Venetoclax in the treatment of acute myeloid leukemia
Venetoclax ( Venclexta ) in newly-diagnosed AML patients who are ineligible for intensive chemotherapy is supported by data from a series of trials including two phase 3 trials, VIALE-A ( M15-656 ) and VIALE-C ( M16-043 ).
Venetoclax is a first-in-class medicine that selectively binds and inhibits the B-cell lymphoma-2 ( BCL-2 ) protein.
In some blood cancers, BCL-2 prevents cancer cells from undergoing their natural death or self-destruction process, called apoptosis. Venetoclax targets the BCL-2 protein and works to help restore the process of apoptosis.
A total of 431 patients were randomized in the double-blind, placebo-controlled, multicenter, phase 3 VIALE-A trial, which has evaluated the efficacy and safety of Venetoclax in combination with Azacitidine ( n=286 ) in patients with AML who are ineligible for standard induction therapy versus Azacitidine in combination with placebo ( n=145 ).
The primary endpoint was overall survival ( OS ).
The Venetoclax plus Azacitidine combination showed a median overall survival of 14.7 months ( 95% CI: 11.9, 18.7 ) versus 9.6 months ( 95% CI: 7.4, 12.7 ) with Azacitidine in combination with placebo.
The study also met its secondary endpoints, with the Venetoclax combination arm resulting in a complete response ( CR ) rate of 37% ( 95% CI: 31, 43 ) and a CR+CRh rate of 65% ( 95% CI: 59, 70) compared to a CR rate of 18% ( 95% CI: 12, 25 ) and a CR+CRh rate of 23% ( 95% CI: 16, 30 ) in the placebo arm.
The median time to first response of CR or CRh was 1.0 months ( range: 0.6 to 14.3 months ) with Venetoclax in combination with Azacitidine.
The median duration of treatment was 7.6 months ( range: less than 0.1 to 30.7 months ) in the Venetoclax arm.
The most frequent adverse reactions ( greater than or equal to 30% with a difference between arms of 5% or more ) for patients taking Venetoclax in combination with Azacitidine were mostly hematologic and gastrointestinal in nature and consisted of, nausea ( 44% ), diarrhea ( 43% ), febrile neutropenia ( 42% ), musculoskeletal pain ( 36% ), fatigue ( 31% ), and vomiting ( 30% ).
Serious adverse reactions were reported in 83% of patients in the Venetoclax arm, with the most frequent serious adverse reactions ( 5% or more ) being febrile neutropenia ( 30% ), pneumonia ( 22% ), sepsis ( excluding fungal, 19% ) and hemorrhage ( 6% ).
A total of 211 patients were enrolled and treated in the randomized, double-blind, placebo-controlled, multicenter, phase 3 VIALE-C trial, which evaluated the efficacy and safety of Venetoclax in combination with LDAC [ Low-Dose Cytarabine ] ( n=143 ) versus placebo with LDAC ( n=68 ).
The primary endpoint was overall survival.
Venetoclax in combination with LDAC did not significantly improve overall survival versus placebo in combination with LDAC.
The hazard ratio for overall survival was 0.75 ( 95% CI: 0.52, 1.07 ); p-value 0.114.
The median overall survival for Venetoclax in combination with LDAC arm was 7.2 months ( 95% CI: 5.6, 10.1 ) and for Placebo + LDAC arm was 4.1 months ( 95% CI: 3.1, 8.8 ).
Efficacy was based on the rate of CR and duration of CR with supportive evidence of rate of CR+CRh, duration of CR+CRh, and the rate of conversion from transfusion dependence to transfusion independence.
The CR rate in the Venetoclax in combination with LDAC arm was 27% ( 95% CI: 20%, 35% ) with a median duration of CR of 11.1 months ( 95% CI: 6.1, - ), and the CR rate in the placebo arm was 7.4% ( 95% CI: 2.4%, 16% ) with a median duration of CR of 8.3 months ( 95% CI: 3.1, - ).
The CR+CRh rate in the Venetoclax in combination with LDAC arm was 47% ( 95% CI: 39%, 55% ) and in the placebo arm was 15% ( 95% CI: 7.3%, 25% ) with a median duration of CR+CRh of 11.1 months with Venetoclax in combination with LDAC and 6.2 months with LDAC in combination with placebo.
The median time to first response of CR or CRh was 1.0 month ( range: 0.7 to 5.8 months ) with Venetoclax in combination with LDAC.
The most frequent adverse reaction ( 30% or more with a difference between arms of 5% or more ) for patients taking Venetoclax in combination with LDAC was nausea ( 42% ).
Serious adverse reactions were reported in 65% of patients in the Venetoclax arm, with the most frequent ( 10% or more ) being pneumonia ( 17% ), febrile neutropenia ( 16% ), and sepsis ( excluding fungal; 12% ). ( Xagena )
Source: Abbvie, 2020
UCSD ( University of California San Diego ) researchers have identified the molecular mechanism activated by the presence of tetrahydrocannabinol...
European Commission has approved Venclyxto plus Gazyvaro for adults with previously untreated chronic lymphocytic leukaemia
The European Commission has approved Venclyxto ( Venetoclax ) in combination with Gazyvaro ( Obinutuzumab ) for the treatment of...
monarchE trial: Abemaciclib given with endocrine therapy has shown improvement compared to endocrine therapy alone in people whose HR+ HER2- early breast cancer is at a high risk of recurrence
Abemaciclib ( Verzenio ) in combination with standard adjuvant endocrine therapy has met the primary endpoint of invasive disease-free...
Venclexta as a chemotherapy-free combination regimen for previously untreated chronic lymphocytic leukemia patients, approved by FDA
The U.S. Food and Drug Administration ( FDA ) has approved Venclexta ( Venetoclax ) in combination with Obinutuzumab (...
Venetoclax chemotherapy-free combination regimen for patients with previously untreated chronic lymphocytic leukemia
Data from the CLL14 trial, the first randomized clinical trial to examine stopping an oral-based, chemotherapy-free combination after 12 months...
The PI3K/AKT/mTOR pathway is an intracellular signalling pathway that regulates cell activation, proliferation, metabolism and apoptosis. Increasing body of data...
Acute myeloid leukemia ( AML ) remains a highly resistant disease to conventional chemotherapy, with a median survival of only...
Combination therapy based on Tafinlar and Mekinist for adjuvant treatment of BRAF V600 mutation-positive melanoma: approved in European Union
The European Commission has approved Tafinlar ( Dabrafenib ) in combination with Mekinist ( Trametinib ) for the adjuvant treatment...
In 2016, the National Institute for Health and Care Excellence ( NICE ) approved the use of Belimumab ( Benlysta...