Advice

The technology

The technology

Caris Molecular Intelligence (CMI, Caris Life Sciences) is a solid tumour biomarker analysis service. It is intended as a tool to aid decision-making and help identify the best treatment plan for each patient. CMI was marketed as Target Now until 2013.

CMI uses a number of tumour profiling techniques to analyse protein, RNA and DNA in the tumour:

  • immunohistochemistry, to determine level of protein expression

  • in situ hybridisation, to detect deletions and amplifications in a specific set of genes

  • RNA sequencing, to identify fusions and rearrangements of 53 genes

  • next-generation sequencing to detect DNA mutations in 592 genes, amplifications in 442 genes, total mutational load and microsatellite instability.

The service is updated over time to represent changes in clinical experience and technological feasibility. A full list of the biomarkers analysed by CMI is available on the company's website.

CMI uses a formalin-fixed paraffin embedded (FFPE) biopsy, ideally taken within 6 months of profiling, which is sent (using a Caris specimen shipper kit) to the Caris laboratory in the US for analysis. CMI uses a proprietary algorithm to generate a patient report, which is sent electronically to the clinician within 14 days of receiving the sample and all relevant documents. The patient report comprises:

  • A summary of important findings, including lineage-relevant biomarkers and which chemotherapies, immunotherapies, hormone therapies or targeted therapeutics may be effective against the tumour.

  • Details of supporting evidence for each therapy and biomarker, grouped by those with potential benefit, lack of benefit or uncertain benefit.

  • A list of any ongoing clinical trials that match the patient's biomarker expression profile (using the company's proprietary Clinical Trials Connector service).

  • Appendices with full assay results, value information and technical details for each biomarker and technology.

The report is sent to the clinician with a written consultation from a member of the Caris medical team. Caris also offers a telephone call to the clinician to discuss the individual case in the context of treatment history and available treatment options.

Innovations

CMI is done in a centralised laboratory, covering a wider range of molecular testing techniques than may be available in a local laboratory. The results are analysed and summarised in a single report, so the ordering clinician does not need to collate results from multiple tests. The report includes a list of ongoing clinical trials that match the patient's biomarker expression profile, which means that its usefulness will depend on the number of included trials which are open to NHS patients.

If standard treatments in line with existing guidance have failed but the patient is still fit for further therapy, CMI profiling can identify which of the existing chemotherapies may be of benefit for the patient, based on ongoing research. This information may not currently be available to the oncology treatment team and some of these drugs may not have been considered for use in the specific tumour site before. Treatment decisions based on CMI would represent a shift from therapy based on tumour site to a precision medicine approach based on the unique molecular characteristics of a patient's tumour.

Current NHS pathway

People with locally advanced or metastatic cancer may have 1 or more lines of chemotherapy as standard treatment. For example, the NICE guideline on colorectal cancer includes chemotherapy regimen recommendations for advanced and metastatic disease. Regimens involving oxaliplatin and irinotecan in combination with fluoropyrimidines should be offered as first- and second-line treatments, based on anticipated side effects and patient choice. Other options are raltitrexed for patients who cannot have fluoropyrimidines or folinic acid, and capecitabine and tegafur with uracil.

There is no current guidance or standard NHS pathway for locally advanced or metastatic cancer in people who have exhausted all standard lines of therapy but who remain fit enough for further treatments. Some molecular profiling tests are used currently (for example, FISH or histopathology) for certain cancer types to test whether it is likely that the patient's cancer will respond to a particular chemotherapy drug. In addition, the 100,000 Genomes project (Genomics England) can provide similar sequence data on the tumour and clarify whether certain pathogenic mutations are germline or somatic. However, this information does not include the association between a detected abnormality in the molecular profile and a treatment recommendation.

The NICE cancer service guideline on improving supportive and palliative care for adults with cancer states that the final choice of treatment should be guided by patient preference. NICE also has a series of 'improving outcomes' guidelines for site-specific cancers.

NICE is aware of the following CE‑marked devices that appear to fulfil a similar function to CMI:

  • Foundation One (Foundation Medicine)

  • OncoDEEP (OncoDNA).

Population, setting and intended user

CMI is designed to be used for people with locally advanced or metastatic cancer in secondary or tertiary care settings who have no other standard care options remaining, but who are fit enough to consider further treatment. It is not indicated for use in de novo treatment planning because it uses a non-site-specific approach to treatment based on molecular profile, rather than exploring the use of standard care regimens by tumour site.

The CMI report would be requested by an oncologist, pathologist or histopathologist, through a requisition form sent to Caris. Pathology laboratory staff would prepare the biopsy sample using standard sample fixation techniques.

Costs

Table 1 Cost of CMI

Product/device

Cost (excluding VAT)

Additional information

CMI

£5,800, including the full report, a consultation between a member of the Caris medical team and the ordering oncologist, and all sample shipment costs.

Caris Life Sciences offers a discount of £775 for prepayment.

There are no additional consumables or maintenance needed to use the product. The only training that would be needed is on preparation of the shipping kit to be sent.

Biopsy (only for patients who have not had a biopsy sample taken within 6 months of CMI being done)

The cost of biopsy varies by cancer type. The weighted cost of all biopsy procedures for cancer patients (excluding biopsy for diagnostic purpose) is calculated as £251 (NHS reference costs 2015/16). This includes direct cost, indirect cost and overhead costs.

Costs of standard care

Standard care in this indication is determined during multidisciplinary team meetings and based on clinician and patient choice. The weighted cost of a multidisciplinary team meeting for cancer patients is £111 (NHS reference costs 2015/16).

Resource consequences

No published evidence on the resource consequences of adopting CMI was found.

Two specialist commentators estimated that it currently takes 1 to 8 weeks to test for molecular-targeted therapies, depending on the test requested.

Caris returns the CMI report within 14 days of receiving the sample, and it takes 2 to 3 days for a shipment sent from England to arrive at Caris. A specialist commentator estimated that preparing a sample for shipping using an existing FFPE biopsy would take around 30 minutes, but that retrieving a stored biopsy from the local pathology service may take 7 to 10 days. Preparing a newly taken FFPE biopsy for shipping would take 3 to 4 days.

The time taken to prepare the sample, send it and receive the report all need to be taken into account when planning treatment. If the timings are not properly managed, some patients could start treatment while waiting for the CMI report, which could lead to their treatment needing to change.

A specialist commentator estimated that the total additional time needed for sample preparation and analysis of a CMI report would be around 1 hour per patient.

No additional facilities or technologies would be needed to adopt CMI.

CMI is currently available privately to people who choose to pay or for people enrolled in a CMI clinical trial. It is also currently used for research purposes in approximately 30 NHS hospitals. Some private health insurance companies cover CMI on a case-by-case basis.