North of England Cancer Drugs Approval Group (NECDAG) Cumulative Table of Decisions August 2012

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1 Notes: This document is updated every 2 to 3 months; please check our website for latest version. This document does not all contain Interim Cancer Drugs Fund s, i.e. decisions made as part of setting up Interim cancer drug fund are not included, only new decision for CDF funding from April These can be found at:: This contains a record of all decisions made by NECDAG since May It must be viewed in conjunction with the Network list of approved cancer medicines and recent decisions by NICE. Section 2 of the document contains a summary of all NICE decisions implemented by NECDAG. Drug(s) Indication Date Estimated Cost Impact (NECN) Yttrium 90 microsphere (SIRT) APPROVED from the Cancer Drug Fund funding for 20 patients meeting the following criteria, HCC patients to allow transplant and CRC patients with liver predominant potentially operable metastases, who are having chemotherapy for metastatic disease. Audit to be carried out after 15 patients Rejected from standard NHS funding See CDF Funding Priority List (web link above) See indication Cetuximab (Erbitux ) (colorectal 3rd line Colorectal Cancer k-ras-wild type metastatic: THIRD line as a single agent or in combination with FOLFIRI / Irinotecan (Note single agent previously PCT funded) Rejected by NICE, prior NECDAG funding approval withdrawn See CDF Funding Priority List (web link above) Fulvestrant (Faslodex) Patients who are post-menopausal and have oestrogen reception positive advanced or metastatic breast cancer with : 1 relapsed on aromatase inhibitor (AI) 2 severe joint pains exacerbated by AI therapy. 3 swallowing and or compliance problems AND agreement from the Local Breast MDT that initiation of fulvestrant is the best treatment option available to the patient Rejected by NICE prior NECDAG funding approval withdrawn See CDF Funding Priority List (web link above) NECDAG Table of s August 2012 v2 Page 1 of 24 last Updated 25/07/2012

2 Drug(s) Indication Date Sorafenib (Nexavar) Unresectable Differentiated Thyroid Cancer refractory to iodine and Medullary Thyroid Cancer unsuitable for entry into Vandetanib Clinical Trial Rejected from standard NHS funding See CDF Funding Priority List (web link above) Denosumab (Xgeva) Selected patients with advanced breast or prostate cancer with bone metastases, Rejected from standard NHS funding See CDF Funding Priority List (web link above) Vemurafenib (Zelboraf) 1st line treatment of inoperable or metastatic BRAF V600 mutation +ve melanoma Rejected from standard NHS funding See CDF Funding Priority List (web link above) Ritixumab (mabthera ) Rituximab + CHOP as Induction Chemotherapy forr Mantle cell NHL and Rituximab as Maintenance Therapy ,250 For use in patients in Patients unsuitable for NORDIC chemotherapy Schedule. Note Not approved for use with FC chemotherapy regimen) Erlotinib (Tarceva) 1st line treatment advanced or metastatic non-small cell lung cancer (NSCLC) with EGFR activating mutations Cost Neutral There is a degree of uncertainty regarding average drug costs; what is apparent is that there will be a very low additional budget impact as erlotinib would be used instead of existing Gefitnib (Iressa) treatment. Eribulin (Halven) locally advanced or metastatic breast cancer who have progressed after at least 3 chemotherapeutic regimens Rejected from standard NHS funding See CDF Funding Priority List (web link above) NECDAG Table of s August 2012 v2 Page 2 of 24 last Updated 25/07/2012

3 Drug(s) Indication Date Bevacizumab* Avastin (Ovarian) In combination with carboplatin and paclitaxel for up to 6 cycles, then single agent ,084 The dosing schedule NECDAG agreed was the 7.5mg/kg IV three weekly dose from the ICON-7 Trial. Given until disease progression, unacceptable toxicity or a maximum of 12 months. This is administered with carboplatin and paclitaxel for 5-6 courses and then a further 12 course as monotherapy. (total doses=18). Abiraterone Castrate resistant metastatic prostate cancer previously treated with a docetaxel-containing regimen Rejected from standard NHS funding See CDF Funding Priority List (web link above) Bevacizumab* Avastin (Breast) Advanced/ metastatic breast cancer for triple negative patients with capecitabine Rejected from standard NHS funding See CDF Funding Priority List (web link above) Ipilumimab 2nd line treatment of Metastatic melanoma Rejected from standard NHS funding See CDF Funding Priority List (web link above) Imatinib (Glivec) Adjuvant treatment of adult patients with GIST Treatment at 400mg daily for 3 years ,320 year 1, 534,888 year 2 rising to 755,136 For patients only with a significant risk of relapse, NECDAG it likely that the Cost per ICER QALY for this indication lies in the region of 20-30k. Vinorelbine (Navelbine) and Capecitabine (Xeloda) Metastatic Breast Cancer Cost Neutral Combination instead of sequentially for selected patients where a higher chance of response than with the individual drugs important. NECDAG Table of s August 2012 v2 Page 3 of 24 last Updated 25/07/2012

4 Drug(s) Indication Date Weekly Carboplatin and paclitaxel Heavily pretreated platinum-resistant recurrent ovarian cancer, good performance status(0-1) Cost Neutral Weekly dose dense paclitaxel and carboplatin regime has been reported to have high response rate & tolerable toxicity. Cisplatin and Vinorelbine (chemoradiation) Non Small Cell Lung Cancer Cost Neutral Change to Concurrent Chemo with RTx as standard treatment to appropriately selected patients, instead of sequential treatment. FOLFIRINOX Oxaliplatin, Leucovorin, Irinotecan, 5FU Management of selected patients with inoperable pancreatic cancer ,500 First line for inoperable pancreatic cancer in patients with performance status 0-1. Gemcitabine and Capecitabine Management of advanced pancreatic cancer REJECTED 206,250 The committee was of the view that the clinical evidence was weak, with 3 RCT trials, two of which did not show any statistically significant benefit for the combination vs. gemcitabine. Degarelix (Firmagon) 1st line advanced hormone-dependent prostate cancer at with a PSA > 20ng/l Cost Neutral This expands a previous restricted approval (see decision below on Lenalidomide (Revlimid) for Myelodysplastic syndrome with the 5q minus cytogenetic abnormality & REJECTED 250,000 The committee and appeal (for CDF) as there was a lack of haematology expertise to advise the committee at original meeting. On appeal there were still safety concerns and lack of evidence. Cabazitaxel (Jevtana ) 2nd line treatment castrate resistant prostate cancer Rejected from standard NHS funding See CDF Funding Priority List (web link above) NECDAG Table of s August 2012 v2 Page 4 of 24 last Updated 25/07/2012

5 Drug(s) Indication Date Dexrazoxane (Savene TM ) Treatment of extravasation Agreed to add to NECN Guidance See comments Considered part of Tariff by NECN commissioners Dasatinib (Sprycel ) and Nilotinib (Tasigna ) 1st line Chronic Myeloid Leukaemia (CML) REJECTED See comments NECDAG S view is there is already an effective 1 st line treatment and these drugs as yet offer no long term survival advantage over imatinib. These agents are approved 2 nd line in NHS North East, first line approval would remove the option of 2 nd line treatment Sorafenib (Nexavar ) Thyroid Cancer REJECTED Currently unlicensed and a clinical trial was noted as being available. Vinflunine (Javlor ) Advanced Transitional Cell Carcinoma of the Urothelial Tract (TCCU) Sunitinib (sutent ) Metastatic/ unresectable well differentiated pnets pancreatic neuroendocrine tumour Rejected from standard NHS funding Rejected from standard NHS funding See CDF Funding Priority List (web link above) See CDF Funding Priority List (web link above) Bendamustine (Levact ) 1 st line treatment of chronic lymphocytic leukemia (Binet stage B or C) in patients for whom Fludarabine combination chemotherapy is not appropriate ,380 None Ritixumab (mabthera ) First-line maintenance in follicular non-hodgkin s lymphoma Year 1 712,913 rising to 1,425,827 year 2 onwards Following 1 st line chemotherapy, given as maintenance therapy every 8 weeks for 2 years (12 doses) NECDAG Table of s August 2012 v2 Page 5 of 24 last Updated 25/07/2012

6 Drug(s) Indication Date Ritixumab (mabthera ) Newly diagnosed mantle cell NHL in fit patients aged <60years old Maximum 98K None Lapatinib (Tyverb ) plus an Aromatase Inhibitor (AI) (HER2) positive postmenopausal women with hormone receptor positive (HR+) metastatic breast cancer Rejected None As not being implemented The committee concluded that Lapatinib+ AI did not meet the current NICE criteria for cost effectiveness. nab-paclitaxel (Abraxane) 'Paclitaxel albumin (Abraxane) is accepted for restricted use within its current license for metastatic breast cancer patients who cannot tolerate standard taxanes with restrictions Net cost of 73 to 147K NECDAG recognises that standard docetaxel and paclitaxel remain the first choice taxanes for metastatic breast cancer, however Abraxane will offer significant advantages for those patients who clinicians feel are unable to tolerate the taxanes treatment regimens or for patients that experience an adverse reaction to a standard taxane Faslodex (Fulvestrant ) solution for injections Post-menopausal and ER+ve, with Advanced/Metastatic Breast Cancer Patients: Update of decision of April 2009 with restrictions Additional expenditure of 150k. Previously approved , the licensed dose has now changed from 250mg monthly to 500mg monthly, with a 50% increase in costs. The new dose and costs were acceptable to NECDAG Ritixumab (mabthera ) Nodular lymphocytepredominant Hodgkin lymphoma (NLPHL) K to 293K per anum NECDAG concluded whilst there was no robust clinical evidence, e.g. phase III RCTs, there are technical and biological reasons to support its use for a limited number of patients rather than clinicians using Exceptional Circumstance NECDAG Table of s August 2012 v2 Page 6 of 24 last Updated 25/07/2012

7 Drug(s) Indication Date Traztusumab (herceptin ) with cisplatin and fluorouracil/capecitabine 1st line metastatic or locally advanced inoperable gastric cancers which over express HER-II (IHC +++ or IHC +++ FISH 12th May ,432 per anum NECDAG found the cost per QALY to be in the region of 52-66k per QALY gained. The treatment was thought likely to meet the NICE end of life criteria. NECDAG noted that trastuzumab is available for treatment of metastatic breast cancer with similar survival improvements and costs. Degarelix (Firmagon) 1 st line advanced hormone-dependent prostate cancer with: PSA > 50ng/l or urether obstruction or symptoms of spinal cord compression Cost neutral for restricted patients on the condition that the manufacturer either discounts or rebates the cost to be equivalent to the cost of gosarelin. Capecitabine + irinotecan (CAPIRI) Metastatic colorectal cancer Cost neutral As an alternative to FOLFIRI (Modified de Gramont + irinotecan). CAPIRI has comparable efficacy and tolerability to FOLFIRI, however, CAPIRI is more patient-friendly in that it does not require a central line and reduces visits to hospital. Cetuximab (Erbitux ) 3rd Line single agent in KRAS wild-type metastatic colorectal cancer patients ,884 to 489,158 The committee felt that the strong evidence of improved survival (4.7months) for 3rd line single agent combined with a PAS scheme to reduce costs (the same pas NICE approved for 1st line cetuximab) allowed the drug to be approved under the NICE end of life ruling. Gemcitabine Adjuvant treatment for pancreatic cancer Gateway Sub Group Max cost to NECN 187,000 per anum Trials confirm survival advantage for adjuvant Gem compared to observation in patients who had had their pancreatic cancer treated surgically. Gemcitabine and Cisplatin Palliative treatment for biliary tract cancers Gateway Sub Group Cost neutral, potentially cost saving This regimen would involve adding cisplatin to gemcitabine which is already approved in upper GI cancers or replacing existing ECX. NECDAG Table of s August 2012 v2 Page 7 of 24 last Updated 25/07/2012

8 Drug(s) Indication Date Capecitabine and streptozocin Neuroendocrine tumours (NET) Gateway Sub Group Cost neutral Strepotozocin is already in use in an alternative schedule at centres treating NET. The approval allows replacement of 5FU/ Folinic Acid with Capecitabine. Aprepitant (EMEND) and Palonosetron (Aloxi ) Chemotherapy induced nausea & vomiting (CINV) Gateway Sub Group Included in tariff Palonosetron as an option for prevention of chemotherapy induced nausea & vomiting (CINV) in selected patients receiving moderate (ME) or highly emetogenic (HE) chemotherapy. Aprepitant as an option for prevention CINV in selected patients receiving HE chemotherapy Rituximab in combination with Fludarabine & Cyclophosphamide For patients with CLL Binet stage B or C, as treatment of relapsed disease September ,600 NECDAG has previously approved the use of FCR as first line treatment of CLL.However, this additional approval allows access for those patients who are at a later stage of treatment. Lapatinib (Tyverb) Breast cancer September 09 Not None In comparison with trastuzumab after progression lapatinib could be cost effective, however, NICE does not recommend trastuzumab be continued beyond progression. In comparison with standard chemotherapy the QALY is above the limits set by NICE hence the committee were unable to approve Plerixafor (Mozobil ) Stem cell mobilisation in the management of patients failing first mobilisation with multiple myeloma & lymphoma September 09 78,128 to 117,192 The use of plerixafor appears to significantly improve the chance of successful stem cell transplant (Tx) in a small number of patients who fail conventional transplant conditioning regimens. Bevacizumab (Avastin ) Metastatic colorectal cancer patients with unresectable liver only metastases with mutated KRAS 1st July 2009 Rejected None As not being implemented. The committee concluded that the clinical evidence was not of the level of benefit normally required for acceptance into clinical practice and noted the suggestion that a randomised trial was needed to confirm benefit. NECDAG Table of s August 2012 v2 Page 8 of 24 last Updated 25/07/2012

9 Drug(s) Indication Date yttrium-90 radiolabelled ibritumomab tiuxetan (Zevalin ) Consolidation therapy after remission induction in previously untreated patients with follicular lymphoma Gateway Sub Group 10th June 2009 Rejected None As not being implemented. The committee did not feel there was currently sufficient clinical evidence to support use in the previously untreated setting, as patients locally would have received rituximab as part of their indication therapy. Deferasirox (Exjade ) Iron Chelation for patients with Myelodysplastic Syndrome (MDS) Gateway Sub Group 10th June 2009 with restrictions Net Cost to NECN = 10,000 The committee approved the recommendation to use defarasirox rather than less evidence based approaches such as transfusion of chelating agents immediately following transfusion. Cisplatin and Etoposide For induction concurrent Chemoradiotherapy To Superior Sulcus carcinomas of lung Gateway Sub Group 10th June 2009 Drug costs maximum 200 per patient. The committee felt that a 10% five year survival benefit off-set a very small financial cost. Bortezomib (Velcade ) First line therapy for multiple myeloma patients who have renal failure requiring haemodialysis or in whom use of melphalan is prohibited Gateway Sub Group 10th June 2009 Expected to be cost neutral The committee that any additional costs from re-sequencing the treatment would be offset by reducing dialysis costs. Ritixumab (CLL) with Fludarabine and Cyclophosphamide First Line treatment of Chronic Lymphocytic Leukaemia in combination with FC Chemotherapy. 29th April 2009 with restrictions Net Cost of adding Rituximab to FC (with VAT) 271,170 Review decision on publication of final NICE Guidance Azacitidine (Vidaza ) Myelodysplastic Syndrome (MDS) 29th April 2009 Rejected None As not being implemented. The committee concluded the health economic case resulted in a QALY greater than the normal NICE threshold. This treatment fits the NICE End of Life Treatment criteria, however, the committee were concerned that the economic uncertainties and higher than normally acceptable QALY would result in a negative opinion from NICE. NECDAG Table of s August 2012 v2 Page 9 of 24 last Updated 25/07/2012

10 Drug(s) Indication Date Bevacizumab (Avastin ) Metastatic Breast Cancer 29th April 2009 Rejected None As not being implemented. The committee were unable to approve at this time because the limited overall survival advantage, and limited evidence of a difference in utility between the control arm and treatment arms of the trial meant it impossible to develop a health economic model which could produce a QALY value under the normal limits approved by NICE. Faslodex (Fulvestrant ) solution for injections Post-menopausal and ER+ve, with Advanced/Metastatic Breast Cancer Patients: Gateway Sub Group 1st April 2009 with restrictions Net Cost to NECN = 62,688 to 83,584 Treatment to be administered in primary after administration of the first cycle in secondary care. Restricted to patients who/with: 1. Relapsed on AI therapy in advanced disease 2. Severe joint pains exacerbated by AI therapy. 3. Compliance issues Oral Topotecan (Hycamtin ) Relapsed Small Cell Lung Cancer (SCLC) in patients for whom re-treatment with 1st-line regime is not appropriate. 4th February 2009 Net Cost 55,008 for the Network. The committee concluded that oral topotecan is at least as effective as VAC with the added benefit of improved symptom control and significant benefits in terms of quality of life and ease of administration. Docetaxel (Taxotere ) with carboplatin Ovarian cancer: for patients that have demonstrated an allergic reaction to paclitaxel (CTC grade 3 or above hypersensitivity 4th February 2009 Net Cost to NECN = 91,863 to 137,794 The committee if the reported paclitaxel hypersensitivity reaction was an issue that could be resolved by switching from generic paclitaxel to the non-contract branded equivalent. The safest approach for patients was to switch to docetaxel. Pemetrexed (Altimta ) with Platinum First Line Non Small Cell Non Squamous Histology- Lung Cancer (2 nd line see comments) 3 rd December & 4 th February 2009 First line 341,334 for the Network. (2 nd line cost neutral with refund scheme) Replacement of 1 st line Gemcitabine +Cisplatin or Carboplatin with Pemetrexed+Cisplatin or Carboplatin for patients with Non-Squamous Histology (Large Cell and Adenocarcinoma) adds 2 months to median survival. 2nd line use allowed only for patients who started 1st line prior to to allow equity of access. NECDAG Table of s August 2012 v2 Page 10 of 24 last Updated 25/07/2012

11 Drug(s) Indication Date Lenalidomide (Revlimid ) Relapsed/ Refractory Multiple Myeloma 24 th September Rejected None as not being implemented. The committee were unable to approve at this time as the economic case had not been demonstrated, but noted that NICE was due to review the treatment. Lenalidomide is the most expensive cancer medicine on the market, it would cost an average of 48,268 per patient for 11 months treatment and potentially 2,461,668 for network. Sorafinib (Nexavar ) Treatment of hepatocellular cancer 24 th September Rejected None as not being implemented. The committee were unable to approve as the economic case had not been demonstrated. Docetaxel (Taxotere ) and Cyclophosphamide (TC) Adjuvant node positive Breast cancer unsuitable for anthracyline 24 th September 5,000 to 15,000 per PCT As an option for the adjuvant treatment of women with early operable node positive breast cancer (stages 1-3) who have a history of cardiac disease making them unsuitable for standard anthracycline based adjuvant chemotherapy MP-T (Thalidomide in combination with Melphalan and Prednisolone) First line therapy for multiple myeloma patients Gateway Sub Group 9 th September Cost Neutral Negligible impact as systems are already in place to provide Thalidomide on a Third Line therapeutic basis. EOX Epiribicin, oxaliplatin, capecitabine Inoperable oesophagogastric cancer. Gateway Sub Group 9 th September Max cost across NECN will be 126,053. To replace ECX and EcarboX in suitable patients. Dasatinib (Sprycel ) Chronic Myeloid Leukaemia with resistance or intolerance to prior therapy including imatinib 24 th September with restrictions See nilotinib costs Following nilotinib s approval dasatinib was accepted as an alternative for patients intolerant to nilotinib. Dasatinib must not be used after failure on nilotinib. (Clinicians have freedom to choose most appropriate agent nilotinib or dasatinib) NECDAG Table of s August 2012 v2 Page 11 of 24 last Updated 25/07/2012

12 Drug(s) Indication Date Nilotinib (Tasigna ) Patients with Imatinibresistant or intolerant Chronic Phase Chronic Myeloid Leukaemia (CML) 9 th July with restrictions 265,422 for the Network. Nilotinib will replace higher doses of imatinib in patients who are resistant to imatinib, and be used as an alternative treatment for patients unable to tolerate imatinib Cisplatin and 5FU: Neoadjuvant setting in head and neck cancer. Gateway Sub Group 18th June Cost neutral This treatment is currently offered after radiotherapy this is simply a switch in sequencing. TIP: (Paclitaxel, Ifosfamide Cisplatin) Second-line (post-bep) salvage chemotherapy for patients with metastatic germ cell cancer. Gateway Sub Group 18th June Cost neutral Accepted as standard practice. Thyrotropin Alpha (Thyrogen diagnostic tool for serum thyroglobulin testing in tracking patients with thyroid cancer. Gateway Sub Group 18th June Approve 232 per dose Has been available as standard practice some parts of Network but not others. Gateway agreed it is accepted as standard practice and should be available across network Irinotecan Advanced colorectal cancer 23 January Cost Neutral Addition of weekly single agent irinotecan as option for treatment of advanced colorectal cancer, for those patients not suitable for NICE approved 3 weekly regimen Topotecan (Hycamtin ) (in combination with cisplatin) Carcinoma of the cervix recurrent after radiotherapy and for patients with Stage IVB disease. 23 January with restrictions 37,500 for the Network. Restricted to patients who have been cisplatin free for a period of at least 12 months. Use without GCSF Support 2 nd line Sunitinib (Sutent ) for GIST Gastrointestinal Stromal Tumours (GIST) after Imatinib Failure 23 January 130,163 for the Network. using reduced costs from Sunitinib risk share scheme to achieve cost effectiveness. NECDAG Table of s August 2012 v2 Page 12 of 24 last Updated 25/07/2012

13 Drug(s) Indication Date 2 nd Line FOLFIRI (Irinotecan Modified DeGramont) Advanced colorectal cancer 7 November ,400 for the Network. FOLFIRI is approved as 2 nd line therapy following 1 st line treatment with FOLFOX. Erlotinib (Tarceva ) Non Small Cell Lung Cancer 2 nd Liner as an alternative to docetaxel (Taxotere) 7 November 2007 as an alternative to 2 nd line docetaxel (Taxotere). 4,931 per patient (125 days treatment) In theory implementation is cost neutral since patients who would have received docetaxel will receive erlotinib at equivalent price. The committee acknowledged the convenience of the oral dose form and favourable side effect profile may mean that patients eligible for docetaxel who will received erlotinib who would not have tolerated docetaxel. Cisplatin & Docetaxel (Taxotere ) Advanced Oesophago-gastric Cancer for patients unsuitable for ECX/ECF 7 November ,420 Restricted to patients unsuitable for standard therapy with ECF or ECX regimens due to potential toxicity with fluoropyrimidine based chemotherapy. Neulasta (pegfilgrastim) 6mg solution for injection Reduction in the duration of neutrophenia and the incidence of febrile neutropenia (FN) in chemotherapy patients 7 November 2007 Up to 502,634 (However potentially cost neutral dependant on current GCSF usage) Certain Trusts in NECN purchase Neulasta via a price deal with Amgen based on replacing existing GCSF usage with Neulasta (pegfilgrastim). NECN asked the manufacturers to provide the same offer of price deal to all Trusts in the Network. (Not for use in patients with the CML & MDS) Oral Vinorelbine (Navelbine ) A single agent or in combination for the treatment of advanced breast cancer 7 November ,000 Used for patients with stage 3 and 4 relapsing after or refractory or anthracycline containing regimen. Aprepitant (Emend ) Prevention of Chemo Induced Nausea & Vomiting in patients receiving high dose cisplatin & patients who fail standard antiemetic 23 July 2007 Clinical Approval* 1 cycle of treatment costs Typical cost per patient around 280. *To be funded by Trusts as commissioners view is costs for supportive care are covered within tariff individual costs per PCT or Trust have not been calculated NECDAG Table of s August 2012 v2 Page 13 of 24 last Updated 25/07/2012

14 Drug(s) Indication Date Ritixumab (Follicular Lymphoma) Relapsed/ refractory follicular lymphoma responding to induction chemotherapy with or without Rituximab. 23 July 2007 Year 1-268,514 Year 2-537,028 Further work ongoing defining the patient pathway for follicular lymphoma. Sunitinib (Sutent ) First line for Renal Cell Carcinoma 23 July ,600 per year + (a non-recurrent cost of 202,620*) *NE NHS Chief Executives agreed the small number of patients who have already received first line treatment with interferon prior to this decision may be able to receive Sunitinib if clinically appropriate. (Approx 12). This is not approval for 2nd line use but recognition that there are some patients who may benefit. Zevaline (Yttrium-90 labelled Ibritumomab tiuxetan) The treatment of adult patients with CD20+ follicular B-cell non- Hodgkin s lymphoma (NHL) resistant to/ relapsed after Rituximab. 7 March 2007 Rejected 10, per patient per year. None as not being implemented. Dasatinib (Sprycel ) for Chronic Myeloid Leukaemia Adults with chronic, accelerated or blast phase chronic myeloid leukaemia (CML) with resistance or intolerance to prior therapy including imatinib (Gilvec). 7 March 2007 Rejected 31,714 per patient per year. None as not being implemented. Reject upon review in March will be subject reviewed in September Bexarotene (Targretin ) Skin manifestations of advanced stage (CTCL) cutaneous T-cell lymphoma patients refractory to at least one systemic therapy 7 March 2007 with restrictions 90,000 per year maximum. Likely to be 45K per year as a number of patients already treated NECDAG Table of s August 2012 v2 Page 14 of 24 last Updated 25/07/2012

15 Drug(s) Indication Date Sorafenib (Nexavar ) and Sunitinib (Sutent ) Second line for Renal Cell Carcinoma 7 February 2007 Rejected None -not being implemented. No published cost effectiveness data was available Pegylated- Cytarabine (Depocyte ) Intrathecal treatment of lymphomatous meningitis 7 February ,275 Centre only treatment Oral Uftoral (tegafur/uracil) Advanced Colorectal Cancer 1 November ,500 for both Oral Uftoral & Folinic Acid. Previously NICE approved. Unable to estimate uptake, likely to be small and instead of existing treatment option. Temozolomide (Temodal ) Concomitant & adjuvant temozomide with radiotherapy at presentation malignant glioma (brain tumour) and good performance status 1 November ,960 per year. Subsequently NICE approved Docetaxel (Taxotere ) FEC-T Adjuvant use in patients with Node Positive Breast Cancer 1 November 2006 Drug costs per patient would be around 5.3K plus 3K for additional costs giving totals of 169,600 and 96,000 NICE approved NICE estimates that 32 patients per million population will be eligible for treatment with this regimen. Capecitabine GI Cancers (ECX regimen etc) 5 July 2006 Cost Neutral Delivery cost should be neutral and capacity from nursing and pharmacy time being freed would be able to be redeployed for delivery of NICE Adjuvant Colon Guidance. NECDAG Table of s August 2012 v2 Page 15 of 24 last Updated 25/07/2012

16 Drug(s) Indication Date Alemtuzumab (MabCampath ) Chronic Lymphocytic Leukaemia with disease less than 5 cm (Third Line) 5 July 2006 Approximately 15 patients per year costing 65,000 Erlotinib (Tarceva ) Non Small Cell Lung (Second or Third Line) 5 July 2006 Rejected The Committee noted that no published cost effectiveness data was available. An estimate Cost per Life Year Gained and QALY had been made. The Committee concluded that the economic case had not been demonstrated. SUPERCEDED by DECISION Oral Vinorelbine (Navelbine ) Non Small Cell Lung (First Line) NSCLC Equalising practice between CCA and NCN (previously approved in NCN) Cetuximab (Erbitux ) Colorectal cancer metastatic 3 May 2006 Rejected Rejected due to lack of clinical evidence of improvement in survival vs. standard treatment (best supportive care) and High cost per QALY. superceded by nice TA118 NECDAG Table of s August 2012 v2 Page 16 of 24 last Updated 25/07/2012

17 Section 2: NICE Implementation This section contains a summary of all positive NICE decisions discussed by NECDAG Drug(s) Indication Date of NICE Guidance Reference Abiraterone (Zytiga) Prostate cancer (metastatic, castration resistant) - (following cytotoxic therapy) June 2012 APPROVED TA258 Currently funded by CDF. Will be funded from CDF until 27 September 2012, (90 day post NICE decision) at which time funding will switch to NHS commissioners (PCT/CCGs) Erlotinib (Tarceva) Lung cancer (non small cell, EGFR-TK mutation positive) - 1st line June 2012 APPROVED TA258 Previously by NECDAG March 2012 Nilotinib (Tasigna ) Nilotinib and standarddose imatinib for the firstline treatment of chronic myeloid leukaemia ( April 2012 APPROVED TA251 Nilotinib has been added to approval for 1st line therapy as part of review of NICE guidance TA70 due to manufacturer discounting drug to match price of imatinib. However this has not yet been implemented due to availability of Nilotinib in an ongoing clinical trial Nilotinib (Tasigna ) 2nd line therapy after standard dose imatinib in CML chronic myeloid leukaemia Jan 2012 APPROVED TA241 NICE did not recommend high-dose imatinib or Dasatinib for people with Philadelphiachromosome-positive chronic myeloid leukaemia in the chronic, accelerated or blast-crisis phase that has got worse after treatment with standarddose imatinib Rituximab (MabThera ) Follicular lymphoma Jan 2012 APPROVED TA243 Rituximab for the first-line treatment of stage III- IV follicular lymphoma is recommended in combination with certain chemotherapies as a possible treatment for people with stage III IV follicular lymphoma ( (review of NICE TA110) NECDAG Table of s August 2012 v2 Page 17 of 24 last Updated 25/07/2012

18 Drug(s) Indication Date of NICE Guidance Reference Mifamurtide (Mepact) Osteosarcoma Oct 2011 APPROVED TA235 Mifamurtide is made available at a reduced cost to the NHS under the patient access scheme. bortezomib and thalidomide Multiple myeloma (first line) - July 2011 APPROVED TA228 NECN Haematology NSSG asked to produce treatment algorithm for MM Rituximab (MabThera ) Follicular non-hodgkins lymphoma (maintenance treatment following response to first-line chemotherapy) June 2011 APPROVED TA226 Previously approved by NECDAG Jan 2011 Bendamustine (Levact ) Chronic lymphocytic leukaemia February 2011 APPROVED TA216 Previously approved by NECDAG Jan 2011 Pazopanib Renal cell carcinoma (first line metastatic) February 2011 APPROVED TA215 NICE approval is on the basis of the average cost of treatment being the same as sunitinib, with similar clinical efficacy. However if average treatment duration is generally shorter then the cost of pazopanib is higher than sunitinib, as both drugs have PASs which operate in different ways. Current audit data in the North East suggest the duration of treatment is shorter than seen in trials. Trusts to assure themselves Traztusumab (herceptin ) HER2-positive metastatic gastric cancer November 2010 APPROVED TA208 Previously approved by NECDAG May 2010 NECDAG Table of s August 2012 v2 Page 18 of 24 last Updated 25/07/2012

19 Drug(s) Indication Date of NICE Guidance Reference Gefitinib (Iressa) Advanced/ metastatic non-small-cell lung cancer 1 st line August 2010 APPROVED TA191 Implemented in October 2010 after consideration of issues surrounding EGFR testing and the PAS scheme for prescribing the drug. Pemetrexed (Alimita) Maintenance treatment of non-squamous nonsmall-cell lung cancer June 2010 APPROVED TA190 NICE does not allow use of maintenance therapy for patients who have received 1 st line pemetrexed. It is anticipated that the majority of non-squamous histology patients in NECN will have already received pemetrexed as first line combination, therefore use as maintenance treatment in NECN will be limited Sorafenib (Nexavar) 1st line treatement of advanced and metastatic Hepatocellular carcinoma May 2010 Not recommended TA189 Previously reviewed and rejected by NECDAG. Trabectedin (Yondelis) Advanced soft tissue sarcoma February 2010 APPROVED TA186 Estimated very small numbers of patients who would be treated at cancer centres. Topotecan Relapsed small cell lung cancer November 2009 APPROVED TA184 NICE recommend use of topotecan is restrcited to patients in whom re-treatment with the previous treatment is not appropriate and there is a medical reason why they cannot take (CAV) cyclophosphamide, doxorubicin and vincristine. NECDAG Previously approved for use as an alternative to CAV due to decreased toxicity. Clinicians are advised to use clinical judgement on patients suitability to receive CAV. NECDAG Table of s August 2012 v2 Page 19 of 24 last Updated 25/07/2012

20 Drug(s) Indication Date of NICE Guidance Reference Pemetrexed first-line treatment of non-small-cell lung cancer September 2009 APPROVED TA181 Previously by NECDAG ( Dec ) Sunitinib gastrointestinal stromal tumours (GIST) September 2009 APPROVED TA179 Previously by NECDAG ( Jan ) Cetuximab (Erbitux ) Combination with 5-FU, folinic acid & oxaliplatin (FOLFOX) for first line colorectal cancer with potentially operable liver metastases August 2009 TA176 The manufacturer rebates 16% of the amount of cetuximab used on a per patient basis by means of a Patient Access Scheme (PAS). Lenalidomide (Revlimid ) Relapsed/ Refractory Multiple Myeloma June 2009 TA171 NICE allowed use for patients who have received at least one prior therapy and where a Risk Share Scheme is in place to provide free drug for patients who continue on treatment after 2 years. Sunitinib (Sutent ) First line for Renal Cell Carcinoma March 2009 for patients suitable for interferon with performance status 0 or 1. TA169 Already implemented in NECN. Erlotinib (Tarceva ) Non Small Cell Lung Cancer November as an alternative to 2 nd line docetaxel (Taxotere). TA162 NICE state. Erlotinib should be used only when the manufacturer provides the drug at the same overall treatment cost as docetaxel. In practice NICE have accepted a scheme similar to one approved by NECDAG in Nov Trusts should not a slight increase in costs (from 1,182 to 1,394 per month) as NICE did not obtain as favourable a discount as NECDAG NECDAG Table of s August 2012 v2 Page 20 of 24 last Updated 25/07/2012

21 Drug(s) Indication Date of NICE Guidance Reference Cetuximab (Erbitux ) (in combination with radiotherapy) Treatment of Head and Neck Cancer June Restricted approval for locally advanced squamous cell head and neck cancer with Karnofsky PS 90% not suitable for platinum chemo TA145 The possible patient group is very restricted. Most patients would be suitable for platinum based chemotherapy in combination with radiotherapy and there is currently no evidence of superiority of cetuximab for this patient population. Cetuximab (Erbitux ) Metastatic colorectal cancer following failure of oxaliplatin-containing chemotherapy June Not recommended (Non-submission) TA150 NICE was unable to recommend the use in the NHS because no evidence submission was received from the manufacturer. Carmustine implants (Gliadel ) treatment of recurrent glioblastoma multiforme June Not recommended (Non-submission) TA149 NICE was unable to recommend the use in the NHS because no evidence submission was received from the manufacturer Bevacizumab (Avastin ) non-small-cell lung cancer June Not recommended (Non-submission) TA148 NICE was unable to recommend the use in the NHS because no evidence submission was received from the manufacturer Bevacizumab (Avastin ) in combination with paclitaxel first-line treatment of metastatic breast cancer June Not recommended (Non-submission) TA147 NICE was unable to recommend the use in the NHS because no evidence submission was received from the manufacturer. NECDAG Table of s August 2012 v2 Page 21 of 24 last Updated 25/07/2012

22 Drug(s) Indication Date of NICE Guidance Reference Erythropoietin analogues; epoetin alfa & beta (Eprex & NeoRecormon) and darbepoetin alfa (Aranesp) Treatment of symptomatic anaemia in adults who are receiving chemotherapy May Not recommended for routine use. (Small use in ovarian/ patients unable to receive transfusions) TA142 There was some use of Erythropoietin analogues currently in NECN, Trusts should disinvest as appropriate. The NCN had previously produced guidance on the use of Erythropoietin analogues, this has now been officially withdrawn. Rituximab (MabThera ) Relapsed or refractory stage III or IV follicular non-hodgkin's lymphoma February Recommended for 1st line in combination, maintenance and last line monotherapy TA137 Rituximab is an option in combination with chemotherapy to induce remission or alone as maintenance therapy during remission. Rituximab monotherapy is an option for relapsed or refractory disease when all alternative treatment options have been exhausted. Pemetrexed (Altimta ) Mesothelioma January for PS 0 or 1 patients TA135 NICE guidance matches prior approval by NE Cancer Networks Bortezomib (Velcade ) Monotherapy for relapsed multiple myeloma October 2007 for patients who relapse for the first time after having one treatment, TA129 following adoption of VRS scheme. Patients tested for response after not more than four cycles. If non responders then stopped and NHS gets refunded. Pemetrexed (Altimta ) 2nd line locally advanced or metastatic non-smallcell lung cancer August 2007 Not recommended TA124 Carmustine (Gliadel ) Implants and temozolomide (Temodal ) Glioma (newly diagnosed and high grade) June 2007 Recommended with restrictions TA121 Temozolomide for newly diagnosed glioblastoma multiforme with PS 0 or 1 Carmustine implants for newly diagnosed high-grade glioma only if 90% or more of their tumour has been removed, only at specialist centres/ James Cook and Newcastle. NECDAG Table of s August 2012 v2 Page 22 of 24 last Updated 25/07/2012

23 Drug(s) Indication Date of NICE Guidance Reference Fludarabine Phosphate (Fludara ) first-line treatment of chronic lymphocytic leukaemia February 2007 Not recommended TA119 The manufacturer s NICE submission included fludarabine monotherapy and fludarabine plus cyclophosphamide compared with chlorambucil based on the results of the CLL4 trial. However the combination regimen is unlicensed in the UK therefore NICE declined to comment on it. NICE only commented on the single agent Fludarabine which is not as effective as combination. Gemcitabine and Paclitaxel Metastatic breast cancer January 2007 Recommended with restrictions TA116 Recommended as where two other treatments could also be used as alternatives. Bevacizumab (Avastin ) & cetuximab (Erbitux ) Colorectal cancer metastatic January 2007 Not recommended TA118 Bevacizumab with 5-fluorouracil plus folinic acid, with or without irinotecan not recommended for first line. Cetuximab with irinotecan not recommended for patients who had previous treatment that also included irinotecan. Anastrozole (Arimidex), exemestane (Aromasin) and letrozole (Femara) Hormonal therapies for the adjuvant treatment of early oestrogenreceptor-+ve breast cancer Nov 2006 Recommended TA112 NICE recommend all three drugs and state there is insufficient evidence to conclude that any one aromatase inhibitor or treatment strategy is more clinically effective than another NECN has produced guidance on use of adjuvant AI s. NECDAG Table of s August 2012 v2 Page 23 of 24 last Updated 25/07/2012

24 Drug(s) Indication Date of NICE Guidance Reference Rituximab (MabThera ) R- CHOP Stage III or IV follicular lymphoma Sep 2006 Recommended TA110 R CHOP regimen, ritxumab plus cyclophosphamide, vincristine and prednisolone. Docetaxel (Taxotere ) Adjuvant use in patients with Node Positive Breast Cancer Sep 2006 Recommended TA109 NICE recommend use of licensed FAC regimen NECDAG have and approved alternative FEC-T regimen Paclitaxel Adjuvant use in patients with Node Positive Breast Cancer Sep 2006 Not recommended TA108 Not found to be cost effective, docetaxel approved as adjuvant taxanes. Trastuzumab (Herceptin ) Docetaxel (Taxotere ) Adjuvant use in patients with HER2 Positive Breast Cancer hormone refractory prostate cancer Aug 2006 Recommended TA107 Previously implemented in NECN area. June 2006 Recommended TA101 Capecitabine and oxaliplatin adjuvant treatment of stage III (Dukes' C) colon cancer April 2006 Recommended TA100 Capecitabine on its own and oxaliplatin together with 5-fluorouracil and folinic acid are recommended as possible adjuvant treatments after surgery for stage III (Dukes C) colon cancer, when used in the following ways: NECDAG Table of s August 2012 v2 Page 24 of 24 last Updated 25/07/2012