A Study to Examine the Value of Broad Agnostic Next Generation Sequencing (NGS) Panel Testing Versus Reimbursed Organ-directed NGS: a Belgian Precision Study of the BSMO in Collaboration With the Cancer Center

Title of the study A study to examine the value of broad agnostic NGS panel testing versus reimbursed organ-directed NGS: a Belgian Precision study of the BSMO in collaboration with the Cancer Centre Study Number BSMO 2020-1 Study Phase Exploratory Sponsor Belgian Society of medical Oncology (BSMO) Treatment None Background and Rationale Several drugs targeting mutated gene products in cancer cells are available to Belgian patients through reimbursement of the drugs and, soon, by reimbursed organ-specific genomic testing.

This context is unfavorable with regard to the following issues:

1. Many more additional drugs with sound scientific rationale and preclinical evidence are available through clinical trials. The relevant genes are generally not included in the reimbursed NGS and ad hoc identification of such patients is extremely difficult and thus severely hampering the accrual in such trials. This denies patients a potential access to innovative treatments from which they could benefit and hampers progress.
2. The same genes can be mutated in other cancer types, other than the reimbursed context, but are not detected due to the organ-specific approach in reimbursed NGS. Examination of these genes with an agnostic approach would give these other patients potential access to the drugs (via various routes, including clinical trials or medical need or otherwise)
3. The broader panels applied by some Belgian platforms (50-100 genes), sometimes in an agnostic approach, do not cover all potentially actionable genes or not all types of actionable variants in these genes.
4. Rearrangements which are highly actionable are not systematically covered in NGS testing, but rely on immunohistochemistry (if done at all) of fusion panels testing that requires additional funding.
5. The various Belgian NGS labs use accredited but heterogeneous methodology and it has been reported that the detection rate of some mutations varies from one site to another.

Therefore, from a patient and oncologist point of view there are current deficiencies that jeopardize optimal access of patients to current or novel genome-driven therapies. Defective identification of sensitive patients limits the implementation of clinical trials and their accrual rates and therefore the attractiveness of Belgium for such trials.

There are more comprehensive commercial platforms that cover a large set of actionable genes (up to hundreds of genes) and the various types of mutations in these genes: sequence mutations, rearrangements, resulting in fusion genes, and gene amplifications.

These commercial vendors have adequate comprehensive methodology but are too expensive (at their current public pricing) for general application. One of these is the platform of Foundation Medicine that builds on a large experience in variant annotation in the US and includes probably all current actionable targets including gene mutations, fusions, MSI, and TMB, all at once in one result. They also report actionability and established or clinical trial treatment options.

To oncologists this is very attractive compared to the fragmented, sequential and very limited current reimbursed conditions.

The investigators estimate that up to 20% of advanced cancer patients could get access to genotype-based treatment that are not covered by the organ-based reimbursement based access to NGS. This can be in the form of off-label application of reimbursed drugs, pharma-sponsored drug development trials that address a specific genotype or pharma sponsored or academic basket trials. Without broad agnostic testing the identification of eligible patients remains extremely difficult. A recent study [A study of genetic characteristics and suitability for targeted cancer treatment (TARGET)] showed that the rate of detection of actionable mutations increased from 28% with local testing to 66% with Foundation Medicine testing.

Objectives

1. To determine the added value of comprehensive and agnostic NGS versus "real-world" practice ("real-world" practice means local testing, no reimbursement for local testing and/or no accessible metastatic lesion) in providing patients with advanced/metastatic solid tumors access molecular guided therapy and/or immunotherapy based on genomic results.
2. To describe the landscape of genomic alterations detected by reimbursed NGS
3. To describe he landscape of genomic alterations detected by comprehensive panel testing
4. To assess the technical success of comprehensive panel testing
5. To describe the uptake of treatments recommended by the molecular tumor board guided by the genomic testing.