Efficacy and safety of dinaciclib vs ofatumumab in patients with relapsed/refractory chronic lymphocytic leukemia

Inhibition of Cyclin‐Dependent Kinase 5: A Strategy to Improve Sorafenib Response in Hepatocellular Carcinoma Therapy

“…Cdk5 can be pharmacologically targeted by Dinaciclib, a small molecule Cdk5 inhibitor that has shown promising anticancer effects with a manageable side‐effect profile in clinical trials. Dinaciclib is a well‐tolerated compound and has been successfully evaluated as therapy of chronic lymphocytic leukemia in phase III clinical trials and is currently under clinical investigation for the treatment of other types of leukemia . According to our study, Dinaciclib represents a promising therapeutic option for HCC that increases sorafenib efficiency and inhibits treatment escape.…”

The Emerging Role of Cyclin-Dependent Kinases (CDKs) in Pancreatic Ductal Adenocarcinoma

“…Pre-clinical testing of the substance showed acceptable toxicity and promising efficacy in mouse models and was well tolerated and active in phase I clinical trials [ 211 , 212 ]. Therefore, dinaciclib entered phase III clinical trials with refractory chronic lymphocytic leukaemia (CLL) [ 213 ]. In preclinical models for PDAC, monotherapy with dinaciclib inhibited growth, migration, and colony formation of pancreatic cancer cells through the blockage of cell cycle progression and reduction in Rb phosphorylation.…”

“…Although clinical studies in humans with pancreatic cancer and dinaciclib are rare, it has been extensively studied in other tumour entities. Dinaciclib is one of the few CDK-inhibitors, next to palbociclib and abemaciclib, which made it past phase II into phase III in CLL [ 213 ]. One of the most significant predicted benefits of dinaciclib over flavopiridol is better tolerance over longer timespans, especially in refractory patients [ 234 ].…”

“…Regarding phase III studies, dinaciclib was compared to ofatumumab, an anti-CD-20-antibody [ 259 ] in terms of efficacy and safety in relapsed or refractory CLL [ 213 ]. This study showed the promising antitumoural activity of dinaciclib in this hematologic neoplasia, with five times better overall response [ 213 ]. Currently, there is one already completed phase I study directed towards inoperable pancreatic cancer though there are no results published yet (ClinicalTrials.gov Identifier NCT01783171).…”

CDK9 inhibitors in acute myeloid leukemia

“…A randomized phase 3 study in which 42 patients with R/R CLL received treatment suggested promising antileukemic activity with dinaciclib relative to ofatumumab, an anti-CD20 monoclonal antibody (median progression-free survival of 13.7 months vs. 5.9 months, and overall response rate of 40% vs. 8.3%, respectively) [ 86 ]. The most common grade ≥ 3 adverse events experienced by patients receiving dinaciclib were neutropenia/reduced neutrophil counts/febrile neutropenia and thrombocytopenia.…”