Proposing Trastuzumab as an Essential Medicine to Treat Cancer: Insight on Methodologies, Processes and Outcomes. Lorenzo Moja

Transcription

1 Proposing Trastuzumab as an Essential Medicine to Treat Cancer: Insight on Methodologies, Processes and Outcomes Lorenzo Moja Essential Medicines List Secretariat Essential Medicines and Health Products Department Who is asking for a name: a window to understand the drugs of the future (R.Balocco) Contrast in Pharmacology 2.0 Turin, May, 2015

2 Outline The difficult job of an Expert Committee How to balance desirable and undesirable effects of medicines - cancer 2

3 WHO EML May,

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5 EML 2015: 77 applications and a few big challenges Cancer drugs: a large comprehensive review (29 applications) New highly effective HCV drugs (new direct antiviral, single agents and combinations, IFN free regimens) TB drugs (4+1) New oral anticoagulants a tight Agenda 5

6 EML 2015: 16 new cancer medicines included Some of these medicines produce relevant survival benefits for cancers with high incidence, such as trastuzumab for breast cancer, explained Dr Kees De Joncheere, WHO Director of Essential Medicines. Other treatment regimens for rare cancers such as leukemia and lymphoma, which can cure up to 90% of patients, were added to set a global standard. Kees De Joncheere, Director Essential Medicines Department, WHO 6

7 EML Cancer medicines update

8 Trastuzumab (Herceptin) An antibody blocking HER-2, which is over-expressed in 20 to 25% of women with breast cancer. Rapidly approved by regulatory agencies for the treatment of women with MBC. Open debate and great attention by the media Approvation for MBC and EBC 8

9 Trastuzumab (Herceptin) Population: Women with HER2 positive metastatic or operable early breast cancer, of any age, menopausal status or hormone receptor status. Interventions: Comparator: Outcomes: Type of studies: alone, following or in combination with chemotherapy. The same chemotherapy regimen or placebo. Primary: overall survival, progression free survival Randomised controlled clinical trials. 9

10 Trastuzumab in early breast cancer Disease-free survival (censored) - Median FU 2 yrs Patients(%) Observation 1 year trastuzumab 19.4% Not effective 6.6% Necessary & effective 60 74% Not necessary Effectiveness on disease relapse 40 3-year Events DFS HR 95% CI p value , 0.78 < Months from randomisation No at risk Conte, Oncologia, Modena 10

11 Explanations of EML decisions Assumed control group risk (without the intervention) is based on median control group risks reported in the included studies, or on epidemiological data from country registers. 11

12 Explanations of EML decisions Baseline (control group) risk: low risk 100 per 1000 High risk: 500 per 1000 Most important outcomes for someone making a decision. These include potential benefits and harms. 12

13 Explanations of EML decisions Corresponding treatment (trastuzumab) group risk. It is the risk of an outcome occurring in the group receiving the intervention (i.e. anticancer medicine). 13

14 Explanations of EML decisions The relative effect is derived by dividing the two risks, with the intervention risk being divided by the control risk: = Usually the absolute effect is different for groups that are at high and low risk, whereas the relative effect often is the same. 14

15 Explanations of EML decisions Trastuzumab absolute effect 50/100 Without Trastuzumab Deaths 15

16 Explanations of EML decisions Trastuzumab absolute effect 50/100 37/100 = 13 13% absolute difference With Trastuzumab Deaths Deaths avoided 16

17 Explanations of EML decisions With Trastuzumab Deaths Deaths avoided $ $ $ $ $ $ 17

18 Explanations of EML decisions With Trastuzumab Deaths Deaths avoided $ $ $ $ $ $ $ $ $ $ $ $ $ $ $ $ $ $ $ $ $ $ $ $ $ $ $ $ $ $ $ $ $ $ $ $ $ $ $ $ $ $ $ $ $ $ $ $ $ $ $ $ $ $ $ $ $ $ $ $ $ $ $ $ $ $ $ $ $ $ $ $ $ $ $ $ $ $ $ $ $ $ $ $ $ $ $ $ $ $ $ $ $ $ $ $ $ $ Without trastuzumab 1 year treatment costs about With trastuzumab 1 year treatment costs about All cohort NNT = 7 = $ $ 18

19 SoF death 19

20 SoF DFS 20

21 SoF harm 21

22 Metastatic breast cancer Add-on and alternatives to backbone therapy Backbone therapy Capecetabine 87 Vinorelbine 195 Aromatase inhibitors 37 Trastuzumab 73 Taxanes 17 CMF 37 Anthracyclines 47 Absolute Lives prolonged per 1000 patients Over 100 Essential Medicines Up to 75 Up to 100 Bevacizumab T-DM1 88 Pertuzumab 109 Up to 25 Up to 50 Very Limited or No Survival Benefit Potential Essential Medicines 22

23 Syndromic approach Decisions focused on diseases/treatment outcomes not individual medicines Two primary axes considered Burden of disease Clinical net benefit from systemic therapies 23

24 EML cancer update 2015: an overview Discussed as showing a large benefit: to be considered at next EC The application did not present the evidence supporting their use as second line agents: to be evaluated again at next EC 24

25 Application for DLBCL (diffuse large B cell lymphoma) Substantial chance for cure with medicines alone in a moderate-incidence disease CHOP can cure about 55% of patients Adding rituximab increases cure rates from 55% to 70% 25

26 Cancers Breast Colorectal Lung Prostate Haematology Additions aromatase inhibitors capacetabine leoprorelin trastuzumab vinorelbine capecitabine irinotecan oxapliplatin (FOLFOX- XELOX-FOLFIRI) cisplatin gemcitabine hormonal (bicalutamide, buserelin, goserelin,) ATRA (APML) bendamustine fludarabine imatinib rituximab Not proposed pertuzumab TDM-1 bevacizumab cetuximab abiraterone enzalutamide Proposed and rejected gemcitabine erlotinib gefitinb arsenic trioxide dasatanib nilotinib Worthing applications biphosphonatesp ertuzumab TDM-1 bevacizumab cetuximab afatinib crizotinib erlotinb gefitinb abiraterone enzalutamide dasatanib nilotinib ibrutinib 26

27 Accessibility 27 Cherny et al., Ann. of Onc. 2016

28 Impact India: Our List of Essential Medicines Expanded to 376. Drugs for Cancer, HIV/AIDS & More Get Affordable. The new list, which is effective immediately, is in line with WHO s 2015 list of essential drugs. GSK fils and enforces patents - IP protection - only in countries with advanced economic. Any GSK medicines on the WHO s list of essential medicines will not be patented in Least Developed Countries and Low Income Countries. Recommends to embrace new ways to pay for innovation and to increase access to health technologies. Current system relies on high drug prices to incentivize innovation, reducing access. De-linkage of cost of R&D from the prices of drugs. Innovation and access are combined. 28

29 FAILURE Cancer package in LMICs: tobacco control, palliative care, vaccination against viruses that cause cervical and liver cancer, diagnosis and treatment of breast and cervical cancer, and treatment of selected childhood cancers. Full implementation would cost an additional $20 billion per year, or 3% of total public spending on health in LMICs. The World Bank argues that this cost should be feasible in most countries. Failure because of absence of international coordination in oncology. Neither WHO nor the UICC have the resources to play this part effectively. 29

30 EM Model List Team Nicola Magrini Jeanne-Marie Scott Bernadette Cappello Lorenzo Moja Gilles Forte Kees De Joncheere 30

31 EML comprehensive cancer review: methodology The cancer WG discussed thresholds for clinical benefits and acknowledged their importance but did not endorse an explicit threshold The EC discussed the application and the importance of magnitude of benefit as the main criterion to include a medicines in EML but was out of its mandate to define a threshold for clinical benefit Some medicines included in EML are cost effective AND unaffordable: this will require actions to increase access to these essential medicines 31

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33 EML 2015: Le Monde (13 May 2015): change of paradigm 33

34 Selection criteria Guiding principle: A limited range of carefully selected essential medicines leads to better health care, better medicines management, and lower costs Definition: Essential medicines are those that satisfy the priority health care needs of the population Selection based on disease prevalence, evidence on efficacy and safety, and comparative cost-effectiveness (when alternatives are available) Price per se is not a selection criterion Feasibility is a factor that receives attention 34

35 EML cancer review st List 208 Medicines; 6 (<5%) cancer / 208 medicines st review cancer medicines; 14 cancer medicines nd and 3th reviews; 22 cancer medicines th review WHO-UICC; 16 medicines added / 22 requested 46 (> 10%) cancer / 409 medicines Broader perspective: medicines for palliation, and care of cancer symptoms and internal medicine related conditions: 100+ (25%+) medicines 35