July 2009 PBAC Outcomes - Subsequent Decisions not to Recommend

DRUG AND FORM	TGA INDICATION	CURRENT PBS LISTING	LISTING REQUESTED BY SPONSOR	PBAC OUTCOME AND COMMENTS
CETUXIMAB, solution for I.V. infusion 100 mg in 20 mL, 100 mg in 50 mL, and 500 mg in 100mL, Erbitux®     Merck Serono Australia Pty Ltd   Minor submission	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;   In combination with radiation therapy, for the treatment of patients with locally advanced squamous cell cancer of the head and neck.	Authority Required Initial treatment of stage III, IVa or IVb squamous cell cancer of the larynx, oropharynx or hypopharynx for the week prior to radiotherapy, where cisplatin is contraindicated according to the TGA-approved Product information; Initial treatment of stage III, IVa or IVb squamous cell cancer of the larynx, oropharynx or hypopharynx, in combination with radiotherapy, where cisplatin is not tolerated.   Authority Required Continuing treatment of stage III, IVa or IVb squamous cell cancer of the larynx, oropharynx or hypopharynx, in combination with radiotherapy, where cisplatin is either contraindicated or not tolerated.		The PBAC rejected the submission on the basis of high and uncertain cost-effectiveness.
			Authority required listing for third-line treatment of patients with K-Ras wild type metastatic colorectal cancer in combination with irinotecan.
			Comparator: Best supportive care (BSC).	Accepted (as previously).
			Clinical Claim: Cetuximab plus best supportive care 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.	Not accepted. No new clinical data were presented. The PBAC considered the magnitude of the treatment effect (overall survival) for combination therapy with cetuximab and irinotecan to be uncertain. The PBAC had previously considered the extent of survival benefit for cetuximab over BSC is uncertain as it relies on post-hoc analysis and extrapolation.
			Economic Claim: Cost effective	Not accepted. The ICER remains both high and uncertain. 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.
			Sponsor Comments:	The sponsor disagrees with the decision and is considering its position regarding any future course of action.
IVABRADINE HYDROCHLORIDE, film coated tablets, 5 mg and 7.5 mg, Coralan® Servier Laboratories (Australia) Pty Ltd   Major submission	Treatment of chronic stable angina due to atherosclerotic coronary artery disease in patients with normal sinus rhythm who are unable to tolerate or have a contraindication to the use of beta blockers.	Not currently listed.		The PBAC rejected the submission, deciding that it had no basis upon which to recommend the listing of ivabradine as the application did not provide evidence to directly or indirectly address the restriction requested.
			Authority required (Streamlined) listing for the treatment of chronic stable angina due to atherosclerotic coronary artery disease in a patient with a left ventricular ejection fraction of 40% or less and a resting heart rate of 70 bpm or greater, and who is receiving a beta blocker or is unable to tolerate or has a contraindication to a beta blocker.	The PBAC noted that in post submission comments the sponsor had indicated it considered the place of ivabradine was in the treatment of angina refractory to all other angina treatment.
			Comparator: Placebo	Not accepted for the requested listing. Currently listed second-line anti-anginal agents were considered more appropriate comparators.
			Clinical Claim: In treating stable angina to reduce symptoms and improve exercise tolerance in patients who also have left ventricular dysfunction and a resting heart rate of 70bpm or greater, ivabradine confers prognostic benefit when compared to placebo.	Not accepted. The PBAC considered the submission did not provide evidence to address the requested restriction, noting the submission sought to rely on a sub-group analysis which was of a subgroup of a post hoc subgroup.
			Economic Claim: Cost-effectiveness	Not accepted. The uncertainties in the clinical data mean that the cost-effectiveness analysis presented is inadequately supported.
			Sponsor Comments:	Servier is committed to ivabradine being available for some patients with stable angina and will work with the PBAC to achieve listing.