David S. Ettinger MD, FACP, FCCP has served on the ICLIO Advisory Board since its inception. Recently we spoke with Dr. Ettinger about his role in immuno-oncology (I-O) advocacy and his vision for ICLIO. Dr. Ettinger is the Alex Grass Professor in Oncology and Professor of Oncology, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Medicine, Baltimore. He has been at the heart of National Comprehensive Cancer Network (NCCN) guideline development for two decades.
Raising Awareness About I-O
Please describe your current role in ICLIO and how you’re involved with its programs.
Dr. Ettinger: I’m on the ICLIO Advisory Committee, and I’m also in charge of the Lung Subcommittee, since my interest is lung cancer. I also chair the NCCN panel on non-small cell lung cancer, which I’ve been doing since 1996. Before I talk about my role, let’s talk about ICLIO and the Association of Community Cancer Centers (ACCC).
I think it’s most impressive that ACCC and its staff are doing what they’re doing with the Institute for Clinical Immuno-Oncology, which is, of course, supported by a charitable donation from Bristol-Myers Squibb and an educational grant from Merck & Co. The goal is to inform, teach, and educate nurses, doctors, nurse practitioners, pharmacists, urgent care centers, emergency room staff, and clinicians that are involved in seeing patients who receive immunotherapy—especially with regard to toxicities.
The whole idea is to [also] educate rheumatologists, pulmonologists, nephrologists, gastroenterologists, because for any “itis” that patients can develop, someone has to be involved or understand the immune toxicity secondary to immunotherapy. That’s very critical. The ICLIO program has already had 29 e-newsletters looking at managing toxicities, case studies, what’s available in I-O clinical trials, as well as webinars on topics such as reflex testing, adverse events, specific issues relating to lung cancer, melanoma and other diseases, including Merkel cell carcinoma and renal cell carcinoma. Down the road, every disease is probably going to have immunotherapy and we’ll need to be able to identify which patients would benefit from it.
So, what I’ve been doing in my ICLIO committee roles is talking about toxicities and involving junior [Hopkins] faculty, like Jarushka Naidoo MBBCh, in talking about toxicities. That’s one of our interests. One of my research nurses, Joanne Riemer RN, also talks about immunotherapy toxicities, and has developed a brochure that’s been used in many presentations.
ICLIO Visiting Experts Workshop
What is unique about ICLIO, which I think is phenomenal, is programs like the ICLIO Visiting Experts, in which community hospitals can host a workshop with a visiting expert in I-O to help them develop their own I-O program. Most doctors, unless they’re in a big practice, are somewhat unaware of I-O management best practices.
I’ve been impressed to discover what my ICLIO committee colleagues are doing in the community. For instance, (ACCC Immediate Past President) Jennie Crews MD, MMM, FACP, is based in Washington state and has a program in immunotherapy. [Editorial note: Dr. Crews now serves as the Medical Director of the Seattle Cancer Care Alliance Network and Research Integration and Associate Professor of Medicine at the University of Washington.] It’s impressive what’s been going on in a short period of time and how many people have stepped up to really get moving on I-O, because in the end, we’re talking about patient- and family-centered care, and this all revolves around patients and their families. It’s a credit to ICLIO and the other members of the Advisory Committee who are doing the work to make this happen.
Quality Care, Close to Home
And in the end, who is I-O treatment going to benefit? It’s going to benefit the patients and enhance the ability of the doctors treating those patients. Is it easy? I don’t think so. Where I am in Baltimore, we have a lot of urgent care centers, the emergency room is busy, and you want to give providers enough knowledge that if they get a patient there with immunotherapy, they know what to do or know where to refer. I’m a specialist in lung cancer; however, when I was young I did head and neck, I did gynecology, and I can tell you I don’t know how the generalist in oncology does it today with all the things that individual has to know to take care of the patient. I’m amazed.
What would you say the impact of ICLIO’s programs has been on the way that oncology or immuno-oncology is practiced in the community?
Dr. Ettinger: I think it’s improving the way the community doctors are treating patients with immunotherapy, and part of it really relates to the size of the practice. We’re at a time when more and more hospitals are buying practices, and we’re also at a time when insurance companies are buying health systems. We have a problem in which in a lot of areas with small practices and communities, there is no choice but to send patients to a big hospital several hours away. Unfortunately, a lot of the areas of small practice there’s no choice, because the communities are small and there’s no other way to do it, unless you’re sending the patient to a big hospital several hours away. If you can get good quality care closer to home and be with family, that’s the way, in my opinion, it should be done.
But ICLIO is making a good start in getting a lot of people involved., and I think what’s happening is that doctors in the community are making contacts. They’re not afraid to call on experts. I speak to a lot of physicians in my area in a five-state region who call asking for advice, or they even have a patient come up here [to Baltimore]. When I ask the patient, “When your doctor said you’re coming up here, what did he say?” “Oh, David’s a friend. I’d like to get his opinion.” I said, “You can have the best of both worlds. You can get an opinion from a super subspecialist and get treated closer to home.” That’s perfect, that’s the way you really want to do it.
Do I see patients from thousands of miles away from overseas that want to get treated here? Yes. But are they away from family? A lot of times. Is that good? No. So I think down the road, and we’ve talked about even global teaching of immuno-oncology. Everybody can learn no matter where they are. I can assure you I have junior colleagues that are doing so much in immuno-oncology, they know more than me. Do I feel embarrassed? I don’t feel embarrassed. I want to learn as well.
Ongoing Clinical and Non-Clinical Challenges
What do you see as the main clinical and non-clinical challenges that really have to be tackled in the next two to five years?
Dr. Ettinger: Non-clinically is going to be reimbursement. That is going to be key, in my opinion. And, you know, when 62% of all the bankruptcies in this country are due to healthcare, we have a problem. There has to be a shared responsibility. Put it this way. Doctors are being asked now by hospitals to share the risk. It seems to me the pharmaceutical industry has to do the same thing. Share the risk. In other words, it’s one thing if you’re going to get a drug that has a 60%, 70% response rate and it’s going to cost. It’s another thing if you’re going to get a drug, say an immunologic drug, that has a 15% response rate and that’s about $11,000 every two to three weeks.
It seems to me the pharmaceutical industry should be sharing the risk. For instance, give the patient a drug for nothing for the first two cycles, and if they’re responding, then one can charge. Is that being done in other countries? It is. It is actually being done with other drugs, maybe not just in oncology. We pay more for drugs than anybody in the world, and that is a different issue. It seems to me the Food and Drug Administration (FDA) has to be given the right to ask about price, because if it doesn’t happen, you know as well as I that there are companies that tell practices what they should charge.
When metastatic cancer is treated by radiation, localized therapy may shrink not only the tumor being directly treated, but also more distant tumors. This abscopal effect occurs due to the migration of irradiated tissues into the circulation; the passage of unexposed lymphocytes through irradiated tissues; and the release of humoral factors and microvesicles shed from the plasma membrane of irradiated cells.
Clinically, you’re going to see many combinations of not only ipilimumab and nivolumab, but also combinations with chemotherapy or targeted therapy, and we know that people are looking at combining checkpoint inhibitors with radiation oncology, looking for an abscopal effect. My institution partnered with Memorial Sloan Kettering to study I-O before surgery and we’re seeing some dramatic responses;1 so maybe neoadjuvant I-O therapy is going to happen too. We also already know that clinicians need to know something about mutation load, because if patients have a mutation load, they have a better chance of responding.
All those things we have to work on in the lab and in clinical trials to come to some better handle on can we pick the right patient to get the right drug. And we already know that combinations are a little more toxic than single agent. And so, you might see oral immunotherapy down the road. That would be phenomenal because then you can start giving oral therapy and rotate it, and rotate the drugs in some fashion. I think it’s exciting times.
- Chaft JE, Forde PM, Smith KN, et al. Neoadjuvant nivolumab in early-stage, resectable non-small cell lung cancers. J Clin Oncol 35, 2017 (suppl; abstr 8508).
- Basch E, Deal AM, Kris MG, et al. Symptom monitoring with patient-reported outcomes during routine cancer treatment: A randomized controlled trial. J Clin Oncol. 2016;34(6):557-565.
- Basch EM, Deal AM, Dueck AC, et al. Overall survival results of a randomized trial assessing patient-reported outcomes for symptom monitoring during routine cancer treatment. J Clin Oncol 35, 2017 (suppl; abstr LBA2).