The TGA has approved the provisional registration of venetoclax as part of combination therapy for patients with newly diagnosed AML who are ineligible for intensive chemotherapy.

The extension of indication for the BCL-2 inhibitor (Venclexta – 10 mg, 50 mg and 100 mg film coated tablets) from its initial use in CLL is supported by the recent findings of the phase 3 VIALE trials.

VIALE-A randomised 431 elderly patients from 75 years to either azacitidine plus venetoclax or azacitidine plus placebo.

The study, published recently in NEJM, found overall survival was longer (14.7 v 9.6 months) and the incidence of remission was higher (66% v 28%) among patients who received venetoclax.

Similarly, the VIALE-C study randomised patients ≥75 years or younger adults with comorbidities precluding intensive chemotherapy to either low-dose cytarabine plus venetoclax or cytarabine plus placebo.

The study, published in Blood earlier this year, found improved complete remission rates (48% v 13-15%) and longer overall survival (8.4 v 4.1 months) favoured the addition of venetoclax.

Professor Andrew Wei, lead author on VIALE-C, told the limbic the drug was currently available in Australia for AML at a cost.

“The next step will be to see if the drug will be [PBS] reimbursed,” he said.

“In the meantime, there is an investigator initiated trial that has commenced in the ALLG called AML M25 or INTERVENE that will make drug freely available to patients.”

And there was the promise of further expanding the indication.

Professor Wei, from the Alfred Hospital and Monash University, highlighted a feasibility trial of venetoclax in combination with modified intensive chemotherapy in fitter patients with AML which had demonstrated safety and tolerability as well as evidence of efficacy.

The phase 1b study, published in JCO, enrolled 51 patients either ≥ 65 years with newly diagnosed de novo or secondary AML without prior exposure to intensive chemotherapy or ≥ 60 years with monosomal karyotype.

The maximum tolerated dose was not determined despite venetoclax doses ranging from 50 to 600 mg.

The overall response rate (ORR) was 72% with complete remission (CR) in 41% and CR with incomplete count recovery in 31%.

Sub-groups of patients had higher ORR such as de novo AML at 97%.

The findings pave “…the way for future investigation of venetoclax in combination with intensive chemotherapy in younger patients with AML,” the study concluded.

In its assessment report for venetoclax, the TGA notes that the median age at diagnosis of AML is 69 years, with older patients showing a diminished response to chemotherapy, low remission rates and short overall survival. Currently, guidelines endorsed by Australian cancer groups recommend that elderly patients and those with significant co-morbidities receive best supportive care (BSC) or palliative systemic treatment.

The TGA says continued approval of the indication will depends on verification and description of benefit in confirmatory trials.