Emerging Concepts on the Role of Immunotherapy in NSCLC

Transcript:

Martin Dietrich, MD, PhD: I have another concern. This is something we’ve seen in lung cancer more than in other disease spaces: the question about management of toxicity. We’ve seen this dramatically in the CTLA4–PD-1 combinations. I’d love to hear your thoughts. The concern about the addition of CTLA4 was driven by a fear of toxicity, of the application of a second agent. You and I agree that we need a not milder but more stringent response. One of the findings that all these trials have is that the more immunotherapy toxicity we see, the more immune activation and the more we have a surrogate marker of prolonged good outcomes. Also, many of these patients who had to stop therapy due to an autoimmune adverse event [AE] have better long-term survival. How do you relay to a colleague that relying on your expert guidance about the concern of toxicity, especially in the setting of the recent approval for tremelimumab? How do you approach that in the bigger context of immunotherapy adverse events?

Meghan J. Mooradian, MD: That’s an excellent question. It’s something that we have to be aware of across disciplines, not only the treating medical oncologists but the patients’ primary care doctors. The physicians who are in the emergency department understand that these drugs are different from traditional oncological care, which was based on chemotherapy, and how timely identification of an immune-related adverse event is key with optimal management. This often will involve some degree of immunosuppression, particularly in grade 3 and 4 events. I often tell patients and colleagues that if we’re armed with knowledge about how best to identify, diagnose, and manage toxicity, that’s the key step in terms of delivering thoughtful and safe care. Though we have to be aware that as we add agents, there’s an increased rate of toxicity. That’s why we have a higher ceiling in terms of that efficacy bar.

We want to see that the addition of a fourth agent is going to add enough efficacy to overcome toxicity. That’s how oncologists are delving through this data. I’m reassured that when we’re looking at the dosing done in non–small cell lung cancer with the reduced dose of the ipilimumab, often at that 6-week interval, we’re seeing fewer grade 3, 4, and 5 AEs than when we compare it with the higher-dose ipilimumab 3 mg/kg–nivolumab 1 mg/kg that we commonly use in melanoma and renal cell [carcinoma]. The most important thing is the education of the medical field and educating our patients. If there’s something changing, [we want them] to let us know immediately. Prompt diagnosis and evaluation management are key to preventing immune-related adverse events from becoming more challenging.

Mass General is part of a large hospital, so we’re lucky to have a group of subspecialists who work with our hospital-based team to evaluate patients who are admitted and help care for them. We’ve seen that despite the overwhelming rise in the numbers of patients receiving immunotherapy over the past 5 years, the actual rate of hospitalization has stayed the same. That speaks to the fact that we’re much better at dealing with adverse events as an outpatient, working with our subspecialty colleagues in preventing the need for escalation of care. That’s happening across the board. That’s done only through thoughtful dialogue across disciplines and academia in the community.

Martin Dietrich, MD, PhD: I agree. You mentioned something earlier that’s important to highlight. Our end points in clinical trials maybe aren’t capturing the full impact. Unfortunately, even with the best of our regimens, the median—meaning 50% of patients affected—isn’t a reality. We’re moving the needle, but it’s very gradual. In long-term readouts—5 years for [CheckMate] 227, 4 years for POSEIDON—we see that the long-term survival is really improving. This is making these long-term survivals possible.

In my opinion, until we have more epitope-directed immunotherapies—even those come with their own challenges and immune toxicities—we have to accept and get better at managing these autoimmune toxicities. We learned a lot. It’s my firm belief that ipilimumab was our sparring partner in the beginning and probably caused some bad experiences along the way. For many years, despite many targets from TIGIT, LAG3, and others that have been utilized, CTLA4 has been the only 1 that has shown clinical improvement. This is an important part of thinking about a long-term strategy that may make this short-term intensified management worthwhile.

I’d like to thank you. I’m going to hand it back to you for your closing parts. I enjoyed the excellent exchange and discussion. Thank you so much for your time.

Meghan J. Mooradian, MD: Thank you. The pleasure is all mine. It’s always great to be able to take time and talk to a fellow oncologist and think through some of the new data. We’re armed with so much. It’s just a matter of how to distill it down and find the right path forward for the individual patient in our clinic. We’re all working hard to achieve that. With that, thank you for joining in this insightful discussion. Thanks to the audience for watching this OncLive® Peers & Perspectives program. We hope this was informative.

Transcript edited for clarity.