Cetuximab, solution for I.V. infusion, 100 mg in 20 mL, 100 mg in 50 mL and 500 mg in 100 mL, Erbitux®
Public summary document for Cetuximab, solution for I.V. infusion, 100 mg in 20 mL, 100 mg in 50 mL and 500 mg in 100 mL, Erbitux®
Page last updated: 30 October 2009
Public Summary Document
Product: Cetuximab, solution for I.V. infusion,
100 mg in 20 mL, 100 mg in 50 mL and 500 mg in 100 mL,
Erbitux®
Sponsor: Merck Serono Australia Pty Ltd
Date of PBAC Consideration: July 2009
1. Purpose of Application
The submission requested an Authority required listing (and
inclusion in the Chemotherapy Pharmaceuticals Access Program
(CPAP)) of cetuximab for the treatment of patients with metastatic
colorectal cancer following failure of irinotecan and failure of or
intolerance to oxaliplatin.
2. Background
This was the sixth application for listing of cetuximab for the
treatment of metastatic colorectal cancer (mCRC).
For further details of these considerations please refer to the
Public Summary Documents from the November 2005, November 2008 and
March 2009 PBAC meetings.
Cetuximab is currently listed on the PBS for use in squamous cell
cancer of the head and neck.
3. Registration Status
Cetuximab solution for I.V. infusion 2 mg /mL was TGA registered on 4 February 2005. Additional strengths (50 mg/ 10 mL, 100 mg/20 mL, 250 mg/mL and 500 mg/100 mL) were TGA registered on 25 September 2007. All strengths are indicated for:
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 as a single agent;
Treatment of patients with locally advanced squamous cell cancer of the head and neck, in combination with radiation therapy.
4. Listing Requested and PBAC’s View
Authority Required
Initial and Continuing
PBS-subsidised treatment of patients with metastatic colorectal cancer with a WHO
performance status of 2 or less, in combination with irinotecan, where:
Patients have received and failed 5-fluorouracil or capecitabine, received and failed an irinotecan based therapy and received and failed or are unsuitable for an oxaliplatin based therapy.
(b) There is evidence that the patient has K-Ras wild type in the tumour material.
For PBAC’s view, see Recommendation and Reasons.
5. Clinical Place for the Proposed Therapy
Cetuximab provides a treatment option for patients with metastatic
colorectal cancer who have failed the current standard
chemotherapeutic options.
6. Comparator:
The resubmission nominated best supportive care (BSC) as the
comparator. This was as previously accepted by the PBAC.
7. Clinical Trials
The submission presented no new data compared to the November 2008
submission.
8. Results of Trials
For the key results, see November 2008 PSD.
9. Clinical Claim
Cetuximab plus best supportive care (BSC) is superior in terms of
overall survival compared to BSC.
Cetuximab with irinotecan combination therapy is superior in terms
of overall survival compared to cetuximab monotherapy.
10. Economic Analysis
The re-submission presented the various sensitivity analyses for
the additional survival benefit from combination therapy with
cetuximab and irinotecan (C+I), in increments of one week, over
cetuximab monotherapy, including12 weeks and 17 weeks of irinotecan
therapy.
11. Estimated PBS Usage and Financial Implications
No further estimates of PBS usage or financial implications were
provided.
12. Recommendation and Reasons
The PBAC recognised that there was a clinical need for cetuximab
for the treatment of colorectal cancer.
The PBAC noted that no new clinical data were presented in this
submission but additional comments on biomarker identification and
revised economic evaluation sensitivity analyses were
presented.
The PBAC noted that the revised sensitivity analyses consider the
impact of additional survival derived from combination treatment of
irinotecan and cetuximab over cetuximab alone on the ICER in 1 week
increments and consider the addition of both 12 week and 17 weeks
of irinotecan to cetuximab monotherapy. The PBAC noted that the
incremental cost of combination treatment of both 12 weeks and 17
weeks was in the range of $15,000 - $45,000. The PBAC considered
that an additional survival benefit of at least 19 weeks would be
needed to offset the additional cost of irinotecan with estimated
ICERs in the ranges $15,000 - $75,000/QALY for both 12 weeks and 17
weeks.
This compared with a trial based ICER in the same range for
cetuximab monotherapy based on the CO-17 Study with a possible
survival advantage over BSC of 4.7 months. The PBAC concluded that
the magnitude of the benefit of cetuximab to offset the cost of
adding irinotecan to the treatment regimen was uncertain and that
the cost of cetuximab and/or irinotecan would need to be
decreased.
The PBAC therefore rejected the submission for cetuximab on the
basis of high and uncertain cost-effectiveness.
Recommendation
Reject
13. Context for Decision
The PBAC helps decide whether and, if so, how medicines should be
subsidised in Australia. It considers submissions in this context.
A PBAC decision not to recommend listing or not to recommend
changing a listing does not represent a final PBAC view about the
merits of the medicine. A company can resubmit to the PBAC or seek
independent review of the PBAC decision.
14. Sponsor’s Comment
Merck Serono Australia notes that the PBAC recognised the clinical
need for cetuximab in the treatment of colorectal cancer, however
is disappointed with the decision made at this time.
