NICE comes back with different views on Tarceva and Iressa for NSCLC

UK health costs watch dog the National Institute for Health and Care Excellence (NICE) is consulting again on its review of existing guidance on the use of Swiss drug major Roche’s (ROG: SIX) Tarceva (erlotinib) and Anglo-Swedish pharma firm AstraZeneca’s (LSE: AZN) Iressa (gefitinib)for treating non-small-cell lung cancer (NSCLC) that has progressed after prior chemotherapy.

A further set of updated draft guidance has been published, following a previous consultation. The new draft guidance provisionally recommends erlotinib as a treatment option for people with NSCLC that has progressed after prior chemotherapy in specific circumstances – but does not recommend gefitinib.

Both erlotinib and gefitinib are targeted therapies known as EGFR-TK inhibitors, they work by blocking the signal pathways helping to slow the growth and spread of tumors.

Existing NICE guidance recommends erlotinib with a patient access scheme as an alternative to docetaxel as a ‘second-line’ treatment after prior chemotherapy, however it is not recommended in people for whom docetaxel is unsuitable (NICE technology appraisal guidance 162). NICE was unable to make a recommendation on gefitinib for second-line treatment because no evidence submission was received from the manufacturer (NICE technology appraisal guidance 175).

Changes in clinical practice

Clinical practice has changed since the original guidance on erlotinib and gefitinib was published; people with NSCLC have their tumor tested for EGFR-TK mutation status at diagnosis before receiving ‘first-line’ therapy to ensure that the most appropriate treatment is selected.

NICE has already recommended these two drugs as first-line treatments in people whose tumors are EGFR-TK mutation-positive. However clinical specialists told the independent advisory committee that, in clinical practice, where this group of patients have received erlotinib and gefitinib as first-line treatment, it is unlikely that they would be re-treated with an EGFR-TK inhibitor as part of second-line treatment because of reduced sensitivity of the tumor to these drugs. Clinical specialists also told the Appraisal Committee that a small group of patients may receive a delayed diagnosis of mutation status. Some of these patients have stable disease and it is possible to wait for two weeks for the diagnostic test result, but patients with aggressive disease need immediate treatment before EGFR-TK mutation status is confirmed.

In the new draft guidance, erlotinib is provisionally recommended as an option for treating disease that has progressed in people who have had non-targeted chemotherapy because of delayed confirmation that their tumor is EGFR-TK mutation-positive. Erlotinib in also recommended as a treatment option for people with tumors of unknown EGFR-TK mutation status under certain conditions.

Sir Andrew Dillon, chief executive of NICE, said: “When we update recommendations, it is because new evidence has emerged that improves our understanding of how well a drug works for patients relative to its cost. This draft guidance proposes recommending erlotinib for patients who have received prior non-targeted chemotherapy because their tumor type hadn’t yet been confirmed as mutation positive. It also recommends erlotinib for patients with EGFR-TK mutation-unknown tumors only in certain circumstances.”

He continued: “The ongoing review of these two treatments incorporates new evidence on the clinical and cost effectiveness of erlotinib and gefitinib – the revised recommendations aim to ensure that patients are offered the most appropriate treatments. The provisional recommendations have been issued for further public consultation and the manufacturers and other stakeholders now have an opportunity to consider and respond to the recommendations made by the independent Appraisal Committee.”