Even though we have made great strides in the fight against cancer, improved survival remains a challenge for some advanced malignancies. The five year survival remains poor for many patients with metastatic solid tumors. Surveillance, Epidemiology, and End Results (SEER) program data from 2014 show the five year survival for lung, colorectal, kidney and renal pelvis, and melanoma to be 3.9, 12.5, 12.3 and 16 percent respectively. Immuno-Oncology therapies are being investigated to utilize the body’s own immune system to fight diseases. Currently, there are over 900 oncology clinical trials of immunotherapy in various phases of development. Malignant melanoma, renal cancer, and prostate cancer are potentially immunogenic, which makes them good candidates for immunotherapeutic approaches as well as many other disease states under investigation.
The history of immunotherapy dates back to 1796 when Edward Jenner used cowpox to induce immunity to smallpox. In 1890, Coley demonstrated that bacterial products (Coley toxins) had benefits for inoperable cancers which led to the application of Bacillus Calmette-Guerin (BCG) in the 1960’s. In 1986, Interferon Alpha was approved as Hairy cell leukemia cancer immunotherapy. Interleukin-2 was approved in 1998 for the treatment of renal cell carcinoma and melanoma. Then we had the birth of the monoclonal antibodies bevacizumab and cetuximab in 2004, followed by panitumumab in 2006. The first cellular immunotherapy was approved for prostate cancer (Sipuleucel-T) in 2010. Ipilimumab/Anti CTLA-4 was approved for advanced melanoma in 2011. Now we have the first programmed cell death protein 1 (PD-1) monoclonal antibody inhibitors approved in 2015, nivolumab (Opdivo) and pembrolizumab (Keytruda).
These two new PD-1 inhibitors are currently indicated for the treatment of advanced melanoma and non small cell lung cancer. These agents also have activity in a variety of other disease states and are currently being evaluated in numerous clinical trials. In addition to the development of anti-PD-1 agents, there are agents being developed that target the PD-1 receptor and its ligands (PD-L1/2). Immuno-Oncology therapies have the potential to be used as monotherapy or part of combination regimens. Immuno-Oncology therapies are designed for various specific targets in the antitumor immune response. Combinations of complimentary I-O therapies with chemotherapy, radiotherapy, and targeted therapy have the potential to enhance antitumor effects. One can imagine the complexities of incorporating these new agents into the treatment of various diseases as more agents are developed and incorporated with the traditional pillars of cancer treatment.
This new frontier of medicine will require specialized education so that we can understand the immune system, its relationship to different tumor types, how these new agents interact with the immune system, how to identify and manage immune related events, and to develop and provide the necessary tools for our clinicians and patients. New England Cancer Specialists (NECS) has expertise with these new agents and clinical trials exploring the use of these agents in other disease states. Patients will benefit from the latest advances in cancer care at NECS where our goal is your best outcome.