Each year about 7100 new cases are diagnosed annually in the UK and it causes about 7250 deaths. It is usually diagnosed late and only about 10-20% of patients are eligible for resection. Patients with unresectable locally advanced disease (Stage 3) have a median survival of 6-11 months, and those with metastatic disease have a median survival of 2- 6 months. In 2001, NICE recommended that gemcitabine may be used as a first line treatment of people with advanced or metastatic pancreatic cancer if they have a Karnofsky performance score of 50 or more. This guidance will not be reviewed again unless new evidence becomes available.

Although gemcitabine is only licensed for use as a single agent in the treatment of advanced pancreatic cancer, erlotinib is licensed for use in combination with gemcitabine in patients with metastatic disease. Capecitabine is not licensed for use in this cancer. In a fully published meta-analysis that compared outcomes in patients treated with gemcitabine-based combination therapy and gemcitabine alone, data from 22 RCTs (involving a total of 5473 randomised patients) showed that combination treatment is associated with the following outcomes a 4% absolute difference in overall survival rates at 6 months in favour of combination therapy with a 95% confidence interval extending from 1% to 6% (this equates to a number needed to treat (NNT) of 25 (14 to 100) to produce one additional survivor at 6 months. a 3% absolute difference in overall survival rates at 12 months in favour of combination therapy with a 95% confidence interval extending from 1% to 5% (this equates to an NNT of 33 (20 to 100) to produce one additional survivor at 12 months.

There is one fully published Phase III study comparing outcomes in patients randomised to receive gemcitabine plus erlotinib or gemcitabine alone. It was shown that the median survival was 6.24 months in the combination arm compared with 5.91 months in the gemcitabine arm – an absolute difference of about 10 days. The combination was also associated with 6% absolute increase in 1 year survival rates (23% vs. 17%) meaning that for every 16 patients that receive the combination one additional patient will be alive at 12 months. There is one unpublished Phase III study showing that gemcitabine plus capecitabine is associated with a statistically significant increase in survival compared to gemcitabine alone. In this study the median survival was 7.4 months in the combination arm compared with 6 months in the gemcitabine arm - an absolute difference of about 42 days. The combination was associated with a 7% absolute increase in 1 year survival rates (26% vs. 19%) meaning that for every 14 patients that receive the combination one additional patient will be alive at 12 months.

There is also a fully published Phase III study assessing the gemcitabine/ capecitabine combination (although capecitabine was dosed less intensively) which reports similar results but in this case the results did not reach statistical significance.

The incremental cost differential for the erlotinib-based combination regimen is £6179 per patient (£10,606 vs £4427 excluding VAT) and therefore assuming there are between 1.5 and 3 cases per 100,000 population eligible for chemotherapy a switch to this regimen from gemcitabine monotherapy would probably increase drug costs by between £9300 and £18600 per year. The incremental cost differential for the capecitabine-based regimen is £1170 per patient (£5597 vs £4427 excluding VAT) and therefore to switch to this regimen from gemcitabine monotherapy would probably increase costs by between £1750 and £3500 per 100,000 population per year. The Scottish Medicines Consortium recently rejected the use of gemcitabine plus erlotinib in NHS Scotland on the basis that the market authorisation holder did not submit a case to the Consortium for consideration.