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Treatment After Progression in Advanced-Stage NSCLC

Panelists: Benjamin P. Levy, MD, Sibley Memorial Hospital; Sanjay Popat, PhD, FRCP, Imperial College London; Solange Peters, MD, PhD, Centre Hospitalier Universitaire Vaudois; David Planchard, MD, PhD, Institut Gustave Roussy; Suresh S. Ramalingam, MD, Winship Cancer Institute
Published: Wednesday, Oct 17, 2018



Transcript:

Benjamin P. Levy, MD: I have one last question about triplet therapy. For those of us who are using it up front for our patients without an actionable mutation—I get this question a lot—what do you do next outside a clinical trial? Maybe we can spend 2 minutes on this. What are people’s perspectives, insight, on what the best options are for these patients after? You’re giving them all the active therapies, and when patients’ tumors begin to progress, we’re left with few options outside clinical trials. Off a clinical trial, because I think we all want these patients on trials, we need these questions answered. Off a clinical trial, what are the best options for these patients?

Suresh S. Ramalingam, MD: Right now, Ben, chemotherapy is what we end up offering these patients. Docetaxel, which has been salvage therapy for a long time now, continues to be the cornerstone. Now, the ramucirumab/docetaxel combination had modest survival advantage over using docetaxel alone. In a patient who is appropriate for the combination therapy, that would be an appropriate recommendation. Otherwise, use docetaxel alone. But we all agree that’s not going to give us the kind of results that our patients are looking for and what we want for our patients. We invariably have to go back and ask the question, “How can we develop more effective treatment options?”

At this meeting, there are some studies that are being reported early. This morning, we saw Matt Hellmann present the results of a small study with about 70 patients combining an HDAC inhibitor, entinostat, with pembrolizumab in patients who had progressed on immunotherapy. Now, the response rates were not great—about 10%—but disease stabilization was seen in another 50% of the patients. So that provides some suggestion that these combination approaches might result in better outcomes for this patient group.

Benjamin P. Levy, MD: Epigenetic strategies are going to make their way in.

David Planchard, MD, PhD: Don’t forget that most of these patients have maintenance therapy with an immune treatment alone now. Generally, they receive only 4 cycles with a platinum-based therapy. We should also seek to try to introduce a platinum therapy. Because some patients might receive immune treatment for 6 months, 1 year, or 2 years. And so they have a good performance status. For some of these patients, just introducing a platinum—cisplatin with another drug or carboplatin/paclitaxel weekly—might bring a huge benefit to our experiences. That’s why we might still be aggressive in these populations when they progress beyond the immune treatment arm.

Solange Peters, MD, PhD: Interestingly, there are 2 series now that will be updated early next year showing that chemotherapy after checkpoint inhibition might be of particular interest. Of course, it’s a retrospective series, but it shows that this monotherapy—vinorelbine, docetaxel, gemcitabine—would give rise to 30% or 35% or some such response rate compared with 7%. So there’s really room to give it. It’s frustrating, but rechallenge with chemotherapy, even if it’s just Taxol [paclitaxel]. We’re still not at a point where we should try to manipulate what we have. I’ve seen colleagues giving ipilimumab/nivolumab or adding bevacizumab, but I think we need data and to move into clinical trials. There’s the cytokine story, which will be presented again. There might be salvage therapy using immunotherapy that will come, but we need to document it before testing it in the patients without data.

Transcript Edited for Clarity

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Transcript:

Benjamin P. Levy, MD: I have one last question about triplet therapy. For those of us who are using it up front for our patients without an actionable mutation—I get this question a lot—what do you do next outside a clinical trial? Maybe we can spend 2 minutes on this. What are people’s perspectives, insight, on what the best options are for these patients after? You’re giving them all the active therapies, and when patients’ tumors begin to progress, we’re left with few options outside clinical trials. Off a clinical trial, because I think we all want these patients on trials, we need these questions answered. Off a clinical trial, what are the best options for these patients?

Suresh S. Ramalingam, MD: Right now, Ben, chemotherapy is what we end up offering these patients. Docetaxel, which has been salvage therapy for a long time now, continues to be the cornerstone. Now, the ramucirumab/docetaxel combination had modest survival advantage over using docetaxel alone. In a patient who is appropriate for the combination therapy, that would be an appropriate recommendation. Otherwise, use docetaxel alone. But we all agree that’s not going to give us the kind of results that our patients are looking for and what we want for our patients. We invariably have to go back and ask the question, “How can we develop more effective treatment options?”

At this meeting, there are some studies that are being reported early. This morning, we saw Matt Hellmann present the results of a small study with about 70 patients combining an HDAC inhibitor, entinostat, with pembrolizumab in patients who had progressed on immunotherapy. Now, the response rates were not great—about 10%—but disease stabilization was seen in another 50% of the patients. So that provides some suggestion that these combination approaches might result in better outcomes for this patient group.

Benjamin P. Levy, MD: Epigenetic strategies are going to make their way in.

David Planchard, MD, PhD: Don’t forget that most of these patients have maintenance therapy with an immune treatment alone now. Generally, they receive only 4 cycles with a platinum-based therapy. We should also seek to try to introduce a platinum therapy. Because some patients might receive immune treatment for 6 months, 1 year, or 2 years. And so they have a good performance status. For some of these patients, just introducing a platinum—cisplatin with another drug or carboplatin/paclitaxel weekly—might bring a huge benefit to our experiences. That’s why we might still be aggressive in these populations when they progress beyond the immune treatment arm.

Solange Peters, MD, PhD: Interestingly, there are 2 series now that will be updated early next year showing that chemotherapy after checkpoint inhibition might be of particular interest. Of course, it’s a retrospective series, but it shows that this monotherapy—vinorelbine, docetaxel, gemcitabine—would give rise to 30% or 35% or some such response rate compared with 7%. So there’s really room to give it. It’s frustrating, but rechallenge with chemotherapy, even if it’s just Taxol [paclitaxel]. We’re still not at a point where we should try to manipulate what we have. I’ve seen colleagues giving ipilimumab/nivolumab or adding bevacizumab, but I think we need data and to move into clinical trials. There’s the cytokine story, which will be presented again. There might be salvage therapy using immunotherapy that will come, but we need to document it before testing it in the patients without data.

Transcript Edited for Clarity
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Online CME Activities
TitleExpiration DateCME Credits
Community Practice Connections™: Oncology Best Practice™ Decision Points in Advanced NSCLC: Assessing Treatment Options Beyond Disease ProgressionNov 30, 20181.0
Community Practice Connections™: Precision Medicine for Community Oncologists: Assessing the Role of Tumor-Testing Technologies in Cancer CareNov 30, 20181.0
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