2 Clinical need and practice
2.1 Approximately 32,000 people are diagnosed with lung cancer in England each year. Around 72% of lung cancers are non‑small‑cell lung cancers, which can be further classified into 3 histological subtypes: large‑cell undifferentiated carcinoma, squamous cell carcinoma and adenocarcinoma. Most lung cancers are diagnosed in the later stages, with 21% of people presenting with locally and regionally advanced disease (stage IIIB) and 48% presenting with advanced disease (stage IV) in which the cancer has spread to other parts of the body. The 5‑year survival rates for people presenting with stage IIIB or stage IV non‑small‑cell lung cancer are around 7–9% and 2–13% respectively.
2.2 Non‑small‑cell lung cancer can test either positive or negative for an epidermal growth factor receptor tyrosine kinase (EGFR‑TK) mutation. EGFR‑TK is a selective target for inhibiting cancer: in normal cells, EGFR‑TK is controlled, but the overexpression of EGFR‑TK caused by the mutation is considered a critical factor in the development and malignancy of non‑small‑cell lung cancer tumours. Overexpression of EGFR‑TK has been detected in 10–15% of non‑small‑cell lung cancers.
2.3 For most people with non‑small‑cell lung cancer, the aims of therapy are to prolong survival and improve quality of life. For people with locally advanced or metastatic non‑small‑cell lung cancer that has progressed after chemotherapy, NICE's lung cancer guideline recommends that docetaxel monotherapy should be considered if second‑line therapy is appropriate. NICE technology appraisal guidance on erlotinib for the treatment of non-small-cell lung cancer recommends erlotinib with a patient access scheme as a second-line treatment option for non‑small‑cell lung cancer as an alternative to docetaxel. It does not recommend erlotinib for the second-line treatment of locally advanced or metastatic non‑small‑cell lung cancer in patients for whom docetaxel is unsuitable (that is, if there is intolerance of or contraindications to docetaxel) or for third‑line treatment after docetaxel therapy. In the terminated NICE technology appraisal on gefitinib for the second-line treatment of locally advanced or metastatic non-small-cell lung cancer, NICE was unable to make a recommendation for gefitinib as a second‑line treatment option for people with non‑small‑cell lung cancer because the company did not provide an evidence submission.
2.4 Clinical practice has changed since the publication of NICE technology appraisal guidance on erlotinib for the treatment of non-small-cell lung cancer because the identification of a tumour's EGFR‑TK mutation status has become an important prognostic factor. In the NHS, most people with non‑small‑cell lung cancer obtain a histological diagnosis for their tumour before first‑line therapy to ensure that the most appropriate treatment regimen is considered. People with non‑small‑cell lung cancer are also tested for EGFR‑TK mutation status at diagnosis. NICE recommends first‑line treatment with an EGFR‑TK inhibitor in people with non‑small‑cell lung cancer whose tumour tests positive for EGFR‑TK mutations (see NICE technology appraisal guidance on gefitinib for the first-line treatment of locally advanced or metastatic non-small-cell lung cancer, erlotinib for the first-line treatment of locally advanced or metastatic EGFR-TK mutation-positive non-small-cell lung cancer and afatinib for treating epidermal growth factor receptor mutation-positive locally advanced or metastatic non-small-cell lung cancer). In clinical practice, re‑treatment with an EGFR‑TK inhibitor is unlikely to be considered for patients whose tumour tests positive for EGFR‑TK mutations and has progressed after first-line treatment. Consequently, EGFR‑TK mutation status is increasingly being considered in the design of lung cancer clinical trials (for example, prospective recruitment of EGFR‑TK mutation‑positive or EGFR‑TK mutation-negative populations, or using EGFR‑TK mutation status as a stratification factor).