Proposal to widen funded access to temozolomide for treatment of neuroendocrine tumours and high grade gliomas

Medicines Consultation Closed

As part of PHARMAC’s 2015/16 annual Invitation to Tender, PHARMAC is proposing to widen access to fully-funded temozolomide for the treatment of neuroendocrine tumours and high grade gliomas.

A decision has not been made on the presentations in the tender so the brand names, pricing and timing for these changes, if they were to be implemented, is still to be determined; however, PHARMAC is seeking your feedback on the proposed new investment and funding criteria.

In summary, PHARMAC is seeking feedback on a proposal to amend the Special Authority criteria applying to temozolomide to include:

  • treatment beyond 6 cycles for high grade gliomas – glioblastoma multiforme or anaplastic astrocytoma.
  • the treatment of metastatic or unresectable neuroendocrine tumours;

Details of the proposed changes and background information can be found below and on the following pages.

Feedback sought

PHARMAC welcomes feedback on this proposal. To provide feedback, please submit it in writing by Wednesday, 25 May 2016 to:

Danae Staples-Moon
Therapeutic Group Manager
PHARMAC
PO Box 10254
Wellington 6143

Email: danae.staples-moon@pharmac.govt.nz

Fax: 04 460 4995

All feedback received before the closing date will be considered by PHARMAC’s Board (or its delegate) prior to making a decision on this proposal.

Feedback we receive is subject to the Official Information Act 1982 (OIA) and we will consider any request to have information withheld in accordance with our obligations under the OIA. Anyone providing feedback, whether on their own account or on behalf of an organisation, and whether in a personal or professional capacity, should be aware that the content of their feedback and their identity may need to be disclosed in response to an OIA request.

We are not able to treat any part of your feedback as confidential unless you specifically request that we do, and then only to the extent permissible under the OIA and other relevant laws and requirements. If you would like us to withhold any commercially sensitive, confidential proprietary, or personal information included in your submission, please clearly state this in your submission and identify the relevant sections of your submission that you would like it withheld. PHARMAC will give due consideration to any such request.

Details of the proposal

PHARMAC is seeking feedback on a proposal to make the changes outlined below in conjunction with the awarding of temozolomide tender bids as part of PHARMAC’s 2015/16 annual Invitation to Tender. The proposed changes would widen funded access to temozolomide for the treatment of metastatic or unresectable neuroendocrine tumours and treatment beyond 6 cycles for high grade gliomas (glioblastoma multiforme or anaplastic astrocytoma).

The proposed changes to the funding criteria are as follows:

  • The Special Authority criteria applying to temozolomide cap 5 mg, 20 mg, 100 mg and 250 mg would be amended as follows in Section B of the Pharmaceutical Schedule at a date to be determined (additions in bold, deletions in strikethrough):
  • Initial application - (high grade gliomas) only from a relevant specialist. Approvals valid for 10 12 months for applications meeting the following criteria:

All of the following:

  1. Either:
    1. Patient has newly diagnosed glioblastoma multiforme; or
    2. Patient has newly diagnosed anaplastic astrocytoma*; and
  2. Temozolomide is to be (or has been) given concomitantly with radiotherapy; and
  3. Following concomitant treatment adjuvant temozolomide is to be used in 5 day treatment cycles for a maximum of six cycles of 5 days treatment at a maximum dose of 200 mg/m2 per day.

Renewal application - (high grade gliomas) only from a relevant specialist. Approvals valid for 12 months for applications meeting the following criteria:

Either:

  1. Both:
    1. Patient has glioblastoma multiforme; and
    2. The treatment remains appropriate and the patient is benefitting from treatment; or
  2. All of the following
    1. Patient has anaplastic astrocytoma*; and
    2. The treatment remains appropriate and the patient is benefitting from treatment; and
    3. Adjuvant temozolomide is to be used for a maximum of 24 months.

Initial application - (neuroendocrine tumours) only from a relevant specialist. Approvals valid for 9 months for applications meeting the following criteria:

All of the following:

  1. Patient has been diagnosed with metastatic or unresectable well-differentiated neuroendocrine tumour*; and
  2. Temozolomide is to be given in combination with capecitabine; and
  3. Temozolomide is to be used in 28 day treatment cycles for a maximum of 5 days treatment per cycle at a maximum dose of 200 mg/m2 per day; and
  4. Temozolomide to be discontinued at disease progression.

Renewal application - (neuroendocrine tumours) only from a relevant specialist. Approvals valid for 6 months for applications meeting the following criteria:

Both:

  1. No evidence of disease progression; and
  2. The treatment remains appropriate and the patient is benefitting from treatment.

Notes: Indication marked with a * is an Unapproved Indication. Temozolomide is not subsidised for the treatment of relapsed glioblastoma multiforme. Reapplications will not be approved. Studies of temozolomide show that its benefit is predominantly in those patients with a good performance status (WHO grade 0 or 1 or Karnofsky score >80), and in patients who have had at least a partial resection of the tumour.

  • The HML restrictions for temozolomide would be amended in the same way.

Background

In PHARMAC’s 2015/16 annual Invitation to Tender, bids were sought for the supply of a number of medicines including temozolomide. As the amendment to the current listing would be implemented through the tender, the brands to be listed, the pricing and subsidy, and the dates of listing are still to be confirmed.

Temozolomide is an oral chemotherapeutic agent that is currently funded subject to Special Authority and HML restrictions for a maximum of 6 cycles as a first-line treatment for newly diagnosed high grade gliomas – glioblastoma multiforme and anaplastic astrocytoma.

Temozolomide is approved by Medsafe for the treatment of patients with newly diagnosed glioblastoma multiforme concomitantly with radiotherapy and then as adjuvant treatment, and for patients with recurrent high grade glioma, such as glioblastoma multiforme or anaplastic astrocytoma. It is also indicated for first line treatment for patients with advanced metastatic malignant melanoma.

High grade gliomas

Approximately 260 patients are diagnosed with primary brain cancer each year in New Zealand, approximately 80% of which are high grade gliomas. Of these, approximately 20% are anaplastic astrocytomas (grade III) and 80% are glioblastoma multiforme (grade IV).

The Pharmacology and Therapeutics Advisory Committee (PTAC) and the Cancer Treatments Subcommittee of PTAC (CaTSoP) have considered the funding of temozolomide for the treatment of high grade gliomas beyond 6 cycles in August 2014 and March 2014, respectively. The proposed criteria are in line with the advice received, which can be found on PHARMAC’s website at:

https://connect.pharmac.govt.nz/apptracker/s/global-search/temozolomide(external link)

We note that temozolomide is not registered by Medsafe for the treatment of patients with newly diagnosed anaplastic astrocytoma; therefore, in this setting it would need to be prescribed and used in accordance with section 25 of the Medicines Act 1981.

Neuroendocrine tumours

Neuroendocrine tumours (NETs) is the umbrella term for a group of unusual, often slow-growing cancers. These tumours develop from secretory cells which are found throughout the body and which are particularly concentrated in the gastrointestinal system, lung, pancreas, ovary and testes. These secretory cells are referred to as the diffuse endocrine system to separate them from the discrete endocrine organs such as pituitary, thyroid, parathyroid and adrenal glands. The term neuroendocrine implies that these cells have received some nervous connections (neuro-) and the cells have the ability to secrete hormones (endocrine).

Since 2013 PHARMAC has received a large number of Named Patient Pharmaceutical Assessment (NPPA) funding applications for temozolomide for patients with neuroendocrine tumours.

PTAC and CaTSoP have reviewed the funding of temozolomide for NETs on a number of occasions, most recently by CaTSoP at its April 2016 meeting. While the minute of this meeting is not yet finalised, the Subcommittee recommended that temozolomide be funded for patients with unresectable, well-differentiated NETs with a medium priority noting that this could include patients with NETS of low, intermediate and high grade.

The proposed SA criteria are in line with the advice received. The minutes of PTAC and CaTSoP’s discussions will be made available on the PHARMAC website at the following link as soon as they are finalised: PTAC

We estimate that approximately 50-60 patients per year with well-differentiated NETs would be eligible for funded treatment with temozolomide under the proposed access criteria.

We note that temozolomide is not registered by Medsafe for the treatment of patients with NETs; therefore, in this setting it would need to be prescribed and used in accordance with section 25 of the Medicines Act 1981.