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 Essen%al Medicines List Secretariat Essen%al 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 l The difficult job of an Expert Committee l 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 l Cancer drugs: a large comprehensive review (29 applications) l New highly effective HCV drugs (new direct antiviral, single agents and combinations, IFN free regimens) l TB drugs (4+1) l New oral anticoagulants l a tight Agenda 5

6 EML 2015: 16 new cancer medicines included l 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. l 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) ü An antibody blocking HER-2, which is over-expressed in 20 to 25% of women with breast cancer. ü Rapidly approved by regulatory agencies for the treatment of women with MBC. ü Open debate and great attention by the media Approvation for MBC and EBC 8

9 Trastuzumab (Herceptin) Population: Interventions: Comparator: Outcom es: Type of studies: Women with HER2 positive metastatic or operable early breast cancer, of any age, menopausal status or hormone receptor status. 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(%) year trastuzumab 19.4% Not effective 80 Observation 6.6% Necessary & effective year Events DFS HR 95% CI p value 74% Not necessary Effectiveness on disease relapse , 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 15 Deaths

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

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 =

19 SoF death 19

20 SoF DFS 20

21 SoF harm 21

22 EML comprehensive cancer review: methodology l The cancer WG discussed thresholds for clinical benefits and acknowledged their importance but did not endorse an explicit threshold l 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 l Some medicines included in EML are cost effective AND unaffordable: this will require actions to increase access to these essential medicines 22

23 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 23

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25 EML 2015: Le Monde (13 May 2015): change of paradigm 25

26 EM Model List Team l Nicola Magrini l Jeanne-Marie Scott l Bernadette Cappello l Lorenzo Moja l Gilles Forte l Kees De Joncheere 26