Immunotherapy Combos on Horizon, But Cost Barriers Remain

George D. Demetri, MD

Samir Khleif, MD

Combination immunotherapy could easily be on the horizon for patients, but cost effectiveness plays a major role in its implementation, according to Samir Khleif, MD.

In an interview withTargeted Oncology, Khleif, director, Georgia Cancer Center, GRU Cancer Center, discusses why despite the rapid growth of immunotherapy treatments and the potential benefit to a large patient population, these therapies need to be carefully considered due to cost.

Khleif also discusses the possible use of standard therapies in combination with newer therapies, as well as biomarker development for these treatments.

TARGETED ONCOLOGY:Can you talk about the fundamental concepts and future strategies for combining immunotherapy with radiation therapy?Khleif:Immunotherapy and immune oncology is a growing field. It has led to tremendous progress in patient care and in patient outcome. However, when we think of the current drugs that exist in the market that are really making very great impact and splash in this area, including the anti PD-1 and anti PD-L1 areas, at the end of the day they're working in 15% to 30% of patients. So 70% to 85% of patients do not respond to those drugs, and more importantly a lot of patients that respond, they recur.

How we can enhance this? The answer is combination immune therapy. One of the issues with combination immune therapy is the price of those drugs, which is pretty well-above the $50,000 to $100,000 per year, per patient. This means we have to find ways to enhance on those therapies that can be effective and can be a price that's reasonable.

One thing we have to think about is standard therapy, which can be either chemotherapy or immune therapy. We know that some chemotherapies are immune modulators, with a good example being cyclophosphamide. We know that low dose cyclophosphamide, which is a very inexpensive drug, can lead to major enhancement and major improvements in immune therapeutic outcomes.

TARGETED ONCOLOGY:: Is there a role for radiation therapy with immunotherapy?Khleif:Radiation therapy is an option. We've used radiation therapy for 70 or 80 years to treat cancer, but now we know that radiation therapy can be utilized when given on a tumor to generate not only a local effect, but a systemic effect too. That systemic effect is caused by an immune outcome, meaning that the radiation therapy is leading to a proper immune response from that local tumor within the body that leads to the response of the rest of the tumors.

Do we know how that is generated? Do we know how to give the radiation therapy? There are lots of fundamental issues that need to be answered, which is a little bit different than the standard way we've been using this for years. We need to think about it in a completely different way where we're not zooming in on that tumor to kill it. We're zooming in on that tumor to generate the proper immune response. So how we give it, what's the volume, what's the dose, ect. is important, and because it leads to changes within the microenvironment of the tumor that lead to the development of an immune response, when you think about combinations of therapies, we need to know how that radiation affected the tumor.

All of these are fundamental issues that need to be answered, and need to be addressed for the next few years so we can utilize radiation therapy as part of the immune therapeutic approach to cancer. This is also important to how we understand not only the microenvironment, but how to measure that microenvironment, and accordingly those biomarkers are going to be crucial to guide our approaches to radiation therapy to be in combination with immune therapy.

TARGETED ONCOLOGY:: What are some next steps to take to start answering these questions?Khleif:We need to understand the science, so lots of preclinical testing and animal testing needs to happen. We also need to design clinical trials based on the outcome of the immune biology that we understand in preclinical models, and we need to test the way we give radiation therapy and what kind of immune biomarkers we can develop to guide through this.

I think radiation therapy should be a part of this field, but again, we need to change the way we've been thinking about this treatment for the past 80 years and remodulate our way of approaching it to be of value for the immune therapy rather than to kill the tumor itself. We need to change our mind from taking radiation therapy concept as a local control therapy into a systemic therapy.

TARGETED ONCOLOGY: In terms of biomarker development, where do you think we are now and where do we need to go?Khleif: