Plasma EGFR mutation tests for adults with locally advanced or metastatic non-small-cell lung cancer

Innovations

Plasma EGFR mutation tests do not need a biopsy to be taken and are a less invasive alternative to tissue EGFR mutation tests. They can provide testing in people who are unable to, or do not wish to, have a tissue biopsy and whose disease otherwise would remain untested. People may have a lack of available tumour tissue, low-quality tissue sample or poor health making a tissue biopsy infeasible; about 30% of biopsies are classified as 'failed' (PHG Foundation 2017). More than 25% of people with NSCLC in the UK do not have a pathological confirmation of their diagnosis (National Lung Cancer audit report 2016).

Introducing plasma EGFR mutation testing may lead to quicker test results and treatment changes as it removes the need for a tissue biopsy in certain circumstances.

Plasma EGFR mutation testing also avoids problems with tumour evolution and heterogeneity, when the presence of mutations may be missed in a biopsy of a single metastatic site or from using an existing sample. Plasma testing can be repeated easily, allowing for mutation monitoring in people having EGFR‑TKI therapy. This method can detect resistance mutations – predominantly T790M – which may need different treatment. Quantitative plasma EGFR mutation tests can measure the levels of ctDNA, which may be a good predictor of treatment response. This is still being researched and not in clinical use.

Current NHS pathway or current care pathway

The NICE clinical guideline on diagnosing and treating lung cancer recommends that people with suspected lung cancer should be referred urgently for a chest X‑ray. If the results suggest lung cancer, a contrast-enhanced computed tomography (CT) scan of the chest, upper abdomen and lower neck is done to evaluate the degree of mediastinal and chest wall invasion. Further investigations to confirm a diagnosis and to provide information on the stage of the disease are then done. These investigations generally include a biopsy taken from a central or peripheral lesion for histological confirmation and subtyping, but may also include positron emission tomography/CT (PET/CT), endobronchial ultrasound-guided transbronchial needle aspiration (EBUS‑TBNA), endoscopic ultrasound-guided fine needle aspiration or non-ultrasound-guided transbronchial needle aspiration. The tumour sample is used for EGFR mutation testing.

NICE recommends 5 tests that use samples of tumour tissue for identifying EGFR-TK mutations in adults with previously untreated locally advanced or metastatic non-small-cell lung cancer to identify people whose disease might benefit from treatment with EGFR‑TKIs. The guidance notes that tests and methods are evolving, so new ones are likely to appear in the future.

If an EGFR mutation is confirmed, EGFR‑TKIs recommended in NICE technology appraisal guidance such as afatinib, gefitinib or erlotinib can be offered as an alternative to chemotherapy.

If disease progression is seen after first‑line EGFR‑TKI therapy, a repeat biopsy can be done and tested for EGFR T790M resistance mutation. This can tell whether the tumour has become resistant to the first-line EGFR‑TKI, before considering second-line osimertinib, which is recommended as an option in NICE technology appraisal guidance. Testing for EGFR T790M resistance mutation is not routinely done in the NHS.

People who cannot have, or do not want, a tumour biopsy do not routinely have EGFR testing by other means (such as plasma EGFR testing or next-generation sequencing [NGS]) and usually have first-line chemotherapy with a single third-generation drug (docetaxel, gemcitabine, paclitaxel or vinorelbine) and a platinum drug (carboplatin or cisplatin). People who cannot tolerate a platinum combination may be offered single-agent chemotherapy with a third-generation drug.

Population, setting and intended user

Plasma EGFR testing would be used in adults with locally advanced or metastatic NSCLC in secondary or tertiary care settings. Their disease may either be untreated or relapsing after previous TKI therapy. A blood sample would be taken by a phlebotomist. Sample preparation and test procedures would be completed by pathology laboratory staff. The results are used to aid decision-making by clinicians and the patient.

Costs

Resource consequences

The costs of plasma EGFR mutation tests assessed in this briefing are similar to the costs of tissue EGFR mutation tests. However, tissue EGFR mutation tests are based on samples of tumour tissue gathered during biopsy or resection. If there is no readily available tumour tissue, biopsy will be needed to collect tumour tissue. EGFR mutation tests may be cost effective if they reduce the need for tissue biopsy. There is no published evidence on the resource consequences of adopting plasma EGFR mutation tests for patients with NSCLC.

The resource impact statement for NICE's technology appraisal guidance on osimertinib estimates that about 400 people per year whose cancer has the T790M mutation will see their disease progress after first-line treatment with an EGFR‑TKI. If a person's disease progresses after first-line EGFR‑TKI therapy, a positive SuperARMS EGFR T790M liquid biopsy test would indicate suitability for osimertinib therapy, in line with NICE's technology appraisal guidance on osimertinib. Training is needed in the use of all plasma EGFR mutation tests assessed in this briefing; this is standard for implementing any new test and is included in the purchase price for each test.

At the time of writing, Cobas EGFR mutation test is used by 7 NHS hospitals. QX200 AutoDG Droplet Digital PCR Dx system is used by 2 NHS hospitals, and AmoyDx EGFR29 mutation detection kit is used by 1 NHS hospital. None of the other EGFR tests are used routinely in the UK.