Treating Progressive Cases of Metastatic NSCLC



Mark A. Socinski, MD: Ticiana, we are now taking what we used to do in the first line, second line, and are giving it all in the first line. What do we do when they progress? I just want to talk about this real quick, because I really want to get to oligoprogression and ask Kristin to walk us through what patients are appropriately treated with—SBRT [stereotactic body radiation therapy] or other techniques—for oligoprogression. So what’s your go-to second-line regimen?

Ticiana A. Leal, MD: As a standard of care, the go-to second-line regimen is docetaxel. I think the other option would be docetaxel plus ramucirumab. For a select population, ramucirumab can be a good option. I know the REVEL study was a positive study. We saw an overall survival benefit. I think a lot of us have concerns about toxicity, and is the added survival benefit worth some of the toxicity that we saw on the trial for patients who were trial-eligible? And how does that translate to our patient population in real life?

At World Conference on Lung Cancer, we saw some studies regarding the use of docetaxel plus ramucirumab, in a subset analysis of the REVEL study, looking at rates of neutropenia and showing that, yes, the rates of neutropenia were certainly higher when you added ramucirumab to docetaxel. But the consequences of the neutropenia didn’t seem to be different between the 2 arms. There are other toxicities too that I think we still worry about. The additional thing that we saw at World Lung in 2018 was looking at whether there was any additional benefit for adding ramucirumab for a subset of patients. They identified, in this subset analysis, that for those patients who had rapidly progressive disease, some of the things that we’re talking about, adding ramucirumab….

Corey J. Langer, MD: In the frontline?

Mark A. Socinski, MD: Yes.

Ticiana A. Leal, MD: Yes. Adding ramucirumab to docetaxel seemed to be a better option for the rapidly progressive patients. Again, a subset analysis, but I thought it was interesting.

Mark A. Socinski, MD: So do people agree that docetaxel with or without ramucirumab is kind of the de facto signal?

Heather A. Wakelee, MD: Well, assuming there’s no trial, right? Because we all have so many different settings.

Mark A. Socinski, MD: Yes.

Corey J. Langer, MD: Assuming we’ve exhausted the option of additional immunotherapy. As you say, we’re adding vaccines, we’re adding other agents, immunotherapy. We want to sort of eek out the time on immunotherapy as long as possible. When it’s no longer working....

Heather A. Wakelee, MD: We do. And weekly docetaxel is much better tolerated.

Mark A. Socinski, MD: Which gets to my point. Kristin, I’m sure you see patients for whom your medical oncologists are trying to eek out that immunotherapy maintenance, right? Or some maintenance, and they have 1 lung nodule that’s growing or 1 brain metastasis or 1 liver metastasis.

Kristin Higgins, MD: Yes. So SBRT is being used frequently now for patients who have oligoprogressive disease on immunotherapy. Interestingly, the phase II data that show improved PFS [progression-free survival] with SBRT is in the de novo oligometastatic state. So for patients who typically have between 3 and 5 sites of metastatic disease, low burden stage IV disease, that’s really where the strongest data are for SBRT. And this is being evaluated in a larger study, NRG-LU002, which I encourage you to put all your patients on this trial if they’re eligible. It’s a really exciting question. Now, the oligoprogressive state is certainly something that we do in clinical practice a lot. Are there randomized data to support that approach? I would say right now, no, but it’s something that is done in clinical practice quite often and does allow for patients to stay on their immunotherapy for longer and get more time before they go to, potentially, a less effective therapy.

Mark A. Socinski, MD: Corey, your thoughts?

Corey J. Langer, MD: I agree, and I think oligo disease is really 3 different groups. For the oligo remnant metastasis, we saw a striking PFS and OS [overall survival] benefit that, frankly, I don’t think many of us truly anticipated. It caught me by surprise. And then the oligoprogression, I would guess about a third of the patients we review at our tumor board are falling into that category. We really do not have prospective studies to help define the optimal approach in that group.

Kristin Higgins, MD: Yes, and we do have some studies in the pipeline that are under development for the oligoprogressive patients. Also, unanswered questions are: What’s the optimal SBRT dose? What’s the optimal timing when SBRT should be delivered for that patient population?

Corey J. Langer, MD: There’s a third group. These are folks who’ve had definitive treatment for their either early stage or locally advanced therapy and they recur but in a limited number of locations—1 to 3, 1 to 4. They have definitive ablation of the recurrence. So whether it’s surgery, or radiation, or RFA [radiofrequency ablation], then what? There’s no right answer. There are certainly no prospective studies. But in phase II, we’ve looked at pembrolizumab in this setting and have seen a median PFS now approaching 20 months and a median survival that’s not been reached. Now, could we do as well with other agents? It’s unknown, but that’s another group for whom I think we need a prospective randomized trial.

Transcript Edited for Clarity

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