Venclexta-Cytarabine Fails to Significantly Prolong Life in Untreated AML Patients, Trial Shows

Venclexta-Cytarabine Fails to Significantly Prolong Life in Untreated AML Patients, Trial Shows

First-line treatment with a combination of Venclexta (venetoclax) and a low dose of cytarabine failed to significantly extend the survival of people with acute myeloid leukemia (AML) who were ineligible for intensive chemotherapy, as compared with treatment with cytarabine alone, AbbVie said.

The VIALE-C Phase 3 clinical trial (NCT03069352) demonstrated that the median overall survival is 7.2 months for patients treated with the Venclexta combo, and 4.1 months for patients given cytarabine alone.

Although the trial missed its primary efficacy goal — a statistically significant improvement in overall survival — its results indicate that combination therapy with Venclexta has clinical activity for some AML patients.

For now, Venclexta maintains its indication for AML patients whose age or additional medical conditions preclude the use of standard chemotherapy.

“We remain committed to AML patients and our research in AML and other blood cancers,” Neil Gallagher, MD, PhD, AbbVie’s chief medical officer, said in a press release.

“The study results, while not statistically significant, are indicative of the clinical activity of venetoclax [Venclexta] in combination with low-dose cytarabine,” Gallagher said.

Venclexta is an oral targeted therapy developed and marketed by AbbVie and Genentech to treat certain blood cancers. It was approved by the U.S. Food and Drug Administration (FDA) in 2018 to treat people with AML who are 75 or older, or who have health conditions that preclude the use of standard chemotherapy.

In these patients, Venclexta is used in combination with Vidaza (azacitidine), Dacogen (decitabine), or low-dose cytarabine.

The FDA accepted the medicine’s label for AML under accelerated approval, based on promising response rates in two open-label Phase 1/2 trials (NCT02287233 and NCT02203773). This means the continued permission to use the medicine for AML may depend on the verification and description of clinical benefit in confirmatory trials.

If the confirmatory trial shows that a therapy actually provides a clinical benefit, the FDA grants traditional approval to the treatment; but if the trial fails to show it, the FDA could remove the treatment from the market for that indication.

The VIALE-C study evaluated the safety and efficacy of Venclexta, in combination with a low dose of the chemotherapy agent cytarabine, for treating newly diagnosed patients with AML who could not be treated by intensive chemotherapy.

Some 210 people were assigned to either Venclexta plus low dose cytarabine (143 patients) or a placebo in combination with low dose cytarabine (68 patients). The primary goal was to determine if the Venclexta combo significantly extended overall survival.

After a median follow-up time of 12 months, treatment with Venclexta combination had yielded a 25% lower risk of death compared with low-dose cytarabine alone. This result was not statistically significant, so the trial failed to achieve its primary endpoint.

An additional six months of follow-up, however, demonstrated a better median survival in the group of those treated with Venclexta plus low-dose cytarabine: a median of 8.4 months, significantly better than the 4.1 months seen with cytarabine only.

The study had other secondary measures of efficacy, including complete remission rates — the percentage of patients who were cleared of all detectable signs of cancer.

Venclexta combo led to a complete remission of 27.3% of the patients, while treatment with cytarabine led to a similar response in only 7.4%.

Complete remission including patients with and without complete recovery of blood cells was 47.6% in the group treated with Venclexta, and 13.2% in the group treated with cytarabine only.

The safety profile of the combination was consistent with results from the prior Phase 1/2 studies that led to the combination’s approval for AML patients.

The most common adverse events were lowered blood cell counts, including febrile neutropenia (fever associated with low counts of neutrophils, a type of white blood cell), neutropenia (low counts of neutrophils), thrombocytopenia (low platelet counts), and anemia.

VIALE-C results have been provided to the FDA and other regulatory agencies. Abbvie said it will continue to work alongside the agencies to ensure that Venclexta remains an appropriate option for AML. At this time, the medicine’s indications remain unchanged.

An additional Phase 3 trial, VIALE-A (NCT02993523), is ongoing to further evaluate the efficacy of Venclexta in combination with Vidaza for newly diagnosed AML.

Venclexta is not approved for the treatment of AML in Europe.