Optimal Treatment by Invoking Biologic Clusters in Renal Cell Carcinoma (OPTIC RCC)
Abstract
Background and Rationale: Patients with kidney cancer that cannot be surgically removed and/or that has spread to organs beyond the kidney have a high risk of dying from their cancer. Such patients are typically offered medicine to shrink their tumors, relieve cancer-related symptoms, and improve survival. Most patients receive an intravenous immunotherapy drug (an anti-PD-1 antibody), designed to release the brakes on the immune system and thus promote their immune system to attack their cancer, plus a second drug. The second drug is either (1) a second intravenous immunotherapy drug designed to further stimulate the immune system (an anti-CTLA-4 antibody called ipilimumab) or (2) an oral medication that poisons blood vessels that feed the tumors. Some patients have marked shrinkage of their tumors that is long-lasting when treated with a pure immunotherapy strategy. However, other patients do not respond to the pure immunotherapy strategy but may have tumor shrinkage when their regimen includes a tumor blood vessel poison. There are few tools available to physicians and patients to help guide this decision. Factors that currently may drive this decision include physician familiarity with a particular regimen, physician s interpretation of the existing data, patient s medical history and other medical problems, and clinical factors. However, there are no head-to-head comparisons of these two treatment strategies and no tools that can match the biology of an individual patient s tumor to one of these two strategies. The inability of physicians and patients to make an informed decision regarding which strategy is most likely to benefit an individual patient represents an important clinical problem. The kidney cancer community needs new tools to aid physicians and patients in making this critical decision. Relative to healthy cells, cancer cells have a unique genetic signature. Our group has extensive use in measuring the genetic signature of kidney cancer. Recently, we analyzed the genetic signatures of tumors from a large clinical trial and observed that a certain genetic signature correlated with improved response to immunotherapy. Other genetic signatures include high expression of tumor blood vessels, suggesting these tumors require a tumor blood vessel poison in their treatment strategy. In the current protocol, we seek to evaluate whether these genetic signatures can be used as a precision tool to match individual tumors to either a pure immunotherapy treatment regimen or an immunotherapy/tumor blood vessel poison. Objectives: The purpose of this study is to test our hypothesis that a new tool that measures the genetic signature of kidney cancer tumors can precisely match a patient to a pure immunotherapy regimen or an immunotherapy/tumor blood vessel poison combination. Relative to previous studies that gave either the pure immunotherapy regimen or the immunotherapy/tumor blood vessel poison combination to all patients, we predict that using gene expression signatures to match tumor with treatment will lead to improved patient outcomes. KCRP Focus Areas: The current proposal aligns well with the FY21 KCRP Focus Areas: Identify and develop new strategies for screening, early-stage detection, accurate diagnosis and prognosis prediction of kidney cancers, with examples including biomarkers and imaging. The use of the genetic signature of tumors to match patients with treatments is a prime example of novel biomarker development. Develop novel therapeutic strategies for the treatment of kidney cancer, such as novel drug targets, therapeutic modalities and agents, treatment combinations and drug delivery systems. There are currently no molecular biomarkers approved for clinical use in kidney cancer. The use of our proposed genetic signature tool to match patients with the best therapy clearly represents a novel therapeutic strategy in kidney cancer. Clinical Applications, Benefits, and Risk
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 28, 2022
- Source ID
- W81XWH2211033
Entities
People
- Brian I. Rini
Organizations
- United States Army
- Vanderbilt University