Predictive Biomarkers for Nivolumab Treatment in Metastatic Renal Cell Carcinoma
Abstract
On November 23, 2015, the US Food and Drug Administration (FDA) approved nivolumab to treat advanced kidney cancer. The approval came following the results of a trial, called CheckMate 025, that compared the survival of patients who received nivolumab to those who received everolimus, which was a standard of care treatment modality. The study was done among individuals who were diagnosed with advanced kidney cancer, and who had previously been treated with one or more drugs. In that study, the investigators found that the survival of patients treated with nivolumab was better than those treated with everolimus. Despite these benefits, only a subset of patients responded to the nivolumab treatment in that trial. Within the study, that proportion was determined to be around 25%. In an attempt to get more individuals to respond to immunotherapy, investigators tested the combination of ipilimumab (another type of immunotherapy) and nivolumab vs. sunitinib in patients with advanced kidney cancer. As hoped, the combination therapy resulted in more patients responding to the combination, but not without the occurrence of significant serious side effects. Consequently, clinicians are hoping to find ways to be able to identify patients (before therapy) that are more likely to respond to just nivolumab, and thereby sparing patients who are unlikely to respond to go through the unnecessary treatment and potential toxic side effects of the combination of nivolumab+ipilimumab. The advances of biomarker technologies have made cancer treatment evolve from the classic "one-drug-fits-all" to a more personalized strategy where treatment regimen is driven by individual biomarker expression profiles. Right now, there is no biomarker used in routine clinical practice for selecting patients who are likely to benefit from nivolumab for advanced kidney cancer. Working towards this goal, our team previously identified several biomarkers found in the blood and in the tumor tissues. However, these studies were performed in smaller clinical datasets with a limited number of patients. Moreover, biomarker status was not always available in the control population (i.e., patients not treated with the experiment of interest), which is an important detail in determining the real clinical utility of these biomarkers. Hence, the goal of the current proposal is to validate our initial findings by using samples obtained from the CheckMate 025 trial, a randomized phase 3 trial that contains a control arm (i.e., those treated with everolimus). We will test the relationship between the biomarkers we studied before with the time to progression of disease and time to death. Moreover, we will be measuring how each patient responds to the drug through a set of established rules that define when cancer patients respond, stay stable, or worsen during treatment. From a worldwide perspective, both the European Medicines Agency (EMA) and the FDA are encouraging the development of biomarkers as companion diagnostics in general practice. From the economical burden and cost-effectiveness point of view, there is a clear compelling argument to develop and test biomarkers that can be accurately and safely used in clinical practice to identify the responsive subpopulation. While a handful of biomarkers have reached clinical practice in other cancers, there is currently no predictive biomarker during patient counselling and treatment management decision in kidney cancer. In other cancers, the identification, development/identification, and validation/reconfirmation of biomarkers based on rigorous scientific studies and tested in focused, well-designed clinical trials allowed more efficient clinical development, as well as an associated reduced failure rate of drug development. For the kidney cancer patient, the benefits of completing this proposal will be enormous, reflecting the concept of the "right drug for the right patient."
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Oct 29, 2018
- Source ID
- W81XWH1810480
Entities
People
- Toni K Choueiri
Organizations
- Dana–Farber Cancer Institute
- United States Army