National Harbor, Md.—While immunotherapy has been extremely successful for some patients, it’s still early with regard to understanding cancer immunology and predicting which patients will benefit and what time course of treatment is best, according to a panel of experts at the 2016 annual meeting of the Society for Immunotherapy of Cancer.
When Genentech was conducting clinical trials of atezolizumab (Tecentriq) that provided treatment for a year, the investigators found interesting results, said Daniel S. Chen, MD, PhD, the vice president and cancer immunotherapy franchise head in product development for the company. Some patients appeared to have deep, durable responses that continued after therapy ended; some patients who responded to therapy progressed after stopping therapy but could be successfully re-treated; and other patients who progressed after stopping therapy could not be successfully re-treated. “When we looked at the data set, there was no particular clinical feature or biomarker that could help us define which patient would fall into which group,” he said. For that reason, he said, the company left the duration of therapy up to physicians and their patients.
A critical issue with the variety of agents is how to identify patients who will do well with immunotherapy, added Jon M. Wigginton, MD, the chief medical officer for MacroGenics, Inc., in Rockville, Md. “That said, there are not magic, clear answers regarding I-O [immuno-oncology] biomarkers that can be used consistently across multiple agents right now. It will take time to define these.”
Oncologists struggle to understand the ideal duration of immunotherapy, noted Roy S. Herbst, MD, PhD, a professor of medicine, the chief of medical oncology and associate director of translational research at Yale Cancer Center, in New Haven, Conn. Some patients can be on therapy for only a few months and do well while others do not; their physicians have to decide whether or not to put them back on therapy. “It would be nice if we had the parameters to know if it would benefit or not,” he said. The National Cancer Institute of Canada is sponsoring a trial to examine continuous versus noncontinuous checkpoint inhibition, according to Dr. Wigginton.
Whether stopping or initiating therapy, “moving too quickly to a one-size-fits-all approach in an area as new and variable in terms of the patient response is going to limit results and access to therapy,” cautioned Kirsten Axelsen, the vice president for global policy at Pfizer.
Intensive efforts are underway to develop additional biomarkers to help predict response to therapy, Dr. Chen said. The work is much more difficult than identifying typical markers of cancer such as EGFR mutations, he said. “If you think of the biology and complexity of the immune response, the ability to really generate an immune response in any patient with cancer … is actually remarkable.”
“I would agree,” Dr. Herbst said. “As good as this is, in lung cancer it’s still the first or second inning in an over nine-inning game.” He said 45% of patients expressing PD-L1 respond to therapy, but what about the other 55%, or patients who do not express PD-L1 but still benefit from immunotherapy? “It’s not the whole story but the logistics are so tough, and they’re expensive.” Biomarkers that predict success with combination immunotherapies also are needed, the panelists noted. Patterns of response to ipilimumab plus nivolumab are variable and could serve as a “rich source of insights into how a highly active functional T-cell compartment can induce tumor regression,” Dr. Wigginton said. High-throughput platforms will be needed to search for multiple biomarkers in small bits of biopsied tissue, Dr. Chen added.
Investigators should stay open-minded about understanding the human immune response to cancer, Dr. Chen said. “There’s enormous biology to be understood out there, and having diversity of thought now will probably help us get to the right end point in the future.”
By Karen Blum