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The National Institute for Health and Clinical Excellence (NICE) have announced their decision not to recommend the use of Tarceva (erlotinib) for the treatment of locally-advanced or metastatic non-small-cell lung cancer (NSCLC) in the National Health Service (NHS) in England and Wales.

NICE’s Final Appraisal Determination (FAD) on Tarceva last week concluded that the drug “could not be considered a cost-effective use of NHS resources” when compared with either docetaxel or best supportive care. People currently receiving Tarceva “should have the option to continue therapy until they and their clinicians consider it appropriate to stop.” The Appraisal Committee that assessed Tarceva, also indicated that it awaits the results of ongoing trials comparing the drug with docetaxel, and recommends further research into subgroups for whom Tarceva “may provide greater benefit.”

This is an interesting perspective, given the US approach of screening patients who are EGFR-positive with K-Ras mutations who would be suitable for Tarceva therapy. Taking a break from chemotherapy may also prolong survival across multiple lines of therapy. Docetaxel is well known for its severe myelosuppressive effects that cause cancer patients to feel exhausted and beaten up. Tarceva, a small molecule targeted therapy has been shown to be superior to placebo in efficacy, survival and quality of life, so the decision is somewhat surprising clinically.

To put it in context, chemotherapy is only somewhat effective for patients with advanced NSCLC, although there is some evidence for a benefit in terms of survival and symptom relief. Response times to treatment are brief, and the median time to cancer progression is three to five months. In patients who initially received platinum-based chemotherapy for NSCLC, docetaxel offers the chance to improve survival for those with disease progression. Data suggests, however, that third-line chemotherapy is similar to supportive care in terms of survival, and the response rates to such therapy are bleak.

A randomized, placebo-controlled, double-blind trial was recently conducted to determine whether the EGFR inhibitor erlotinib prolongs survival in non–small-cell lung cancer after the failure of first-line or second-line chemotherapy. It clearly demonstrated that erlotinib prolonged survival.

Eligible patients had stage IIIB or IV NSCLC, with performance status of between 0 and 3, and had undergone one or two prior rounds of chemotherapy. In a 2:1 ratio, 731 patients were randomized to receive either 150 mg of oral erlotinib daily or placebo, and they were stratified by center, performance status, response to prior chemotherapy, number of prior rounds of chemotherapy, and prior platinum-based therapy. Median age was 61.4 years, 49% had undergone two prior rounds of chemotherapy, and 93% had received platinum-based chemotherapy. Response rate was 8.9% with erlotinib and less than 1% with placebo (P < .001), with respective median durations of response being 7.9 and 3.7 months.

After adjustment for stratification categories, progression-free survival was 2.2 months with erlotinib and 1.8 months with placebo (hazard ratio [HR], 0.61; P < .001). Overall survival was 6.7 months with erlotinib and 4.7 months with placebo (HR, 0.70; P < .001). Only 5% of patients discontinued erlotinib because of toxic side effects.

The positive clinical data has been available in the public domain for a while now. This appears to be a financial decision rather than a clinical one. Given that the drug budget is a very small part of the overall NHS budget, one wonders why they don’t attack the overinflated administrative staff budget with the same verve and vigour that they do with the relatively much smaller drug budgets.