Afatinib DimaleateGiotrif
Not recommended OncologyAuthority RequiredFirst-line line
First or subsequent line treatment of locally advanced (stage IIIB) or metastatic (stage IV) non-small cell lung cancer (NSCLC) with EGFR exon 19 deletion mutations.
1
Submissions
1 resub
2015–15
On the record
—
ICER range
Cost-min
Cost basis
Decision on record
- Meeting Jul 2015 Not recommended Monotherapy for patients with advanced or metastatic non-squamous type non-small cell lung cancer (NSCLC), either as a first line therapy or after failure of cytotoxic chemotherapy.
Access path
- TGA registered · Giotrif
TGA label narrower than the PBS population
- Jul 2015Not recommended
Proposed population restriction to exon 19 deletion mutations not consistent with previous PBAC recommendations for all…
RecommendedDeferredNot recommended
From the public summary
PBAC outcome
7.1 The PBAC did not recommend the more restricted listing of afatinib demaleate in patients with locally advanced or metastatic non-small cell lung cancer characterised by exon 19 deletion mutations of the epidermal growth factor receptor (EGFR) gene.PSD · Jul 2015
In making this recommendation, the PBAC considered that the data provided in the submission did not provide sufficient evidence to demonstrate that afatinib is associated with improved clinical outcomes for the EGFR exon 19 deletion subgroup, in comparison with gefitinib and with erlotinib.PSD · Jul 2015
Economic analysis
6.32 The re-submission presented a modelled economic evaluation (cost-utility analysis) based on point estimates of the PFS and OS hazard ratios for afatinib, compared with erlotinib or gefitinib, in the subgroup of NSCLC patients with exon 19 deletion EGFR mutations.PSD · Jul 2015
AFATINIB DIMALEATE 7.02.COM.20 the quantified differences in efficacy and safety that were proposed. The PSCR noted that the lack of statistically significant results could be expected given the small number of patients in the trials; however, it further stated that there is a “a clear trend towards improved overall survival with afatinib” and in terms of PFS, that “the results of the indirect comparison versus gefitinib showed a statistically significant …PSD · Jul 2015
Clinical claim
6.27 The re-submission described afatinib as having “improved clinical outcomes compared with the other EGFR TKIs (gefitinib and erlotinib) in patients with exon 19 deletion EGFR mutations”. In terms of safety, the re-submission claimed that the differences in the adverse event profiles of the EGFR TKIs means that it would be desirable to have a choice of TKIs in terms of managing the risks to individual patients.PSD · Jul 2015
The description in the re-submission that afatinib was associated with improved clinical outcomes compared with gefitinib and with erlotinib was not adequately supported, in terms of comparative effectiveness, by the evidence/analyses presented.PSD · Jul 2015
Financial management – risk sharing
6.54 The re-submission stated that “Boehringer Ingelheim remains willing to enter into a risk sharing arrangement with the Commonwealth, and is able to accept the other terms and conditions of the risk sharing arrangements for the other PBS listed EGFR tyrosine kinase inhibitors (EGFR TKIs), to the limited extent that these have been disclosed by the DoH to date”. A key aim of the re-submission was to request an SPA for afatinib. 26PSD · Jul 2015
Cost-effectiveness
ICER not stated; submission was based on cost-minimisation argument with comparators, but PBAC did not accept the proposal.
The PBAC considered the evidence provided in the minor re-submission and in the pre-PBAC response. The PBAC advised the Department that it did not accept that afatinib has unique characteristics compared to other available therapies for the treatment of patients with advanced or metastatic non-squamous NSCLC. PBAC · 2015
Economic model disputed
Decision context
PopulationAdults with locally advanced (stage IIIB) or metastatic (stage IV) non-squamous or not otherwise specified NSCLC with evidence of EGFR exon 19 deletion mutations, WHO/ECOG performance status 0–2, previously untreated or intolerant to another EGFR TKI.
Why it was knocked back
- Proposed population restriction to exon 19 deletion mutations not consistent with previous PBAC recommendations for all activating EGFR mutations; inability to obtain special pricing arrangement (SPA) for afatinib; PBAC did not accept that afatinib has unique characteristics compared to erlotinib and gefitinib; exchangeability concerns regarding indirect comparisons between trials due to different chemotherapy regimens and baseline characteristics; requested listing restriction to ECOG performance status 0–2 not supported by trial populations (LUX Lung 3 and 6 enrolled ECOG 0–1 only)
Submission history
| Decided | Outcome | Comparator | ICER | Evidence |
|---|---|---|---|---|
| Jul 2015 | Not recommended | erlotinib and gefitinib | — | RCT · PFS |
Similar precedents
Regulatory · TGA
Label narrower than PBS population — PBAC restricts to exon 19 deletion only, excluding L858R substitution mutations covered by TGA label.