Background
cancers, tumor, toxicity, cancer, cancer disease
CANCERS, TUMOR, CANCER, DISEASE, EMA, ONCOLOGY, MALIGNANT DISEASE
Personalized cancer care is rapidly evolving, as the biological understanding of the individual’s cancer disease increases. A deeper understanding of disease and host at the genomic level, coupled with accessible and affordable multiplex analysis of the transcriptome, proteome, and other aspects of the cancer, is leading the way towards new paradigms in the treatment of cancer, relying not solely on the tissue of origin, but on molecular tumor profiling.Although actionable molecular targets are frequent in cancers, the heterogenous distribution across tumor types makes traditional randomized phase 3 clinical trials in precision medicine rare, especially in less frequently encountered molecular targets. However, evidence is mounting through small clinical trials, case series, and case reports that patient outcomes are improved when a targeted treatment is matched to a tumor harboring the molecular target [Several challenges exist for identifying and providing the relevant treatment to the patients at need. Many oncologists and pathologists have sparse access to comprehensive genomic profiling for screening purposes and experts for interpretation of genomic test reports to guide scientifically informed decisions about the optimal use of targeted agents [List of abbreviationsMatching molecular targets to relevant drugs may improve outcomes in cancer patients although large scale prospective, randomized, controlled trials are yet to be concluded. The randomized phase II trial SHIVA by Tourneau with matched molecular target treatment vs. physicians choice failed to demonstrate any significant different in progression free survival (PFS) between the two arms [The Danish study, CoPPO (Copenhagen Prospective Personalised Oncology) included 500 patients undergoing biopsy followed by whole exome sequencing (WES) and RNA sequencing. One hundred one patients (20%) received matched treatment based on either pathogenic variants or RNA expression levels of targets available in early clinical trials or off-label treatment. Objective response according to RECIST v1.1 was observed in 15 of 101 patients (0% complete response, 15% partial response), with a median PFS of 12 weeks (95% confidence interval, 9.9–14.4) [The growing number of U.S. Food and Drug Administration (FDA) and/or European Medicines Agency (EMA) approved drugs for specific molecular targets in distinct histologies may lead to increased off-label use. Multiple prospective trials have recently been initiated to gather data on safety and outcomes, as well as extensive molecular data. These studies rely on extensive molecular profiling and decision making at molecular tumor boards [The primary aim of this trial is to investigate the anti-tumor activity and toxicity of commercially available, EMA-approved targeted therapies outside the labeled indications in the treatment of advanced malignant diseases harboring specific actionable genomic alterations. This protocol has been prepared according to the Standard Protocol Items: Recommendations for International Trials (SPIRIT) guidelines [