On Day 1 at ASCO16, Julie Brahmer, M.D., and David Spigel, M.D., spoke about how to make sure more cancer patients benefit from immunotherapy, as well as considerations for monitoring patients who are undergoing immunotherapy.
In short, patients should no longer be treated in a one-size-fits-all manner solely according to where their tumors are located. Rather, individual patients and tumors should be treated according to their specifics, and additionally, must be monitored for how they are responding to treatments.
Before we look at how best to do that, let’s address an important question: If every patient, and his or her cancer, is different, wouldn’t that mean that each patient would require a custom treatment? Yes and no.
While the collections of individual “trees” that make up cancer “forests” are undoubtedly unique to each patient, the cancer “forests” that arise in different patients often share traits in common. Specific treatments can target specific pathways, and therefore enable us to treat a wide range of patients by targeting traits that are common between tumors.
However, targeting the forest is only half the solution: to fully confront cancer in all its complexity, we must give the painstaking task of targeting the trees to our immune systems. Fortunately, immunotherapy has proven to be an equalizer against cancer’s complexity.
But how do doctors determine individual cancer’s identity? Simply put, they look at biomarkers. Biomarkers can come in many forms, such as genetic mutations or molecules within or on the surface of cells, and can provide very helpful clues. Ideally, these biomarkers could be analyzed using non-invasive methods, but that is not always possible. Before treatment even begins, doctors can look at a patient’s biomarkers and determine the likely course of the disease and, potentially, the optimal course of treatment.
For example, in colorectal cancer the presence of certain types of immune cells in and around tumors is often associated with improved outcomes for patients. This classification, known as the Immunoscore, was shown to be a better predictor of survival than even the stage at which the tumor was diagnosed or if it had invaded surrounding tissue. The trend even held true for brain metastases, where patients with higher Immunoscores were twice as likely to survive.
Biomarkers can guide doctors’ decision making by revealing which treatments might have the best chance of success against that particular tumor. For instance, patients who show high expression of PD-1 or PD-L1 usually respond better to checkpoint inhibitors that block the activity of the PD-1/PD-L1 pathway, though even patients without pre-treatment PD-1/PD-L1 expression have still been found to benefit from them.
Biomarkers also have another use: they can enable doctors to monitor patients and see how they’re responding to treatments. Currently, radiographic scans are used for this, by looking at the size of a tumor over time. With immunotherapy, however, the complexity of an anti-cancer immune response can sometimes cause a tumor to seem to get bigger before it shrinks. This is called pseudo-progression.
Biomarkers that can capture effective anti-tumor responses have immense value. Recently, another promising biomarker was discovered by CRI-funded scientists. Haidong Dong, M.D., Ph.D., lead author of the study and a current CRI grantee, and Svetomir Markovic, M.D., Ph.D., a former CRI grantee, showed that melanoma patients who were successfully responding to immunotherapy had decreasing levels of a specific biomarker on immune cells in their blood.
While relatively few reliable biomarkers have been discovered so far, there is much work dedicated to finding new, powerful biomarkers that will enable doctors to better diagnose, treat, and monitor patients. Luckily, it appears that some have been found, and will be revealed in talks here at ASCO in the coming days. Stay tuned!