Targeted Treatment of Rare Cancers Based on Genetic Tumor Profiles

A cancer is considered rare if fewer than 6 out of every 100,000 people are diagnosed with it each year. In total, there are about 200 different types of rare cancers. Although each individual type of cancer is rare on its own, these tumors together account for nearly a quarter of all cancer cases in adults. Diagnosing rare cancers poses particular challenges for doctors: These diseases are often poorly understood, there is limited experience with treatment, and there are hardly any standardized treatment guidelines. One reason for this is the lack of inclusion of this patient group in many studies. This is precisely why treatment at specialized centers is particularly important. An earlier study demonstrated that targeted therapy based on comprehensive genetic tumor analysis and the recommendations of a molecular tumor board (MTB) is significantly more effective than standard treatment without an MTB. An MTB is a multidisciplinary case conference that focuses on the analysis of tumors at the molecular level to develop personalized treatment approaches, particularly when standard therapies are not sufficiently effective or are unavailable. It serves to identify targeted therapies based on the tumor’s specific genetic alterations and may also include enrollment in clinical trials or the application for off-label therapies. Off-label therapies involve the use of drugs that have not yet been specifically approved for this type of treatment.

The goal of this study is to determine whether such a molecularly guided therapy, based on the tumor’s genetic characteristics, leads to better outcomes. To this end, the tumor’s entire genome and gene activity are analyzed. The molecular tumor board then evaluates the results and makes treatment recommendations. Previous studies have shown that MTB-based therapies are effective. The RATIONALE study is now investigating when the best time is to initiate an MTB-based therapy—immediately at the start or only after standard therapy has failed. For this purpose, patients are randomly assigned to two groups: either they receive the MTB-based therapy immediately (MPI group) or they first receive standard therapy and switch to the MTB-based treatment if their condition worsens (MPP group). The primary endpoint—that is, the most important measure of whether early therapy is more effective—is assessed using progression-free survival (PFS), which is the length of time during which the disease does not progress and the tumor remains stable. Follow-up as part of the study will continue for approximately 4 years after the study begins.

Eligible participants are patients aged 18 and older with a locally advanced or metastatic rare tumor (epithelial or mesenchymal) for whom curative treatment is no longer an option. In addition, there must be at least one measurable tumor site in the body that is clearly visible on imaging such as a CT or MRI scan. Patients must have already received at least one standard therapy, or there must no longer be an effective standard therapy available according to guidelines. Another requirement is that a fresh tissue sample (biopsy) can be obtained from the tumor, or that a suitable tissue sample containing sufficient tumor tissue has already been frozen within the last 3 months. This sample is necessary for genetic analysis as part of the study.