Experts review data from the IMpower133 trial, supporting the use of atezolizumab plus carboplatin as the standard of care for advanced small cell lung cancer.
PUBLISHED May 16, 2019
Philippa Cheetham, M.D.: Getting down to data and information we’re using from trials, let’s talk about the IMpower133 trial and where does this fit into using evidence from trials to bring into clinical practice.
Edward Kim, M.D., FACP: Well, the IMpower133 … was published in the New England Journal of Medicine last fall and did demonstrate, in a randomized setting comparing the added atezolizumab to the carboplatin and etoposide backbone, that it was better. The triplet was better than the two drugs. There was an overall survival improvement, and we use that as a gold standard when we look at oncology trials especially. It is under priority review right now at the FDA. We are using it in practice. This is the standard of care right now for patients with extensive stage small cell cancer, unless they have specific contraindications.
Philippa Cheetham, M.D.: In terms of the benefit that was shown in this trial, if you’re looking at with and without the immunotherapy, how much benefit are we seeing in terms of survival?
Edward Kim, M.D., FACP: The medians were several months, but as we know, the ranges can be very drastic for folks. I think it’s still early with some of the data, but what we have tended to see is that the survival curves for people who are doing well, at the tail end of the curve as we call it, the people who get past the chemotherapy and then they’re on the maintenance drug, the atezolizumab afterwards, those folks are living longer. And we’re hopeful to see that that continues as we follow data from this trial longer. But I think it is vital for people to understand that is something that should be discussed with an oncologist if you are diagnosed with this disease.
Philippa Cheetham, M.D.: Of course. And if patients are being offered these treatments, can you talk briefly about the schedule, the set up for patients who are embarking on treatment with chemotherapy and immunotherapy?
Edward Kim, M.D., FACP: Yes, the different immunotherapies have different schedules. Some of them are given on a two-week basis, some of them given on a three-week basis.
Philippa Cheetham, M.D.: These are infusions as well like the chemotherapy.
Edward Kim, M.D., FACP: Yes, they’re infusions. The CARBO [carboplatin] and the etoposide stay the same. So I think most people, given the value of immunotherapy across multitudes of tumor types, are not so picky about the infusion schedule as they used to be with cytotoxic chemotherapy. But atezolizumab is one of those that’s given every four weeks. It’s convenient to give. It’s very similar to some of the other drugs out there.
Philippa Cheetham, M.D.: In terms of side effects with the immunotherapies, any that you specifically emphasize with patients in addition to the typical side effects that you’re counseling patients about with chemotherapy?
Edward Kim, M.D., FACP: Immunotherapy is funny that way in that there are some side effects that will present early and then some that will present later. So we do counsel them on both, but it’s really important for the clinician to follow these things. Early on we worry about any diarrhea, and if they have any type of diarrhea, especially bad diarrhea, we don’t want them being treated with Imodium or those aspects because this is most likely inflammation or colitis. And those need to be treated with steroids. We don’t like people taking a lot of steroids when they’re on immunotherapy because that tends to counteract the effects. But to manage side effects, we have to do it and it’s OK. They’ll come off and then we’ll be able to restart.
Later effects, we look for thyroid issues or glandular issues like with glucose levels. You can also have inflammation of any organ really, whether it’s the lungs, the eyes, the kidneys. So those are things we keep an eye out for, and as we see patients back for their visits, we’ll go through a checklist and ask them these things. But I have found them personally to be very tolerable. I’ve not seen as many side effects as, for instance, the melanoma doctors will mention. And I think the different diseases have different side effect profiles, even though it’s the same drug.
Philippa Cheetham, M.D.: Right. And you’ve talked already about many of these patients are presenting with some systemic side effects — fatigue, weight loss. Do you find that these treatments exacerbate that or do you often find that patients, when they’re responding, actually could go the other way and start to gain weight or get less fatigue? How does it play out and how do you separate side effects of cancer from side effects of treatment?
Edward Kim, M.D., FACP: I really focus on those aspects with patients. When the drugs work, then you see improvements and people feel better, they know they’re feeling better. Their appetite starts coming back. You don’t like it when you see those continued symptoms get worse and worse, despite the therapy going in. That’s usually not a good sign. But we do see dramatic changes in folks if the drugs are working and that’s beneficial.
Philippa Cheetham, M.D.: We’re giving lots of treatments to patients who aren’t in their youngest years of life. We’ve talked already about the comorbidities of other medical problems. It’s so important, isn’t it, to work with other members of our team to not only deal with the practical issues and talk about side effects of treatment and how to manage those but to address the emotional issues of going through quite challenging treatments. Let’s talk a bit about the multidisciplinary team and the role, not just of specialists like yourself, radiation oncologists, pathologists, surgeons where appropriate, what’s the role of your specialist colleagues and colleagues who are working with you to deal with issues very relevant to patients like treatment side effects?
Edward Kim, M.D., FACP: It really is quite diverse. Supportive oncology is a great service because they manage your mental being, your psychosocial being and other aspects [where] symptoms may occur. People get depressed. My wife is a psychiatrist, and she’s probably got me on medication all the time, but that’s an aside. I think people need help, and if it’s their mental sort of aspect that’s holding them back, then we need to help that. If it’s a physical aspect, then we need to also help them there. We have art therapy, we have a dog at our institute that helps with pet therapy during infusions.
Philippa Cheetham, M.D.: Probably good for the doctor as well as the patients.
Edward Kim, M.D., FACP: Yes, all of those things help quite a bit. Physician burnout is another big issue. It is very stressful, and I think you have to engage these folks. Sometimes patients don’t feel right because it’s their hormones. A thyroid hormone makes people feel weird when it’s either too high or too low. So almost every one of my patients on immunotherapy is seeing an endocrinologist in our system. We know that cardiac issues can occur with folks, especially as they start living longer, and so we have cardio-oncologists involved as well and certainly all of our integrative medicine folks. It’s good to have those departments available.
Philippa Cheetham, M.D.: We also know that not all crises, medical and emotional, happen during normal business hours, 9-5. What support systems are available when patients have a problem evening, weekend and the office is closed? You work with backup staff in the community.
Edward Kim, M.D., FACP: It’s a challenging situation whenever that happens, and of course, everyone gets sick usually on a Saturday night or a Sunday night. We try to keep in communication with our faculty because they’re obviously the cross-covering doctors. We give education to folks about side effect management in immunotherapies. We have our pathway set up so people can look and make sure that they’re doing the right thing. Because if you haven’t prescribed a lot of these, then you feel uncomfortable doing that. And we have a great supportive oncology team. We actually have a separate department in a community-based hospital that is a department of supportive oncology, and they will answer our calls 24/7 as well. So it’s really great to have that.
Philippa Cheetham, M.D.: It’s really important I think for patients to go directly to the doctors and nurses who are treating them, so that they can address their individual concerns and questions. And hopefully we’re more accessible now with email, so that patients can reach out to us about specific concerns for their own doctor.