Immuno-oncology is a unique approach to cancer treatment that leverages the body’s immune system to help fight cancer. Immuno-modulating agents such as interleukin-2 (IL-2) and interferon (IFN) have been used in the treatment of some solid malignancies for years, but their use has generally been limited to cancers that are immunogenic, such as melanoma and kidney cancer. More recently, immune checkpoint inhibitors have changed the landscape of immunotherapy, and emerging therapies such as chimeric antigen receptor T-cells (CAR-T), dendritic cell vaccines, and bi-specific T-cell engager (BiTE) antibodies are pushing the envelope even further.
In 2016, the cancer immunotherapy market was estimated to be $41 billion, and it is expected to grow to nearly $119 billion by 2025. Small and midsized biopharmaceutical companies will play a critical role in this growth, but will need to overcome critical hurdles that are inherent in developing immunotherapeutic agents. Because immunotherapy innovations work differently than chemotherapy, they require different standards for evaluating their safety and effectiveness. Understanding these standards—and the other major challenges of immuno-oncology studies—is critical to clinical trial success.
Evaluating response to cancer immunotherapies
When evaluating oncology drugs, four distinct response patterns are generally associated with favorable overall survival:
- Response in baseline lesions
- Stable disease with slow decline in tumor volume
- Response following an initial increase in tumor volume
- Response following the appearance of new lesions
Traditionally, response and efficacy with oncology agents has been measured by a set of published rules known as Response Evaluation Criteria in Solid Tumors (RECIST). However, these criteria do not easily apply to immuno-oncology agents because of the kinetics of the anti-tumor response associated them. Unlike conventional cytotoxic therapies that may trigger rapid tumor shrinkage due to direct killing of cancer cells, immuno-oncology drugs stimulate immune cell responses that may take several months to occur. As a result, patients may exhibit an initial increase in tumor burden followed by tumor shrinkage, a phenomenon called the flare effect.