Most patients with cancer have likely heard of the term “personalized medicine” or “precision medicine,” but many are not sure how this relates to their experience with cancer therapy. We asked Ross Maclean, MD, PhD, Senior Vice President, Head of Medical at Precision Health Economics, Princeton, NJ, to explain why personalized medicine is relevant to patients with cancer and to their caregivers.
Q: Can you explain what personalized medicine is?
Dr. Maclean: Personalized medicine has 3 critical elements. The first is the scientific basis for disease at the level of the cancer cell; that is, our rapidly expanding knowledge of the many different subtypes of a single disease and how each subtype may respond to different treatments.
The second element is that the evidence for the benefits of different treatments is described in a clear and friendly manner. Because there are so many different types of cancers, and so many treatments, the doctor, and the patient often struggle to process the information. Before we can personalize medicine, we need to understand how different treatment options compare to one another. However, very few clinical trials directly compare one cancer treatment versus another.
However, a type of “evidence synthesis” (aka “meta-analysis”) is when we indirectly compare treatments by using statistical techniques; this allows patients and doctors to gain a clearer understanding of how one treatment compares with another treatment.
The third foundation of personalized medicine is shared decision-making, when the provider and the patient make decisions together about screening, diagnosis, treatment, and follow-up that are in the best interests of the patient, the family, and within the available healthcare resources.
These 3 foundations define personalized medicine, which is medicine informed by the genetic profile and the genetic characteristics of the patient and cancer that the patient is dealing with. Understanding the tumor, the patient, how that tumor will likely respond to the different treatments, and having the patient make decisions with full transparency and knowledge, is personalized medicine. It is not simply doing a fancy genetics test and expecting to get all the answers.
Q: How is personalized medicine in cancer different from other types of medicines?
Dr. Maclean: Based on my previous comments, it’s easy to think that personalized medicine is somehow new, which is not the case. But we have new technologies that take personalized medicine to a new level.
The patient-doctor interaction has been personalized for thousands of years. Some doctors are better at it than others, the nursing profession is widely acknowledged as masterful at personal patient interaction, and some patients are more engaged than others. The ability to synthesize the evidence that has been with us now for 20 to 30 years has really advanced in the past 10 years.
There’s been a major push across the West and the developed world to advance the ability of physicians and other providers to talk to their patients. There have also been major advances in the methods behind evidence synthesis. Perhaps one of the biggest advances has been in the ability to decode the human genome, and to apply that science to cancer.
Instead of chemotherapy, we now have medicines that target different tumors based on the likely response of that tumor to a specific targeted treatment—most recently, immunotherapy is triggering the patient’s own immune system to fight the cancer.
When I think about how personalized medicine differs from other types of medicine, specifically for cancer, I think it is in building off the legacy of shared decision-making, having a robust discussion with the patient. It is advancing with the novel methods for evidence synthesis, the novel treatments, and the ability to bring those together to truly focus on what therapy is likely to work best in the individual patient.
Q: Can you give some specific examples of immunotherapies as personalized medicine in oncology?
Dr. Maclean: Let’s focus on 2 examples. The first example is in malignant melanoma. As recently as 7 or 8 years ago, before the arrival of immunotherapies, malignant melanoma was treated with surgery, radiotherapy, and/or chemotherapy, and the results were fairly shocking; for some malignant melanoma tumors, up to 90% of the patients died within 9 months of diagnosis.
Now, with the arrival of immunotherapies, we have seen a stunning transformation in the response of many, but not all, tumors, to these new treatments. Today, combination immunotherapies are further transforming the results. Many patients with melanoma have now been alive for as long as 10 years after diagnosis versus the 90% mortality rate mentioned earlier.
The challenge, of course, is that not all patients with melanoma respond to immunotherapies. So how can we identify upfront those patients who will respond? That’s where personalized medicine comes in.
The second example of using personalized medicine is in lung cancer. Two novel immunotherapies include Keytruda (pembrolizumab) and Opdivo (nivolumab). Evidence indicates that some patients with lung cancer respond better and for a longer time to these immunotherapies versus other patients, and this difference in treatment response has been attributed to their PD-1/PD-L1 status. Again, identifying clinical and genetic characteristics (called “biomarkers”) of a tumor is part of personalized medicine.
The highly specific targeting of treatment based on a patient’s genetic and clinical profile, with the objective of optimizing the likely benefit and value, is also sometimes called “precision medicine.”
We are at the cutting edge of understanding how certain biomarkers are predictive of the likelihood and the depth of a patient’s response to treatment.
Q: How is personalized medicine helping all cancer patients rather than just those who have a specific biomarker?
Dr. Maclean: Well, 20 or 30 years ago, we used the word cancer in a very crude, simple way—people had lung cancer, or colon cancer, women had breast cancer. As science advances, we are learning that there are many subtypes of cancer. Different patients often have different variants of a cancer type. These tumors are clever in how they advance, and how they survive the onslaught of chemotherapy, radiotherapy, and even immunotherapy.
To go back to the PD-1 example, we are now finding that there are multiple subtypes of the same cancer, some of which respond better to treatment A, treatment B, or to a combination of treatment A plus B.
Q: What is important for patients to know about personalized medicine?
Dr. Maclean: Patients should know that the era of personalized medicine is changing very quickly. As I stated above, increasingly patients are becoming actively engaged in their care; they can gather information, ask probing questions, and expect their healthcare providers—the oncologist, nurse, physician assistant, or a primary care doctor—to talk to them in a peer-to-peer manner about how to manage their cancer, and how to manage their comorbid conditions. Personalized medicine is about caring for the whole patient, not just treating the tumor.
Q: What should patients ask their doctors and nurses about personalized medicine?
Dr. Maclean: This is not just that this drug has 3 side effects and the other drug has 2 side effects. That’s the easy bit. Rather, what patients should be asking is, “As I start finding out what’s wrong with me, how do I manage that tsunami of information?” Personalized medicine takes it to a whole different level.
It’s all very well for doctors and nurses to know where to find information, but how do you guide a patient who’s just been told he or she has cancer? How should patients ask questions about the long-term outlook, their ability to return to an active life and enjoy what matters to them, and the financial aspects of their care?
Q: What can caregivers and family members do in relation to precision medicine?
Dr. Maclean: First, family members and caregivers need to recognize that there is more to cancer care than advanced surgery, radiotherapy, or chemotherapy. It is the holistic well-being of the patient, including caring for the patient’s nutritional needs, spiritual needs, and emotional needs. Patients’ emotional and mental health needs are as important a part in overcoming cancer as are the receipt of and adherence to a cancer regimen, and the caregivers’ role is critical in that.
Second, the rule for caregivers and family members is to travel the journey with the patient. Caregivers and family members can help patients understand the differences related to treatment options.
And there are patients for whom aggressive treatment is not appropriate. Although we like to believe that if we throw enough medical technology at a problem we can cure everybody, this is not always the case. There is a time to stop treatment, to step back, and enjoy the quality of life that remains for the patient, not the quantity of life.
Patients, their caregivers, family members, and the community have an important role in personalizing a holistic approach to patients during their cancer care journey.