Round 2: Managing Oligoprogression

The discussion turns to oligoprogression in the second round, with panelists debating the role of local radiotherapy, continuation of immunotherapy, and potential synergy with TTFields therapy. Key considerations include site selection, multidisciplinary input, and feasibility of treatment options. 

To hear arguments related to the optimal approach for patients with nNSCLC, see Round 1.

To hear arguments related to sequencing in the real-world setting, see Round 3.

Beth Sandy: Let's move on and talk about this scenario, which I think this scenario we see more and more often these days. And we really, in my practice particularly, we have really looked to have been more aggressive in managing oligoprogression. So, the question here is: Should you treat oligoprogression with local consolidative radiotherapy, Tumor Treating Fields, both, or switch systemic therapy?  

Okay, so Dr Chun—and do me a favor, start off with: What do you consider oligoprogression? I think we had a study one time, I swear it said there was 6 sites, right, Corey? I was like, “oligo” in my mind means “1,” but what does oligoprogression mean to you?

Dr Stephen Chun: So that's a great question, and unfortunately, I think it is something that is in the eyes of the beholder. In clinical trials like NRG-LU002, Puneeth lynegar’s trial, looking at oligometastatic consolidation, looking at SABR-COMET, looking at a number of these trials, the arbitrary number was set at maximum 5 sites. This really didn't come from, “Okay, 5 versus 6,” or something like that. It’s really, we evolved on this planet with 5 fingers, and if we evolved on a planet with 3 fingers, it would have been 3. That's the truth, right?

Beth Sandy: So that’s it. 

Dr Stephen Chun: The same thing is true with esophageal cancer. Historically, radiation was 5 centimeters above and below the tumor, and people were like, “Oh, did that come from surgical series? Did that come…” and Bruce Minsky said, “No, I’ve got 5 fingers and a 5-millimeter PTV set up in radiation.” We do a lot of this in medicine, where we pick a number—5, 10—because it's a nice number.  

In any case, I call it as I see it. If I see 1 or 2, 3 oligometastatic locations that are favorable—and I do think when you get to 5, 6, 7, that's not really oligometastatic anymore—but I think there’s two things: number of sites (generally less than 5) but also location. 

For example, there are metastases that even if I see 1, I don't really believe it's oligometastatic; peritoneal carcinomatosis, and I see 1 peritoneal metastasis. I do not believe that is oligometastatic. That is not oligometastatic. 

Similarly, it also depends on the disease site. If I see lung metastases from a prostate cancer, do I really believe that's oligometastatic, either? So, there’s a lot of nuances there.  

Two things: number of sites, generally less than 5, but also locations that are amenable to local consolidative therapy. Not small bowel metastases, not peritoneal carcinomatosis. Let's say you have 1 metastasis, but it’s comprising the entire length of the femur. I don't really believe that's oligometastatic either, because it's marrow involvement, it's a huge length of bone. 

So I don't know if that answers your question or creates more questions.

Beth Sandy: I just wanted to get at your opinion. So what would you do in this situation here, managing oligoprogression in this patient?

Dr Stephen Chun: So I get referred a large number of these patients because 80% of patients on maintenance IO are eventually going to progress, and I get the sense that medical oncology is not particularly enthusiastic about switching systemic therapy, especially if it's 1 or 2 or 3 or something lesions that are progressing. I offer local consolidative radiation if it's feasible, and I send an email to my medical oncology colleagues. I say: By the way, yeah, we're going outside of where there’s really strong evidence for radiation in this setting. I remind people, LU002 was negative, but we empirically offer this because LU002 was all comers. It was de novo oligometastatic disease.  

So that's the other thing, oligometastatic disease hasn't been particularly well-defined. I think of de novo oligometastatic disease, meaning upfront, they presented with oligometastatic disease, which I think is different from induced oligometastatic disease.  

Let's say you have massive systemic disease, it is consolidated to oligometastatic disease, which is different from oligoprogression. And LU002 included all of the above. I think there is a very open question at this point, which they are trying to answer with the CURB Trial, on is there is a role for radiation and oligoprogression, purely progression. There is also the ALLIANCE-A021, Steve Shield’s study, trying to look at this.  

But I'm happy to offer it, especially if it's something I can do safely, because patients don't want to switch systemic therapy, especially to something that's going to be toxic.  

They usually always are going to prefer this to docetaxel or whatever else. And I say to my medical oncology colleagues, “By the way, I'm offering this without level 1 evidence. On that note, there is level 1 evidence for Tumor Treating Fields. Would you like me to offer them this, too?” And I've never had them say no yet because they're already coming to me wanting, obviously, to keep them on immune therapy, because the patient's doing well on it. And that's been how I've incorporated Tumor Treating Fields into my practice.  

Beth Sandy: Dr Patel?

Dr Eshan Patel: I think oligoprogression, as Stephen mentioned, I think it’s really site matters, size matters. Really, how many different sites, we need to balance out the risk and benefit of radiation also, right?  

But I'm a big opponent in terms of oligo mets to be treated locally with consolidative radiation therapy and continue immunotherapy, as we can. There was a small study, a retrospective study, but patients who had oligomets did get local control therapy; it could have been even surgery if it was 1 or 2 lesions that could be resected, versus consolidative radiation therapy, and patients continued on immunotherapy. And I think 2-year survival was still very high, 80%, 90%.  

I will definitely like to continue and get the maximum mileage out of immunotherapy, especially if there are patients who had a good clinical response for a longer period of time or patients who are high PD-L1, high TMB, or some other marker that supports that this patient will continue to have a response from immunotherapy. So I will like to get radiation, I would like to continue the immunotherapy, and definitely add at that time, Tumor Treating Field.  

I think the Tumor Treating Field, the mechanism of action, the way it causes apoptosis in the cell, and then that causes the tumor to be a “hot tumor” environment by releasing a lot of those cytokines and inflammatory markers. I think that's very important for T-cells’ infiltration and better T-cell surveillance throughout the body. It really enhances the immunotherapy at that time.  

And technically, if the patient had progression after platinum-based chemotherapy, so they meet the criteria to go on the Tumor Treating Field, right? So, the patient will get local control, whatever that new clone that led to the progression, you knock that out by radiation therapy, and you continue your immunotherapy. And I would add to Tumor Treating Field to enhance my therapy at that time.  

Beth Sandy: Because you feel like that's enhancing the immunotherapy effect. 

Dr Eshan Patel: Correct.