1. Use of Pemetrexed in Mesothelioma Citizens Council – November 2008

2. The Task Provide Guidance to the NHS on the use of pemetrexed in for people with malignant pleural mesothelioma Note that, in a nutshell, Pemetrexed confers about 3 months survival at an additional cost of £8000 plus the cost of managing greater toxicities

3. Pleural Mesothelioma Cancer of lining of lung – pleura

4. Pleural Mesothelioma 99% linked to asbestos exposure Can occur a long time after exposure: Age at presentation usually 60-80 yrs; Rising incidence: now 2000 patients/year Shortness of breath, chest pain, malaise, appetite loss, weight loss, sweats Almost always lethal over 6-18 months Prognostic factors: performance status [need to explain], stage [again may need to explain, age

5. Treatment Surgery rarely possible Active symptom control very important Chemotherapy: no standard treatment. In UK Vinorelbine or MVP (mitomycin, vinblastine, cisplatin) often used, but only on the basis of non-RCT evidence

6. The Evidence for Pemetrexed Randomised Controlled Trial of Cis+Pem vs Cisplatin alone Median Overall Survival Months CisplatinPemetrexed + Cisplatin All10.0 (n=163) 13.3 (n=168) HR 0.75 p=0.05 Those with Advanced disease 8.4 (n=122) 13.2 (n=125) HR 0.63 p=0.003 % alive at 1 year: 38(Cis) 50(Pem-Cis)p=0.02

7. Cis vs Cis+Pem Toxicity and QoL ToxicityCis %of people Cis+pem % of people Low White Blood cells 226 Nausea 612 Vomiting 410 Diarrhoea 04 Sores mouth/lips04 Quality of Life: Reported in abstract only Scores for global QOL, pain, dyspnoea and fatigue all significantly increased by week 15 in cis+pem arm QOL scores began to diverge by week 9

8. ICER for Cis+Pem (and if 100mg vial of pem available) Group [needs explaining] ICER £ per QALYMean overall survival change (months) FS60,56112.3 to 15.3 FS + AD49,05110.0 to 13.6 FS + PS 0/150,35713.0 to 16.5 FS + AD + PS 0/137,64410.3 to 15.5

9. The Main Arguments – for (1) (1)Innovative drug (2)Now used elsewhere in Europe and the USA (3)Trials without including pemetrexed now unlikely/unethical (4)The only licensed treatment (MVP and vinorelbine are used off license) and in any case cisplatin is a good model for these treatments (5)The best ICER is plausible as many (if not most) patients even with advanced disease are of good performance status

10. The Main Arguments – for Pem – Cis (2) (6) Rare disease (7)Time limited disease peak (the cohort of patients are now > 60) (8)Disadvantaged patients (those exposed to asbestos were usually asbestos factory workers and their families) (9) Societal responsibility for an industrial disease

11. The Main Arguments – Against (1)Clinical evidence is limited to one trial (2)The comparator in the trial is not standard UK practice (and the manufacturer was not persuaded to enter Pemetrexed into a trial of the other comparators – MS01) – a trial is needed (3)The Pem Cis regime is moderately toxic (more so than comparators) (4)All analyses, even those searching for sub-groups show Pem-Cis to be not cost-effective by normal rules ie well above £20,000 - £30,000 per QALY. And the only sub-group at less than £40,000 was a slightly artificial one of high performance status patients

12. Report Back Working in groups Try to come up with an agreed answer/ majority Did you all agree? What problems did you face?