Improving public cancer care by implementing precision medicine in Norway: IMPRESS-Norway

Abstract

Background Matching treatment based on tumour molecular characteristics has revolutionized the treatment of some cancers and has given hope to many patients. Although personalized cancer care is an old concept, renewed attention has arisen due to recent advancements in cancer diagnostics including access to high-throughput sequencing of tumour tissue. Targeted therapies interfering with cancer specific pathways have been developed and approved for subgroups of patients. These drugs might just as well be efficient in other diagnostic subgroups, not investigated in pharma-led clinical studies, but their potential use on new indications is never explored due to limited number of patients. Methods In this national, investigator-initiated, prospective, open-label, non-randomized combined basket- and umbrella-trial, patients are enrolled in multiple parallel cohorts. Each cohort is defined by the patient’s tumour type, molecular profile of the tumour, and study drug. Treatment outcome in each cohort is monitored by using a Simon two-stage-like ‘admissible’ monitoring plan to identify evidence of clinical activity. All drugs available in IMPRESS-Norway have regulatory approval and are funded by pharmaceutical companies. Molecular diagnostics are funded by the public health care system. Discussion Precision oncology means to stratify treatment based on specific patient characteristics and the molecular profile of the tumor. Use of targeted drugs is currently restricted to specific biomarker-defined subgroups of patients according to their market authorization. However, other cancer patients might also benefit of treatment with these drugs if the same biomarker is present. The emerging technologies in molecular diagnostics are now being implemented in Norway and it is publicly reimbursed, thus more cancer patients will have a more comprehensive genomic profiling of their tumour. Patients with actionable genomic alterations in their tumour may have the possibility to try precision cancer drugs through IMPRESS-Norway, if standard treatment is no longer an option, and the drugs are available in the study. This might benefit some patients. In addition, it is a good example of a public–private collaboration to establish a national infrastructure for precision oncology. Trial registrations EudraCT: 2020-004414-35, registered 02/19/2021; ClinicalTrial.gov: NCT04817956, registered 03/26/2021.

Astrocytoma (CNS WHO grade 4), IDH‐mutant with co‐occurrence of BRAF p.V600E mutation, and homozygous loss of CDKN2A

“…This is, even for CNS WHO grade 4 IDH ‐mutant astrocytomas, a rather aggressive clinical course with only half of the median survival time of IDH ‐mutant astrocytomas CNS WHO grade 4 and with tumor spread along the entire length of the spinal cord. Given the growing number of combined basket and umbrella studies, such as IMPRESS Norway, 13 in which patients are treated based on a molecular biological rationale, it appears reasonable to suggest that BRAF p.V600E‐targeted therapy is an attractive option for patients with gliomas bearing such a molecular alteration. In support of this view, drugs that specifically target cells expressing the BRAF p.V600E‐mutant protein, such as vemurafenib, have been documented to demonstrate a therapeutic effect in these gliomas.…”

Assessment of Two Commercial Comprehensive Gene Panels for Personalized Cancer Treatment

“…TMB for OCAP was evaluated by Ion Reporter and TMB for TSO500 was evaluated by CLC Genomic Workbench and Illumina Local App using the default settings. The cut-offs for high TMB (>20 mut/Mb), intermediate (5–20 mut/Mb) and low TMB (<5 mut/Mb) were applied according to the protocol for IMPRESS-Norway [ 8 ].…”

“…Clinical trials of new targeted drugs are commonly designed as basket or umbrella trials where patients are enrolled based on a wide selection of mutations [ 5 , 6 , 7 ]. For example, an ongoing nation-wide Norwegian basket trial on precision medicine enrolls previously treated advanced cancer patients based on detection of a tumor mutation that can be targeted by the drugs available through the trial (currently 13 drugs, IMPRESS-Norway [ 8 ]). Additionally, patients with high TMB may receive immunotherapy through this study.…”

Strategies to decrease inequalities in cancer therapeutics, care and prevention

“…Processes were initiated, both bottom‐up and top‐down, to implement precision cancer medicine. In addition, connections were made with similar efforts in the Nordic countries and in the Netherlands, and a public‐private partnership was established [33,34].…”