Erlotinib Maintenance in NSCLC Refused in the UK

Zosia Chustecka

June 29, 2011

June 29, 2011 — The National Institute for Health and Clinical Excellence (NICE) in the United Kingdom has upheld its original decision to refuse erlotinib (Tarceva, Roche) maintenance treatment for locally advanced or metastatic nonsmall-cell lung cancer (NSCLC). In an unusual move, executives from the institute have explained why in a special report published online June 29 in the Lancet Oncology.

The NICE decision means that erlotinib maintenance therapy for NSCLC will not be funded by the National Health Service (NHS) for patients in England and Wales. The drug remains approved for this indication, so patients could receive this treatment, but only by paying for it privately.

Erlotinib is also indicated for second-line treatment in lung cancer patients who have failed at least 1 previous chemotherapy regimen. Clinical trial data support its use as a first-line therapy in patients with an EGFR mutation, but this indication has not been approved as yet.

Not Cost Effective

The refusal to cover maintenance therapy is controversial. The initial decision, made in July 2010, was followed by a flurry of media reports about life-extending therapy being denied to patients. It was also followed by an appeal from the manufacturer, with an offer of a patient-access scheme, which would provide the drug at a discount to the NHS.

These strategies were unsuccessful, however, and the final ruling was negative. Perhaps because of the controversy, NICE now explains how the committee arrived at its decision.

The indication was not allowed on the basis of a lack of cost effectiveness and the number of patients affected, NICE executives explain.

The key evidence for the appraisal comes from the SATURN trial, in which erlotinib was compared with placebo in patients with advanced or metastatic NSCLC whose disease had not progressed after 4 cycles of platinum-based first-line chemotherapy. The trial involved 889 patients, of whom 487 (55%) had stable disease after first-line chemotherapy.

That trial showed a statistically significant improvement in progression-free survival in the erlotinib group, compared with the placebo group (12.1 vs 11.3 weeks; hazard ratio [HR], 0.68; 95% confidence interval [CI], 0.56 to 0.83; P < .0001). There was also a statistically significant improvement in mean overall survival (11.9 vs 9.6 months; HR, 0.72; 95% CI, 0.59 to 0.89; P = .0019).

The NICE executives point out that very few British patients participated in the SATURN trial, and that a high proportion of the trial participants had better prognostic factors than those seen in clinical practice in the Untied Kingdom, which could overestimate the efficacy of erlotinib. The results from this trial therefore have "limited generalizability to UK patients," the committee concludes.

In addition, the NICE committee points out that the size of the cumulative population eligible for treatment with erlotinib is "not small."

Economic models based on the SATURN results were used to calculate cost effectiveness. The manufacturer calculated that, compared with best supportive care, the incremental cost-effectiveness ratio for erlotinib maintenance worked out to ₤47,743 per quality-adjusted life year (QALY) gained for patients with stable disease. The NICE committee arrived at a figure of ₤59,336, and concluded that this figure "was the most plausible."

Both calculations are much higher than the upper limit of ₤30,000 per QALY that NICE uses as a cut-off in its appraisals.

Lancet Oncol. Published online June 29, 2011. Abstract