Arsenic TrioxideArsenic trioxide ? AFT
First-line treatment of acute promyelocytic leukaemia (APL) in combination with all-trans retinoic acid (ATRA) with or without chemotherapy, for both induction of remission and consolidation therapy.
Decision on record
- Meeting Mar 2009 Recommended Anti- cancer drug
Access path
- TGA registered · Arsenic trioxide ? AFT
TGA label equal than the PBS population
- Mar 2009Recommended · restricted
Evidence: RCT → Single-arm
- Mar 2009Recommended · restricted
Evidence: RCT → Single-arm
- Nov 2015Recommended
Comparator changed: all-trans retinoic acid (ATRA) and intensive chemotherapy →…
- PBS listing · Authority Required
From the public summary
7.1 The PBAC recommended the extension of the current listing of arsenic trioxide to include the first line treatment of patients with acute promyelocytic leukaemia (APL).PSD · Nov 2015
The recommendation was made on the basis the cost-effectiveness of arsenic trioxide in combination with ATRA+/-chemotherapy over ATRA+chemotherapy alone.PSD · Nov 2015
6.36 The submission presented a modelled cost-effectiveness analysis, in which the treatment effects were based on an unadjusted indirect comparison of two single-arm studies (APML4 and APML3) including both low-intermediate and high risk patients.PSD · Nov 2015
Results were extrapolated beyond the study duration to a lifetime. As noted earlier, the treatment regimen in APML4 was only relevant to the regimen proposed for the high risk APL patient subgroup. APML3 may not represent the current non-ATO based treatment regimen for APL and the treatment protocol appears less intensive than regimens recommended in current guidelines.PSD · Nov 2015
6.31 In newly diagnosed patients with low-intermediate risk APL, the submission described a regimen of ATO+ATRA, without chemotherapy or maintenance therapy, as superior in terms of comparative effectiveness and non-inferior in terms of comparative safety relative to a regimen of ATRA+chemotherapy regimen, including maintenance therapy.PSD · Nov 2015
6.32 The ESC considered that this claim was adequately supported in regard to the comparative effectiveness and short-term safety of the specific regimens compared in Lo-Coco 2013. No long-term safety data were available. High risk APLPSD · Nov 2015
Cost-effectiveness
ICER not stated in public text; economic evaluation presented but document does not provide numeric ICER value
The PBAC agreed that the assumptions and the extrapolation used in the modelled evaluation were highly uncertain, and the results of the economic evaluation should be interpreted with caution. PBAC · 2009
Decision context
PopulationNewly diagnosed patients with previously untreated acute promyelocytic leukaemia (APL), characterised by t(15:17) translocation or PML/RAR-α gene expression, treated with ATO+ATRA±chemotherapy
Why it was knocked back
- uncertain effectiveness in high-risk patients (single-arm studies with high risk of bias), comparator regimen (APML3) did not represent current Australian clinical practice, potential inappropriate initiation of ATO in PML/RAR-α negative patients, insufficient evidence regarding maximum duration of induction therapy, regimens in APML4 not simply addition of ATO to APML3
Submission history
| Decided | Outcome | Comparator | ICER | Evidence |
|---|---|---|---|---|
| Nov 2015 | Recommended | ATRA+chemotherapy (APML3 regimen used in economic model) | — | RCT · Event-free survival |
| Mar 2009 | Recommended · restricted | all-trans retinoic acid (ATRA) and intensive chemotherapy | $45k–75k | RCT · Overall survival at two years, clinical complete remission |
| Mar 2009 | Recommended · restricted | all-trans retinoic acid (ATRA) and intensive chemotherapy | $15k–75k | Single-arm · OS |
Similar precedents
Regulatory · TGA
Label equal than PBS population — Both specify first-line APL with t(15;17)/PML-RAR-α, previously untreated, with ATO+ATRA±chemotherapy for induction and consolidation.