Opinion
Video
Benefits of Combination Therapy in mNSCLC
Specialists engage in a conversation regarding the treatment duration and the effectiveness of the current two-year approach.
Mark Socinski, MD: So in the past couple of years, we’ve seen approval of immunotherapy in early-stage non–small cell [lung cancer] [NSCLC] either as neoadjuvant perioperative or adjuvant approaches. Let’s say a patient gets that exposure. Obviously, they are very different in terms of their duration of exposure, but at some point down the road, they [experience] relapse. What are your thoughts about that population? It’s pretty much a data-free zone right now, but what are your thoughts about that? What would you do?
Martin Dietrich, MD, PhD: Well, it depends on the situation of time to relapse. Those are going to [need] a little refinement. You’re mentioning the duration of treatment. That’s one of the hottest questions in the in the early-stage setting. If I compare the now 5 regimens that have been utilized in the preoperative and perioperative setting, it looks like the 3 cycles of immunotherapy seem to be doing the majority of the work. I find this highly surprising how well this turns out. It is about a 20% improvement in event-free survival. So teasing out a very similar population that would be beneficial in the relapse setting…in general terms, we’re going to be moving from adjuvant applications to neoadjuvant applications. The data are much more persuasive, leaning on some of the other neoadjuvant vs adjuvant trials for melanoma, for example. The hazard ratios there were favoring neoadjuvant approaches [at] a level of 0.5. And it’s very plausible if a tumor microenvironment where T cells and tumor cells interact is present that immunotherapy in our checkpoint world is useful if a patient [experiences] relapses at 2 months after stopping immunotherapy. I’m not sure that I would feel compelled [that] immunotherapy is going to be using a new approach that would lead to a long-term positive outcome. So [it’s] a very challenging patient population. If somebody [experiences] relapse 2 or 3 years later, which would be down the line, I would reinitiate an approach that has a PD-1 axis in the center.
Mark Socinski, MD: Hopefully we’ll have data moving forward. You brought up the issue of duration in one of the things that we’ve accepted as standard of care based on [findings from] the original clinical trials in the metastatic stage IV setting. We give 2 years. Sometimes that’s too much. Sometimes patients think it’s not enough, and they want to go on. I’ve been consistent with stopping at 2 years, assuming…I’m convinced the disease is under very good control, and we now have some data on that population that many of them are still progression free 3 years later at the 5-year point. So it’s OK to do that, and there is a reinduction response. But what are your thoughts about duration? I know our colleagues [who manage] melanoma give shorter durations, right?
Martin Dietrich, MD, PhD: Well, [there are a] number of factors for assessment: the depth of response, both anatomic and PET [positron emission tomography]-CT in other specialties, biochemical assessments. We’ll use MRD [minimal residual disease] for assessments of viability in the future as well. Two years is the accepted number based on the clinical trial protocols, and it doesn’t seem to be a collective overall survival improvement for treating longer. Certainly, we will get responses shorter. The crux is that we don’t have any stop trials that look at criteria that would be prospectively understanding the exact need for how much immunotherapy is needed. We’ll probably be using 2 years for the foreseeable future in the metastatic setting. In the neoadjuvant setting so far, I haven’t seen a regimen in the perioperative space where the data are convincingly better than [data from the] CheckMate 816 [trial]. But there are young trials where we don’t have the full readout. There’s not any other space I’m aware of where a couple of cycles would be deemed sufficient. A lot of us will lean on some adjuvant treatment, especially if no PCR [polymerase chain reaction] is achieved. The depth of response there, both anatomically and radiographic, makes a big difference.
Transcript is AI generated and edited for clarity and readability.
