This is the text extract for Proposal to widen access to gemcitabine.; Closing Date: Closed; Contact: Jackie Evans, browse documents here.

---

15 December 2010

Proposal to widen access to gemcitabine

PHARMAC is seeking feedback on a proposal to widen funded access to the Pharmaceutical Cancer Treatment gemcitabine hydrochloride from 1 March 2011 to include funding for the treatment of patients with:   locally advanced or metastatic cholangiocarcinoma; and macroscopically resected pancreatic cancer.

Feedback sought PHARMAC welcomes feedback on this proposal. To provide feedback, please submit it in writing by 5 pm Wednesday, 12 January 2011 to: Jackie Evans Therapeutic Group Manager PHARMAC Email: jackie.evans@pharmac.govt.nz Fax: 04 460 4995 Post PO Box 10 254, Wellington 6143

All feedback received before the closing date will be considered by PHARMAC’s Board (or Chief Executive acting under delegated authority) prior to making a decision on this proposal.

Details of the proposal From 1 March 2011, the Special Authority criteria applying to the funding of gemcitabine hydrochloride (inj 1 g, inj 200 mg and inj 1 mg for ECP) would be amended as follows (changes in bold and strikethrough):

Gemcitabine – PCT only – Specialist - Special Authority for Subsidy Initial application — (Hodgkin’s Disease) only from a relevant specialist or medical practitioner on the recommendation of a relevant specialist. Approvals valid for 12 months for applications meeting the following criteria: All of the following: 1 The patient has Hodgkin’s Disease*; and 2 Any of the following: 2.1 Disease has failed to respond to second-line salvage chemotherapy treatment; or 2.2 Disease has relapsed following transplant; or 2.3 The patient is unsuitable for, or intolerant to, second-line salvage chemotherapy or high dose chemotherapy and transplant; and 3 Gemcitabine to be given for a maximum of 6 treatment cycles. Initial application — (T-Cell Lymphoma) only from a relevant specialist or medical practitioner on the recommendation of a relevant specialist. Approvals valid for 12 months for applications meeting the following criteria: Both: 1 The patient has T-cell Lymphoma*; and 2 Gemcitabine to be given for a maximum of 6 treatment cycles.

A392526 Page 1 of 5

---

Initial application — (Cholangiocarcinoma) only from a relevant specialist or medical practitioner on the recommendation of a relevant specialist. Approvals valid for 12 months for applications meeting the following criteria: Both: 1 The patient has locally advanced or metastatic, cholangiocarcinoma*; and 2 Gemcitabine to be given for a maximum of 8 treatment cycles.

Initial application — (Pancreatic Cancer) only from a relevant specialist or medical practitioner on the recommendation of a relevant specialist. Approvals valid for 12 months for applications meeting the following criteria: Either 1 All of the following; 1.1 The patient has macroscopically resected (R0) pancreatic carcinoma*; and 1.2 Adjuvant gemcitabine to be administered for a maximum of 6 cycles; or 2. Both: 2.1 The patient has advanced pancreatic carcinoma; and 2.2 The patient is gemcitabine treatment naïve. Renewal - (Pancreatic Cancer) only from a relevant specialist or medical practitioner on the recommendation of a relevant specialist. Approvals valid for 12 months for applications meeting the following criteria: All of the following: 1 The patient has received gemcitabine for advanced pancreatic carcinoma; and 2 The patient has not received gemcitabine for adjuvant treatment pancreatic carcinoma; and 3 The patient requires continued therapy. Initial application — (Other indications) only from a relevant specialist or medical practitioner on the recommendation of a relevant specialist. Approvals valid for 12 months for applications meeting the following criteria: Any of the following: 1 1 The patient has non small cell lung carcinoma (stage IIIa, or above); or 2 The patient has advanced malignant mesothelioma; or 3 The patient has advanced pancreatic carcinoma; or 4 3The patient has ovarian, fallopian tube* or primary peritoneal carcinoma*; or 5 4 The patient has advanced transitional cell carcinoma of the urothelial tract (locally advanced or metastatic). Renewal — (Other indications) only from a relevant specialist or medical practitioner on the recommendation of a relevant specialist. Approvals valid for 12 months for applications meeting the following criteria: Either: 1 The patient requires continued therapy; or 2 The tumour has relapsed and requires re-treatment. Note: Indications marked with a * are Unapproved Indications.

Background Gemcitabine hydrochloride is a DHB hospital administered Pharmaceutical Cancer Treatment (PCT), therefore the proposal would have resource implications for DHB hospitals

A392526T10-523

Page 2 of 5

---

associated with administration of the treatment (see sections below for details of resource implications). In 2008 and 2009, PHARMAC received 2 separate applications from the Gastrointestinal Cancer Special Interest Group of the New Zealand Association of Cancer Specialists (GISIG) requesting the funding of gemcitabine for the treatment of patients with locally advanced, or metastatic, cholangiocarcinoma and the adjuvant treatment of patients with macroscopically resected pancreatic cancer. Each proposal is discussed separately below. Cholangiocarcinoma: The term ‘cholangiocarcinoma’ encompasses epithelial tumours of the hepatobiliary tree, including tumours of bile ducts, ampulla of vater and gallbladder. The majority of patients, with cholangiocarcinoma present with inoperable disease, and in such patients expected survival is generally less than 1 year. In this patient group, the goal of chemotherapy treatment is palliative; to improve quality of life and extend survival. There is currently no standard treatment for these patients in New Zealand, the most common treatment for these patients is currently combination chemotherapy with epirubicin, cisplatin and a fluoropyrimidine (infusional 5-flurouracil or oral capecitabine) (ECF/X). However, the evidence for this treatment is limited. Evidence from clinical trials indicates that combination treatment with combination gemcitabine and cisplatin improves median survival by approximately 3.5 months compared with gemcitabine alone. Whilst there is no evidence directly comparing gemcitabine with fluoropyrimidine based regimens (such as ECF/X) a retrospective pooled meta-analysis of a large number of trials indicates that there is a trend towards higher response rates and better tumour control rates in studies using gemcitabine-based combination regimens compared with fluoropyrimidine-based regimens. PTAC considered an application to fund gemcitabine for locally advanced/metastatic cholangiocarcinoma at its February 2010 meeting and recommended it be funded only if cost neutral to the health sector. The Cancer Treatments Subcommittee of PTAC (CaTSoP) considered the application at its April 2010 meeting and recommended that gemcitabine be funded in this setting with a high priority. This recommendation was reviewed and accepted by PTAC at its August 2010 meeting. Minutes available on our website here: www.pharmac.govt.nz/PTAC/PTACminutes and www.pharmac.govt.nz/PTAC/PTACSCMinutes. It is anticipated that this part of the proposal would result in approximately 120 additional patients accessing funded gemcitabine annually. Each patient would require 8 cycles of treatment, with each 3 week cycle consisting of one 30 minute infusion on days 1 and 8, a total of 16 x 30 minute infusions per patient. Therefore, the total additional DHB hospital service requirement nationally is expected to be up to 1,920 x 30 minute infusions per year.. It should be noted that some of this additional service requirement would be offset by a reduction in current services associated with current treatment options and the retreatment of patients with relapsed disease. However, it is expected that up to half of the patients treated with gemcitabine and cisplatin would go on to receive additional treatments after gemcitabine for relapsed disease, most likely ECF/X or capecitabine alone. Gemcitabine is not registered by Medsafe for the treatment of patients with cholangiocarcinoma, therefore, in this setting it would need to be prescribed and used in accordance with Section 25 of the Medicines Act.

A392526T10-523

Page 3 of 5

---

Resected Pancreatic Cancer: PHARMAC previously consulted on a proposal to fund adjuvant gemcitabine for resected pancreatic cancer on 29 July 2009, however, due to new data becoming available that proposal was not progressed. This new data has now been evaluated by PTAC and CaTSoP and we are once again proposing to fund gemcitabine for these patients. The most common type of pancreatic cancer, adenocarcinoma, arises from the exocrine glands and is one of the most aggressive types of cancer. Pancreatic cancer in the early stages has few, non-specific, symptoms, therefore, by the time it is diagnosed in most patients it will have spread to distant sites in the body, consequently survival in patients with pancreatic cancer is generally poor, with estimates of 5-year survival less than 5%. Prominent risk factors for pancreatic cancer include smoking and a history of chronic pancreatitis. The rate of pancreatic cancer is approximately 50-100% higher in Maori compared with non-Maori. Pancreatic cancer is relatively resistant to chemotherapy treatment, and the only potentially curative treatment is surgery. Evidence demonstrates that in patients with resected pancreatic cancer, gemcitabine improves disease free survival by approximately 6 months compared with best supportive care. However, gemcitabine offers no efficacy benefit compared with the so called “Mayo” fluorouracil (5-FU) based chemotherapy regimen, although gemcitabine was associated with fewer toxicities. Fluorouracil (5-FU) based chemotherapy is the current standard adjuvant treatment for resectable pancreatic cancer in New Zealand. Although there is good evidence that the ‘Mayo’ 5FU chemotherapy regimen is equivalent to gemcitabine in patients with resected pancreatic cancer (discussed above) this regimen is seldom used in New Zealand, instead oncologists here either use a weekly 5FU chemotherapy regimen, as it is considered to be less toxic and more convenient to deliver that the Mayo regimen, or best supportive care. However, unlike in the colorectal cancer setting, there is no evidence supporting the equivalence of the Mayo and weekly 5FU regimens in pancreatic cancer. PTAC considered the application at its February and November 2009 meetings and recommended the application be declined. CaTSoP considered the application at its February 2009 and August 2010 meetings and recommended that adjuvant gemcitabine be funded for patients with resected pancreatic cancer with a high priority. Following review of CaTSoPs recommendation at its November 2010 meeting, PTAC recommended that gemcitabine be funded with a low priority. Minutes available on our website here: www.pharmac.govt.nz/PTAC/PTACminutes and www.pharmac.govt.nz/PTAC/PTACSCMinutes. It is anticipated that this part of the proposal would result in approximately 80 additional patients accessing funded gemcitabine annually. Each patient would require 6 cycles of treatment, with each cycle consisting of one 30 minute infusion each week for 3 weeks, a total of 18 x 30 minute infusions per patient. Therefore, the total additional DHB hospital service requirement nationally is expected to be up to 1,440 x 30 minute infusions per year. It should be noted that some of this additional service requirement would be offset by a reduction in current services associated with current treatment options and the retreatment of patients with relapsed disease. However, it is expected that the majority of patients treated with gemcitabine would go on to receive additional treatments for relapsed disease.

A392526T10-523

Page 4 of 5

---

Gemcitabine is currently funded for the treatment of patients with advanced (metastatic) pancreatic cancer, under this proposal the funding of gemcitabine for these patients would be amended such that if patients had received funded gemcitabine in the adjuvant setting they would not be funded for further gemcitabine treatment in the metastatic setting, these patients would have the option of receiving 5FU based chemotherapy or best supportive care. Gemcitabine is not registered by Medsafe for the adjuvant treatment of patients with pancreatic cancer, therefore, in this setting it would need to be prescribed and used in accordance with Section 25 of the Medicines Act.

A392526T10-523

Page 5 of 5