NEW YORK — More than 40 percent of advanced cancer patients in Norway have responded to targeted treatments after being matched to them through a new diagnostic and clinical trial pipeline.
While that number may change as the program scales — the figure is from the first 40 or so patients from the Improving Public Cancer Care by Implementing Precision Medicine in Norway (IMPRESS-Norway) trial — it illustrates the potential of the approach Norway is taking to bolster precision medicine for advanced cancer patients there.
A review of services in Norway had previously found gaps in the country's ability to implement personalized medicine for cancer patients. "We had very little available in terms of advanced molecular cancer diagnostics," Oslo University Hospital's Kjetil Taskén, who chaired a working group looking into the issue, said. "That was the bottleneck, the ability to do large gene panels or things beyond individual genetic tests."
He and his colleagues from across disciplines and with input from executives and regulators have set up a program through which all patients in the country with advanced cancer are referred for extended molecular profiling for tumor biomarkers and matched, if possible, to targeted treatments being studied as part of the IMPRESS-Norway trial or other clinical trials.
"The classical clinical trial models … are not going to work that well [for precision medicine] because the principle in such trial designs is you set the inclusion and exclusion criteria so that, for the purpose of the trial, all the patients are similar, which is why one can draw randomly into two or more groups and compare two treatments or treatment and placebo," Taskén said. "Whereas here the principle is that all the patients are different and you treat them differently."
The working group Taskén chaired identified three items that needed to be addressed: the ability to conduct testing with larger gene panels, attracting clinical trials, and the need to incorporate personalized medicine into typical clinical cancer care.
Following a series of national meetings, they developed a program with four main parts — the diagnostic infrastructure of InPreD-Norway, the clinical trial IMPRESS-Norway, the associated INSIGHT-INCLUDE research program, and the CONNECT public-private partnership — that span the personalized cancer care pipeline, which they recently described in a letter in Nature Medicine.
Under InPreD-Norway (Infrastructure for Precision Diagnostics for Norway) two of the six university hospitals in the country are to be hubs that perform whole-genome sequencing, while all six university hospitals test with large gene panels. Smaller hospitals, meanwhile, conduct pathological analyses and smaller gene panels.
According to Taskén, this approach is now being scaled up. The hospitals are now offering Illumina's TruSight Oncology 500 panel, which includes more than 500 genes — these tests are further reimbursed through Norway's public healthcare system. "When this is built out and scaled, we will screen more patients compared to the population than in many other countries in Europe," he added.
That, he said, will also add to researchers' and clinicians' knowledge of the population-wide frequency of different mutations in various cancers and long-term outcomes, since patients can be followed over time through the public healthcare system.
At the same time a National Molecular Tumor Board is built into InPreD-Norway. It currently meets twice a week, once with diagnosticians and once with clinicians, to discuss about 10 to 15 cases a week. Taskén estimated that will ramp up to about 50 cases per week as the program grows. As they learn more, some cases will likely be reported without discussion, and as the program scales even further, regional molecular tumor boards may be established.
In its first year, more than 300 patients have gone through the National Tumor Board, Taskén noted and more than 70 patients have been added to the IMPRESS-Norway treatment cohorts. IMPRESS-Norway, which is publicly funded and has been open for a year, is modeled on the Netherlands Drug Rediscovery Protocol (DRUP) trial and is similar to trials being conducted by other Nordic countries.
The study includes different targeted therapies provided by a number of companies. The trial began with eight drugs from Roche, but other pharmaceutical companies — Novartis, Incyte, Eli Lilly, and AstraZeneca — have since joined. Currently, 16 drugs are included in the study, and 23 drugs are expected to be included in the trial by the end of the year. All the drugs included are registered drugs that are being investigated outside their current indications, Taskén noted.
The trial so far has identified a targeted therapy for about a quarter of patients, and early data from the first 40 patients in IMPRESS-Norway at 16 weeks indicates that more than 40 percent have responded to their drug. Taskén cautioned, though, that this is early data.
He further noted that about 15 percent of patients have qualified for other clinical trials, for compassionate-use drug programs, or have had a revised diagnosis pointing them toward a new treatment.
In addition to the other two arms of the program — which focus on investigating other aspects of cancer precision medicine such as how to develop control cohorts and its ethical and legal ramifications as well as a public-private partnership for policy and other discussion — other projects are also being folded into this effort.
For instance, though InPreD-Norway uses Illumina's TruSight Oncology 500 panel, IMPRESS-Norway has an ongoing research collaboration with Roche and Foundation Medicine in which they are running a parallel liquid biopsy pipeline, allowing them to evaluate both liquid and solid biopsies. The program will start a similar project with Illumina to examine circulating tumor DNA-based diagnostics.
In the future, Taskén added that they want to fold in additional up-and-coming diagnostic approaches. "We think drug sensitivity screens, protein biomarkers, and all other things should come in on top of genomics to see: how we can go further beyond what genomics and transcriptomics can give in terms of patient benefit?" he said.