was 36.4% (95% CI: 24.7-50.0; I2 = 21%), and the pooled ORR was 71.9% (95% CI: 56.5-83.4; I2 = 56%). Venetoclax-based therapy was associated with substantial myelosuppression, including frequent grade ≥3 neutropenia and thrombocytopenia, with clinically relevant infectious complications. Early mortality was low in studies reporting short-term outcomes.ConclusionVenetoclax-based regimens demonstrate measurable but limited activity in CMML, with high overall response rates but low CR rates and modest durability. Prospective CMML-specific trials are needed to define optimal dosing, clarify comparative effectiveness, and identify patients most likely to benefit.

Abstract licence: CC BY

Hypomethylating agents (HMA) are indicated in the treatment of higher-risk myelodysplastic syndromes (MDS) and chronic myelomonocytic leukemia (CMML). The combination of hypomethylating agents with venetoclax (Ven) has demonstrated promising results in these diseases, although randomized clinical trials are needed for validation. In this retrospective study, we compared two matched cohorts of patients with MDS or CMML: one receiving oral decitabine-cedazuridine (DEC-C, n = 73) and one receiving DEC-C and Ven (DEC-C-Ven, n = 51), in three contemporary clinical trials. The aim is to determine the impact of the addition of Ven to HMA in MDS and CMML. Individuals were matched using a propensity score approach that was based on the IPSS-M score and age. All patients had excess blasts; 84% were diagnosed with MDS and 16% with CMML. Most patients had high- or very high-risk disease, according to the revised IPSS-R. The overall response rate was superior in the DEC-C-Ven cohort (90% vs 64%, P = 0.002). The median times to best response were 1.1 and 2.7 months for the DEC-C-Ven and DEC-C cohorts, respectively (P < 0.001). More patients underwent hematopoietic stem cell transplantation in the DEC-C-Ven cohort (47%) than in the DEC-C cohort (16%, P < 0.001). The 4- and 8-week mortality did not significantly differ between the DEC-C and DEC-C-Ven cohorts. Patients in the DEC-C-Ven cohort had a more profound neutropenia at days 15 and 21 of the first cycle. The median overall survival was 24 and 19 months for the DEC-C-Ven and DEC-C cohorts, respectively (P = 0.89), and the median event-free survival durations were 18 and 10 months (P = 0.026). In conclusion, the addition of Ven resulted in improved response rates and outcomes in specific subgroups; prospective clinical trials are needed to confirm these findings.

Abstract licence: CC BY-NC-ND 4.0

ABSTRACT Introduction Myelodysplastic syndromes/neoplasms (MDS) are a heterogenous group of myeloid cancers that impose a substantial negative impact on patient health-related quality of life. As MDS predominately affects older individuals, who are especially susceptible to the debilitating nature of the disease and its burdensome symptoms, treatment decisions should consider therapeutic value from multiple perspectives to balance clinical efficacy with patient-centered outcomes. This comprehensive approach is known as relative medical value. Areas covered Although improved outcomes have been observed with hypomethylating agents (HMAs) in patients with higher-risk MDS, parenteral administration of HMA requires frequent infusion clinic visits and is associated with substantial time burden, especially in older patients, impacting treatment persistence. Suboptimal use of HMAs in MDS may lead to poorer outcomes and higher healthcare costs, underscoring the need for patient-centered treatment options that improve persistence. Expert opinion Oral decitabine and cedazuridine (DEC-C) is an approved treatment for higher-risk MDS and may reduce patient burden associated with parenteral HMA therapy. Oral DEC-C has the potential to improve treatment persistence and clinical outcomes and reduce healthcare resource utilization and costs. This review integrates the available clinical, patient-centered, and economic evidence on the relative medical value of oral DEC-C treatment for MDS. GRAPHICAL ABSTRACT

Abstract licence: CC BY-NC-ND 4.0

A fixed dose oral combination (FDC) of decitabine and cedazuridine (Inqovi®), is being developed by Astex Pharmaceuticals (a subsidiary of Otsuka Pharmaceuticals) for the treatment of various cancers like myelodysplastic syndromes (MDS), chronic myelomonocytic leukaemia (CMML), acute myeloid leukaemia (AML), glioma and solid tumours. Decitabine, a DNA methyltransferase inhibitor approved for the treatment of MDS and CMML, is degraded by cytidine deaminase in the gastrointestinal tract and liver, thereby limiting oral bioavailability. Cedazuridine is a proprietary, patented cytidine deaminase inhibitor that, when added to decitabine, increases oral bioavailability of the drug. In July 2020, decitabine/cedazuridine received its first approval in the USA and Canada for the treatment of MDS and CMML. In the USA, it is indicated for use in adults with MDS and CMML, including previously treated and untreated, de novo and secondary MDS with the following French–American–British subtypes (refractory anaemia, refractory anaemia with ringed sideroblasts, refractory anaemia with excess blasts and CMML) and intermediate-1, intermediate-2 and high-risk International Prognostic Scoring System groups. Clinical studies for AML, glioma and solid tumours are underway in several countries worldwide. This article summarizes the milestones in the development of decitabine/cedazuridine leading to this first approval for the treatment of MDS and CMML.

Abstract licence: CC BY-NC 4.0