VIALE-A: trial | Bending the Curve: Trial by Trial

VIALE-A

Azacitidine and venetoclax in previously untreated acute myeloid leukemia

Population

Previously untreated AML in patients ineligible for standard induction therapy because of coexisting conditions, age 75 years or older, or both (median age 76 years, range 49 to 91)

Design

Randomized, double-blind, placebo-controlled phase 3 trial. Azacitidine 75 mg per square meter on days 1 to 7 of each 28-day cycle plus venetoclax (target dose 400 mg daily) or matching placebo. Primary end point: overall survival. ClinicalTrials.gov lists 443 enrolled participants; the paper's intention-to-treat population is 431.

Primary endpoint

Arms

Azacitidine + venetoclax (experimental, n = 286): Azacitidine 75 mg/m2 days 1-7 per 28-day cycle plus venetoclax (target dose 400 mg daily)
Azacitidine + placebo (control, n = 145): Azacitidine 75 mg/m2 days 1-7 per 28-day cycle plus matching placebo

People

DiNardo CD

OSHR 0.66 (95% CI 0.52–0.85)Δ median OS+5.1 monthsΔ CR+18.8 pointsΔ CR+CRi+38.1 points

Show the numbers

Results reported for VIALE-A
Endpoint	Analysis	Azacitidine + venetoclax	Azacitidine + placebo	Effect
OS	primarymedian follow-up 20.5 monthsDiNardo 2020	median 14.7 months	median 9.6 months	HR 0.66 (95% CI 0.52–0.85)P<0.001The abstract gives the intention-to-treat population as 431 patients (286 and 145).
CR	primaryDiNardo 2020	36.7%	17.9%	P<0.001
CR+CRiComposite complete remission: complete remission or complete remission with incomplete hematologic recovery	primaryDiNardo 2020	66.4%	28.3%	P<0.001

Results reported for VIALE-A
Endpoint	Analysis	Azacitidine + venetoclax	Azacitidine + placebo	Effect
OS	primarymedian follow-up 20.5 monthsDiNardo 2020	median 14.7 months	median 9.6 months	HR 0.66 (95% CI 0.52–0.85)P<0.001The abstract gives the intention-to-treat population as 431 patients (286 and 145).
CR	primaryDiNardo 2020	36.7%	17.9%	P<0.001
CR+CRiComposite complete remission: complete remission or complete remission with incomplete hematologic recovery	primaryDiNardo 2020	66.4%	28.3%	P<0.001

Hazard ratio (95% CI) by endpoint. Values below 1 favour the experimental arm.

Data table

Endpoint	HR	95% CI
OS	0.66	0.52–0.85

Illustrative — modelled from reported values, not trial data. OS, primary.

Show curves

Azacitidine + venetoclax (experimental)
Azacitidine + placebo (control)

Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.

Data table (modelled values)

Months	Azacitidine + venetoclax	Azacitidine + placebo
0	100.0%	100.0%
9	65.4%	52.2%
18	42.8%	27.3%
28	26.7%	13.2%
37	17.5%	6.9%

Appears in

2018 Venetoclax with azacitidine for unfit AML (VIALE-A)

Sources

DiNardo CD, Jonas BA, Pullarkat V, Thirman MJ, Garcia JS, Wei AH, et al. Azacitidine and Venetoclax in Previously Untreated Acute Myeloid Leukemia. N Engl J Med. 2020;383(7):617-629.
PubMed DOI