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

Level of innovation

Two specialists thought that plasma epidermal growth factor receptor (EGFR) technology was innovative and represented a paradigm shift in managing lung cancer. One stated that implementing plasma EGFR testing would lead to changes in testing for other cancers. Two specialists believed only digital polymerase chain reaction (dPCR) plasma testing would be a major variation.

Two experts suggested next-generation sequencing (NGS) could supersede this technology in the future and mentioned several tests as current or future competing technologies. One specialist said that they believe mutation testing on 1 gene locus was outdated and NGS on plasma samples would allow for decision-making based on a more appropriate range of somatic variations. However, 1 specialist mentioned that NGS takes significantly longer than plasma EGFR mutation testing and this could have a detrimental effect on patient health. Finally, another specialist described from their experiences of using NGS and dPCR that the more sensitive methods detect mutations which may not drive tumour progression and therefore, are not clinically relevant.

Potential patient impact

Three specialists noted that avoiding rebiopsy was a significant benefit to patients, with 1 specialist adding that biopsies in people with advanced or metastatic non-small-cell lung cancer (NSCLC) have an increased risk of complications such as pneumothorax. Reducing rebiopsy rates would mitigate some of these complications. Two specialists commented that plasma testing does not allow for ALK and PDL1 mutation status to be assessed. Knowing the status is necessary for NSCLC treatment management and therefore, plasma testing cannot negate the need for an initial tissue biopsy. Two stated the potential for longitudinal disease monitoring and patients having diagnoses faster as potential benefits; 1 believed plasma EGFR testing could replace CT imaging for monitoring, whereas another mentioned that it is more convenient, less invasive and safer for the patient than tissue EGFR testing.

Three specialists noted that plasma EGFR testing would be particularly beneficial for people with disease progression or people whose disease has developed a resistance to their current tyrosine kinase inhibitor (TKI) therapy. Three specialists commented that it could offer more appropriate, personalised treatment options for people unable to have a tissue EGFR test, such as older people or people with poor health.

Potential system impact

Potential system impacts cited by the specialists were reduced need for rebiopsy, fewer hospital visits, more people having the most appropriate treatment and earlier diagnoses. Two specialists thought the reduction in biopsies could result in cost savings and a reduction in biopsy waiting times. Three specialists, however, believed there would be no overall difference in costs compared with the current standard of care. One cited that the decreased diagnostic costs may be offset by increased drug costs from more people being prescribed TKIs.

One specialist explained that as the technology to do these tests is already available in most hospital laboratories, the capital costs would be minimal and they could be used on other cancers. Two specialists commented that implementation of this technology would need more staff in genotyping laboratories, 1 of whom concluded that the costs associated would be minimal, whereas the other stated that staffing costs and implementing a shipping pathway would be balanced by major cost savings from reduced rebiopsy rates. However, another specialist felt this technology would not lead to a cost saving because testing would have to be repeated because of the high rate of false negatives.

Three experts thought no changes to facilities, infrastructure or training would be needed to implement this technology, 2 cited training would be needed and 1 mentioned validation; however, they believe it would lead to minimal extra workload. One specialist commented that plasma EGFR testing could be done in an outpatient setting allowing for convenient monitoring.

General comments

Two specialists believe this technology could replace the current standard of care, 1 believed it could replace the need for repeat biopsy and another 2 thought it would be implemented as an addition to tissue testing, particularly at diagnosis.

One specialist commented that implementing plasma testing for EGFR testing in their laboratory using Roche Cobas had been smooth and relatively easy. They noted that an important practical consideration is preservation of blood samples in blood tubes that prevent cell lysis, which are needed for all plasma EGFR tests. These are more expensive than regular blood collection tubes and not widely used in NHS hospitals. A further 2 specialists cited high costs and reimbursement as issues affecting adoption of this technology across the NHS.

Another specialist noted a major drawback with plasma EGFR testing is the high rate of false negatives for both EGFR‑sensitising and acquired resistance mutations.

Two specialists agreed that plasma EGFR mutation testing could not replace a tissue diagnosis of NSCLC. However, they both stated that in late-stage NSCLC when there are no currently available therapies, plasma EGFR testing could prevent rebiopsy, in particular in people with T790M mutations. One noted that this affects a very small number of patients, although 2 experts suggested that plasma testing may be suited for use in people with late-stage disease as sensitivity increases with tumour burden.

One specialist noted that current plasma EGFR mutation tests do not identify C797X mutations, which are likely to be clinically important as mutation-specific drugs are developed.

Specialist commentators suggested further research is needed into: