Use of Pemetrexed in Mesothelioma

Citizen’s Council – November 2008

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

Pleural Mesothelioma Cancer of lining of lung – pleura

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

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

The Evidence for Pemetrexed Randomised Controlled Trial of Cis+Pem

vs Cisplatin alone

Median Overall Survival

Months

Cisplatin Pemetrexed +

Cisplatin

All 10.0

(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

Cis vs Cis+Pem Toxicity and QoL

Toxicity Cis

%of people

Cis+pem

% of people

Low White Blood cells 2 26

Nausea 6 12

Vomiting 4 10

Diarrhoea 0 4

Sores mouth/lips 0 4

Quality of Life: Reported in abstract onlyScores for global QOL, pain, dyspnoea and fatigue all significantly increased by week 15 in cis+pem armQOL scores began to diverge by week 9

ICER for Cis+Pem(and if 100mg vial of pem available)

Group

[needs explaining]

ICER £ per QALY Mean overall survival change

(months)

FS 60,561 12.3 to 15.3

FS + AD 49,051 10.0 to 13.6

FS + PS 0/1 50,357 13.0 to 16.5

FS + AD + PS 0/1 37,644 10.3 to 15.5

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”

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

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

Report Back

Working in groups• Try to come up with an agreed answer/

majority• Did you all agree?• What problems did you face?