This article has been updated with the number of patients involved in the study and timeline details.
NEW YORK – A group of researchers in Switzerland has set out to show the feasibility of incorporating a comprehensive suite of tumor profiling technologies into the treatment decision-making process for cancer patients and prove that such a multi-omics approach will add value over standard approaches and improve precision therapy decisions.
The researchers outlined the design and aims of the Tumor Profiler study, dubbed TuPro, in Cancer Cell on Thursday.
The TuPro study is rooted in the researchers' notion that oncologists are not making the best personalized treatment decisions for patients by relying just on targeted DNA profiling using next-generation sequencing and digital pathology-based tests. The researchers within the TuPro consortium hypothesized that integrating a more comprehensive suite of omics tests could lead to a more complete understanding of patients' tumors, including providing insights into the tumor microenvironment, heterogeneity, and ex vivo responses to certain drugs. This, in turn, could help inform the best course of treatment.
To determine the feasibility of integrating these newer, non-standard technologies into routine diagnostics and precision oncology treatment decision-making, the TuPro researchers designed a prospective, observational study funded and conducted by the TuPro consortium, which includes Roche, ETH Zurich, University of Zurich, University Hospital Zurich, and University Hospital Basel.
Over the course of three years, a suite of tests will be applied to tumor samples collected from 240 patients total, including roughly 120 patients with metastatic melanoma, 80 with metastatic epithelial ovarian cancer, and 40 with acute myeloid leukemia. Recruitment for the study began in 2018, and as of today, the melanoma cohort has been fully enrolled and the ovarian cancer and AML cohorts are expected to complete enrollment within the next few months. Results from the melanoma cohort are expected to be published during the second half of 2021. According to Anja Irmisch of the University Hospital Zurich and other authors of the Cancer Cell commentary, these three cancer types were selected for the study "based on the potential clinical benefit and availability of sufficient tumor material for simultaneous analysis across all technologies."
The suite of technologies in the TuPro study feature single-cell RNA and DNA sequencing; bulk proteotyping; single-cell CyTOF protein-based analyses; digital pathology; imaging mass cytometry; two ex vivo, single-cell resolution drug response profiling technologies, including pharmacoscopy and 4i (iterative indirect immunofluorescence imaging); bulk RNA sequencing; and targeted DNA sequencing of both the tumor and blood-derived cell-free DNA.
The test results will be analyzed in what the researchers are calling a "fast diagnostic loop," during which the data are compiled into a molecular research report for each patient and presented to a multidisciplinary pre-tumor board for treatment decision-making. The pre-tumor board considers three different levels of evidence and makes treatment recommendations for each.
Treatment recommendations in the first level will have to meet standard clinical guidelines or fall within what is already recommended by the European Society for Medical Oncology. Therapies in the second level will comprise standard approaches plus emerging clinical approaches, and the third level will include approaches that meet the second level of evidence and are further supported with the data gleaned from the suite of TuPro technologies. All of these recommendations plus a summary of the pre-tumor board discussion will then be presented to an official tumor board to make the final treatment recommendation for the patient.
Differences in treatment recommendations between evidence tiers will help the researchers assess the clinical utility of their technologies, while the long-term follow-up patient data will allow them to assess how the diagnostic approach affects patients' outcomes. Over the course of six months, the researchers will collect outcomes data, as well as molecular data, ideally discovering novel biomarkers for treatment response in the process.
In terms of drug response profiling, patients' samples will be screened for responses to a "cancer-type-specific set of approved or promising off-label cancer drugs, alone or in combination." According to the authors, the inclusion of the already well-established approaches, including targeted DNA sequencing, will allow for a comparison of TuPro findings and results from past large-scale cohort studies, ultimately shedding light on the added value of the TuPro tests.
Notably, the researchers will aim to complete all TuPro tests within a clinically relevant turnaround time, which they define as within four weeks between a patient's surgery and the tumor board recommendation. They further claim that their comprehensive diagnostics infrastructure "has the potential to become routine in a few years, the same way genome and exome sequencing are now routine tests." This study, while interrogating the value of the multi-omics approach, will also allow for an assessment as to whether this timing and routine integration are indeed feasible.