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CetuximabErbitux

Recommended OncologyAuthority RequiredFirst-line | Second-line line 💬 consumer voice

Treatment of metastatic colorectal cancer (mCRC) in RAS wild-type patients, including first-line treatment in combination with chemotherapy, second-line treatment following first-line chemotherapy or pembrolizumab, and BRAF V600E variant mCRC in combination with encorafenib. Also for squamous cell cancer of the larynx, oropharynx or hypopharynx concomitant with radiotherapy.

13
Submissions
10 resub
2005–24
On the record
$15k–200k
ICER range
8 sourced ICERs · 2005–2016
Cost-min
Cost basis

Decisions on record

13 decisions
  • Meeting Mar 2024 Recommended Metastatic colorectal cancer (mCRC)
  • Meeting Nov 2021 Withdrawn Recurrent or metastatic squamous cell carcinoma of the head and neck no PSD
  • Meeting Mar 2018 Recommended Recurrent or metastatic squamous cell carcinoma of the head and neck
  • Meeting Nov 2016 Not recommended Cetixumab is indicated for the treatment of patients with epidermal growth factor receptor (EGFR)-expressing, RAS wild-type metastatic colorectal cancer; and for the treatment of patients with squamous cell cancer of the head and neck.
  • Meeting Mar 2016 Not recommended Recurrent and/or metastatic squamous cell carcinoma of the head and neck
  • Meeting Nov 2014 Recommended 100 mg/20 mL injection, 1 x 20 mL vial 500 mg/100 mL injection, 1 x 100 mL vial Erbitux® Merck Serono Australia Pty Ltd Change to listing (Major submission) Colorectal cancer Section 100 (Efficient Funding of Chemotherapy) Authority Required (STREAMLINED) listing for the first line treatment of meta
  • Meeting Jul 2010 Recommended Anti-cancer drug
  • Meeting Mar 2010 Not recommended Cancer treatment
5 earlier decisions
  • Jul 2009 Not recommended Treatment of patients with metastatic colorectal cancer that has been demonstrated to express epidermal growth factor receptor (EGFR) and whose disease has progressed or is refractory to irinotecan based therapy. Cetuximab can be used at the doses recommended either in combination with irinotecan or no PSD
  • Mar 2009 Not recommended Treatment of patients with metastatic colorectal cancer that has been demonstrated to express epidermal growth factor receptor (EGFR) and whose disease has progressed or is refractory to irinotecan based therapy. Cetuximab can be used at the doses recommended either in combination with irinotecan or
  • Nov 2008 Not recommended Treatment of patients with metastatic colorectal cancer that has been demonstrated to express epidermal growth factor receptor (EGFR) and whose disease has progressed or is refractory to irinotecan based therapy. Cetuximab can be used at the doses recommended either in combination with irinotecan or
  • Mar 2008 Recommended Cancer no PSD
  • Mar 2008 Recommended Cancer no PSD

Access path

13 submissions · public record
  1. TGA registered · Erbitux

    TGA label narrower than the PBS population

  2. Nov 2005
    Not recommended

    uncertain clinical benefit, unacceptable and uncertain cost-effectiveness, unenforceable continuation rule with risk of…

  3. Nov 2005
    Not recommended

    uncertain clinical benefit (no head-to-head trial, survival gain uncertain across single-arm studies), unacceptable and…

  4. ↻ resubmitted
    Mar 2007
    Recommended · restricted

    ICER dropped $200,000 → $45,000 (-78%)

  5. Nov 2008
    Recommended

    ICER rose $45,000 → $200,000 (+344%)

  6. Mar 2009
    Not recommended

    high and uncertain cost-effectiveness, uncertain overall survival benefit based on post-hoc analysis of KRAS wild-type…

  7. Mar 2010
    Not recommended

    high and uncertain cost-effectiveness, uncertain survival benefit, inconclusive evidence for K-RAS as a treatment…

  8. ↻ resubmitted
    Jul 2010
    Recommended · restricted

    Comparator changed: bevacizumab in combination with FOLFIRI or FOLFOX → best supportive…

  9. Jul 2010
    Recommended · restricted

    Comparator changed: bevacizumab in combination with FOLFIRI or FOLFOX → best supportive…

  10. Nov 2014
    Recommended · restricted

    Comparator changed: best supportive care → bevacizumab + FOLFIRI

  11. Mar 2016
    Not recommended

    Comparator changed: bevacizumab + FOLFIRI → platinum-based chemotherapy alone

  12. Nov 2016
    Not recommended

    PBAC did not recommend listing based on uncertain magnitude of clinical benefit, likely high and unacceptable…

  13. ↻ resubmitted
    Mar 2018
    Recommended · restricted

    Comparator changed: platinum-based chemotherapy (cisplatin or carboplatin and…

  14. Mar 2024
    Recommended

    Evidence: RCT → Meta-analysis

  15. PBS listing · Authority Required
RecommendedDeferredNot recommended

From the public summary

Verbatim · PSD text · may span indications
PBAC outcome
5.1 The PBAC recommended increasing the maximum amount for the current listings of cetuximab to allow an alternative dosing regimen of 500 mg per m2 body surface area (BSA) once every two weeks in addition to the current dosing schedule of 400 mg per m2 BSA on week 1 followed by 250 mg per m2 BSA once every week for the treatment of metastatic colorectal cancer (mCRC). 7PSD · Mar 2024
5.2 The PBAC considered that it is reasonable to amend all current cetuximab listings for mCRC to increase the maximum amount for initial treatment from 880 mg to 1100 mg and for continuing treatment from 550 mg to 1100 mg to allow the 500 mg Q2W dosing regimen. This decision aligns with its previous approach to minimise additional item code creation when providing a new dosing regimen.PSD · Mar 2024
Economic analysis
4.10 The submission did not request changes to the current effective approved ex- manufacturer prices (AEMP) of cetuximab.PSD · Mar 2024
4.11 The proposed dispensed price for maximum amount (DPMA) for the requested maximum amount of 1100 mg was based on the current ex-manufacturer prices per 100 mg vial and 500 mg vial using the most efficient combination of cetuximab vials (1 x 100 mg vial and 2 x 500 mg vials).PSD · Mar 2024
Clinical claim
4.7 The submission claimed that, based on the clinical evidence presented, the Q2W dosing regimen of cetuximab for mCRC is non-inferior to the current Q1W dosing regimen in terms of comparative effectiveness and comparative safety.PSD · Mar 2024
4.8 The PBAC considered that the claim of non-inferior effectiveness was adequately supported by the clinical data.PSD · Mar 2024
Consumer comments
4.3 The MOGA expressed support for the cetuximab submission seeking the addition of the fortnightly dosing regimen. 3PSD · Mar 2024
Financial management – risk sharing
6.58 The resubmission proposed a special pricing arrangement consisting of a rebate of ''''''''% based on the published ex-manufacturer price. This was increased from the '''''''''% rebate proposed in the previous submission. Moreover, the sponsor proposed a risk-sharing arrangement with a ''''''% rebate above a subsidisation cap of ''''' infusions per RM SCCHN patient.PSD · Mar 2018

Cost-effectiveness

8 sourced ICERs · 2005–2016

This is a Category 4 submission for an alternative dosing regimen (500 mg Q2W versus 250 mg Q1W) of an already-listed drug. No economic evaluation or ICER was required; the submission presented cost comparison only.

The PBAC noted that the submission estimated a total net saving to the PBS/RPBS of $3.9 million over the first 6 years of listing, based on no changes to the current AEMP of cetuximab vials. PBAC · 2024
ICER uncertain ×5ICER / price too high ×2Economic model disputed ×4Immature survival dataSurrogate endpoint ×2Cost-effectiveness accepted ×2

Decision context

PopulationPatients with RAS wild-type metastatic colorectal cancer receiving cetuximab as first-line (in combination with chemotherapy) or second-line (following first-line chemotherapy or pembrolizumab) treatment, or BRAF V600E variant mCRC in combination with encorafenib.

Submission history

13 entries
DecidedOutcomeComparatorICEREvidence
Mar 2024 Recommended Meta-analysis · OS | PFS | ORR
Mar 2018 Recommended · restricted platinum-based chemotherapy (cisplatin or carboplatin) plus 5-fluorouracil (5-FU) RCT · OS
Nov 2016 Not recommended platinum-based chemotherapy (cisplatin or carboplatin and 5-fluorouracil) $75k–105k RCT · OS
Mar 2016 Not recommended platinum-based chemotherapy alone RCT · OS
Nov 2014 Recommended · restricted bevacizumab + FOLFIRI RCT · ORR
Jul 2010 Recommended · restricted best supportive care $45k–75k RCT · OS
Jul 2010 Recommended · restricted best supportive care $45k–75k RCT · OS
Mar 2010 Not recommended bevacizumab in combination with FOLFIRI or FOLFOX RCT · PFS
Mar 2009 Not recommended best supportive care $45k–200k RCT · OS
Nov 2008 Recommended best supportive care $45k–200k RCT · OS
Mar 2007 Recommended · restricted radiotherapy alone $15k–45k RCT · loco-regional control, overall survival
Nov 2005 Not recommended usual care consisting of best supportive care (BSC) and the chemotherapy agents currently used third line, capecitabine, $75k–105k RCT · OS
Nov 2005 Not recommended usual care consisting of best supportive care (BSC) and third-line chemotherapy agents (capecitabine, 5-FU + mitomycin C $45k–200k Single-arm · ORR

Codependent tests

MSAC
ServiceBiomarkerMSAC outcomeYear
KRAS mutation testing for panitumumab KRAS mutation status supported 2013
RAS (KRAS and NRAS) mutation testing RAS (KRAS and NRAS) mutations supported 2014

Consumer voice

Mar 2024

The Medical Oncology Group of Australia (MOGA) expressed support for the cetuximab submission seeking the addition of the fortnightly dosing regimen. No other consumer comments were received.

The MOGA expressed support for the cetuximab submission seeking the addition of the fortnightly dosing regimen. Consumer comments · PSD
treatment burdenaccess barriers

Similar precedents

By decision profile

Regulatory · TGA

Label narrower than PBS population — PBAC restricts to RAS wild-type patients and specific treatment lines; TGA label includes all EGFR-expressing patients regardless of RAS status.