A further set of updated draft guidance has been published (Thursday 7 August), following a previous consultation. The new draft guidance provisionally recommends erlotinib as a treatment option for people with non-small-cell lung cancer that has progressed after prior chemotherapy in specific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 tumours.

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).

Clinical practice has changed since the original guidance on erlotinib and gefitinib was published; people with non-small-cell lung cancer have their tumour 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 tumours 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 tumour to these drugs. Clinical specialists also told the 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 2 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In the new draft guidance, erlotinib is provisionally recommended as an option for treating disease that has progressed in people who have had non-targeted chemotherapy because of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 tumour is EGFR-TK mutation-positive. Erlotinib in also recommended as a treatment option for people with tumours of unknown EGFR-TK mutation status under certain conditions (1).

Commenting on the second draft guidance, Sir Andrew Dillon, Chief Executive at 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 tumour type hadn’t yet been confirmed as mutation positive. It also recommends erlotinib for patients with EGFR-TK mutation-unknown tumours only in certain circumstances.

“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.”

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Notes to Editors

1.    Appraisal Committee’s preliminary recommendations: Erlotinib is recommended as an option for treating locally advanced or metastatic non-small-cell lung cancer that has progressed in people who have had non-targeted chemotherapy because of delayed confirmation that their tumour is epidermal growth factor receptor tyrosine kinase (EGFR-TK) mutation-positive, only if the manufacturer provides erlotinib with the discount agreed in the patient access scheme.

Erlotinib is recommended as an option for treating locally advanced or metastatic non-small-cell lung cancer that has progressed after chemotherapy in people with tumours of unknown epidermal growth factor receptor tyrosine kinase (EGFR-TK) mutation status, only if:

• the result of an EGFR-TK mutation diagnostic test is unobtainable because of an inadequate tissue sample or poor quality DNA and
• the treating clinician considers that the tumour is very likely to be EGFR-TK mutation-positive and
• the person’s disease responds to the first 2 cycles of treatment with erlotinib and
• the manufacturer provides erlotinib with the discount agreed in the patient access scheme.

Erlotinib is not recommended for treating locally advanced or metastatic non-small-cell lung cancer that has progressed after non-targeted chemotherapy in people with tumours that are epidermal growth factor receptor tyrosine kinase (EGFR-TK) mutation-negative.

Gefitinib is not recommended for treating locally advanced or metastatic non-small-cell lung cancer that has progressed after non-targeted chemotherapy in people with tumours that are epidermal growth factor receptor tyrosine kinase (EGFR-TK) mutation-positive.

People currently receiving treatment initiated within the NHS with erlotinib or gefitinib that is not recommended for them by NICE in this guidance should be able to continue treatment until they and their NHS clinician consider it appropriate to stop.

About the guidance

1. During consultation on the second Appraisal Consultation Document (ACD), an error was identified in the economic model used to inform the Appraisal Committee’s decision making. It was thought that this may have had an effect on the Committee’s recommendations detailed in the second ACD. Therefore, NICE decided to stop the consultation. An addendum to the Assessment Report explaining the error and presenting the impact on cost-effectiveness results was prepared and consulted upon before the Committee met again to discuss the appraisal. Further information can be found here.
2. Smoking cigarettes, pipes, or cigars is the most common cause of lung cancer. Other risk factors include:

• Smoking cigarettes in the past.
• Being exposed to second-hand smoke.
• Being treated with radiation therapy to the breast or chest.
• Being exposed to asbestos, radon, chromium, nickel, arsenic, soot, or tar.
• Living where there is air pollution.

When smoking is combined with other risk factors, the risk of developing lung cancer is increased.

1. Gefitinib: The cost for a 30-tablet pack of 250-mg tablets is £2167.71.
2. The Committee noted that in NICE technology appraisal guidance 192 (Gefitinib for the first-line treatment of locally advanced or metastatic non-small-cell-lung cancer) there was both robust evidence and an agreed patient access scheme. It understood from the Department of Health that the fixed-price patient access scheme for gefitinib would not apply to the EGFR-TK mutation-positive population whose disease had progressed after prior chemotherapy. As there was no robust evidence or a patient access scheme for using gefitinib for treating non-small-cell lung cancer that has progressed after prior chemotherapy, the Committee agreed that it could not recommend gefitinib in this population.
3. Erlotinib: The cost for a 30-tablet pack of 150-mg tablets is £1631.53. The manufacturer of erlotinib has agreed a patient access scheme with the Department of Health, with a simple discount applied at the point of purchase or invoice. The level of discount is commercial in confidence.
4. The Committee was aware that a published trial directly comparing erlotinib with docetaxel showed erlotinib to be less clinically effective in patients whose tumours test negative for the EGFR-TK mutation. It was aware that for this population, the Assessment Group’s economic model estimated that erlotinib resulted in higher costs and fewer quality adjusted life years (that is, a health loss) compared with docetaxel. In people for whom docetaxel is unsuitable (for which there was no new clinical evidence), erlotinib did not represent a cost-effective use of NHS resources in people with non-small-cell lung cancer whose tumours test negative for the EGFR-TK mutation with the most plausible ICER likely to be over £50,000 per quality adjusted life year gained compared with best supportive care.
5. Approximately 20,000 people are diagnosed with non-small-cell lung cancer in England each year.
6. NICE has produced a pathway on non-small-cell lung cancer.