NeratinibNERLYNX
Not recommended OncologyAuthority RequiredSecond-line line 💬 consumer voice
Extended adjuvant treatment of adult patients with HER2-positive, hormone receptor positive, early breast cancer who have completed prior adjuvant trastuzumab-based therapy within the past 12 months.
2
Submissions
1 resub
2019–19
On the record
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ICER range
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Cost basis
Decisions on record
- Meeting Nov 2019 Not recommended Neratinib is indicated for the extended adjuvant treatment of adult patients with early-stage human epidermal growth factor receptor-2 (HER2) overexpressed/ amplified breast cancer, to follow adjuvant trastuzumab based therapy.
- Meeting Mar 2019 Not recommended Early breast cancer
Access path
- TGA registered · NERLYNX
TGA label narrower than the PBS population
- Mar 2019Not recommended
vs usual care/placebo
- Nov 2019Not recommended
unclear clinical place in therapy with emerging treatments (T-DM1, pertuzumab), no new clinical data or OS data as…
RecommendedDeferredNot recommended
From the public summary
PBAC outcome
7.1 The PBAC did not recommend the listing of neratinib for extended adjuvant treatment of adult patients with HER2+, HR+ eBC who have completed prior adjuvant trastuzumab-based therapy within the past 12 months. The PBAC considered that the clinical place of neratinib was reduced to a limited and diminishing population, given the changing landscape for the treatment of HER2+ eBC.PSD · Nov 2019
7.2 The PBAC noted that input from 37 individuals and two organisations (BCNA and MOGA) was received in support of a PBS listing for neratinib. The BCNA noted that there was increasing use of neoadjuvant treatment in eBC however believed that there would be a patient population, albeit a small population, who would benefit from treatment with neratinib in the adjuvant setting following trastuzumab 33PSD · Nov 2019
Economic analysis
6.41 The resubmission presented a cost-utility and cost-effectiveness analysis comparing neratinib to usual care/placebo, based on the ExteNET trial, Australian mortality data and data from published literature. The resubmission implemented a modelled evaluation. The resubmission did not present a stepped economic evaluation.PSD · Nov 2019
6.42 The resubmission outlined a changed proposed clinical management algorithm compared to the original submission. This was not reflected in the economic model which does not exclude higher risk patients who were included in the ExteNET trial.PSD · Nov 2019
Clinical claim
Although the documentation provided with the model was improved from the original submission and some of the PBAC’s concerns with the model were addressed, some issues were not addressed by the resubmission. Changes to the model structure, assumptions, inputs and inconsistency with the clinical algorithm introduced additional uncertainty to the economic evaluation. The uptake and financial estimates were still considered to be overestimated.PSD · Nov 2019
6.33 The resubmission described neratinib as superior in terms of effectiveness compared with placebo in patients with HER2+ eBC. The resubmission also described neratinib as inferior in terms of safety compared to placebo. This is unchanged from the original submission. 22PSD · Nov 2019
Consumer comments
6.2 The PBAC noted and welcomed the input from individuals (37) and organisations (2) via the Consumer Comments facility on the PBS website. The PBAC noted the comments reported different levels of severity for the adverse effects associated with neratinib. The side effects included diarrhoea, tiredness and fatigue, dry skin, cramping, nose bleeds, brittle nails, lack of appetite and weight loss.PSD · Nov 2019
6.3 The PBAC noted the advice received from Breast Cancer Network Australia (BCNA) clarifying the likely use of neratinib in clinical practice. The BCNA maintained its support for neratinib. The BCNA acknowledged the increasing use of neoadjuvant treatment in eBC however believed that there would be a patient population, albeit a small population, who would benefit from treatment with neratinib in the adjuvant setting following trastuzumab treatment.PSD · Nov 2019
Cost-effectiveness
ICER not stated in this PSD; economics section was incomplete in provided text.
Decision context
PopulationAdult patients with HER2+, HR+, early breast cancer who have completed prior adjuvant trastuzumab-based therapy within the past 12 months.
Why it was knocked back
- unclear clinical place in therapy with emerging treatments (T-DM1, pertuzumab), no new clinical data or OS data as requested, substantial risk of severe diarrhoea versus small and uncertain benefit, economic analysis highly uncertain, overestimated uptake and financial estimates, inconsistencies between clinical algorithm, TGA indication, proposed restriction, and ExteNET trial population
Submission history
| Decided | Outcome | Comparator | ICER | Evidence |
|---|---|---|---|---|
| Nov 2019 | Not recommended | placebo/usual care | — | RCT · Invasive disease-free survival |
| Mar 2019 | Not recommended | usual care/placebo | — | RCT · DFS |
Clinical evidence
| Trial | Phase | N | Primary outcome | Status |
|---|---|---|---|---|
| ExteNET | Ph 3 | 2,840 | Invasive Disease-free Survival (iDFS) in Neratinib Arm Compared to Placebo Arm at Year 2 | completed |
Consumer voice
37 individuals and 2 organisations (including Breast Cancer Network Australia) provided input on neratinib. Most comments reported manageable side effects that did not significantly impact quality of life, though some discontinued due to severe diarrhoea. Overall, consumers supported neratinib as a way to prevent cancer recurrence, with willingness to tolerate initial side effects for long-term be
approximately three quarters of the comments reported minimal or manageable side effects (many described the side effects as initially difficult but then became manageable over the course of treatment) Consumer comments · PSD
side effectsquality of lifetreatment burdenunmet needaccess to treatmentsurvival benefit
Similar precedents
Regulatory · TGA
Label narrower than PBS population — PBAC restricts to hormone receptor positive patients and requires completion of prior trastuzumab within 12 months; TGA label has neither restriction.