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Locally Advanced NSCLC: Approaching the PACIFIC Trial

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: Monday, Oct 15, 2018



Transcript: 

Benjamin P. Levy, MD: Hello, and thank you for joining us for this OncLive® Peer Exchange®. We are experiencing unprecedented progress in treating advanced non–small cell lung cancer, as the rapid development of novel targeted and immuno-oncology agents continues to transform the landscape of therapy.

In this OncLive Peer Exchange® discussion, “Clinical Perspectives on New Data in Advanced NSCLC: A Review of Abstracts from the 2018 World Conference on Lung Cancer,” I am joined by an international panel of experts in thoracic oncology. Today we will cover several important studies being presented at this year’s meeting and share insight on the implications for your clinical practice.

I’m Dr. Benjamin Levy. I’m an assistant professor of oncology and clinical director of medical oncology at the Johns Hopkins Sidney Kimmel Cancer Center at Sibley Memorial Hospital in Washington, DC. Participating today on our distinguished panel are Dr. Solange Peters, head of medical oncology at the Lausanne University Hospital; Dr. David Planchard, an associate professor of medicine and the head of the Thoracic Cancer Group at the Gustave Roussy in Villejuif, France; Dr. Sanjay Popat, a consultant thoracic medical oncologist at the Royal Marsden Hospital and reader in cancer medicine at Imperial College in London, England; and Dr. Suresh Ramalingam, professor of hematology and medical oncology at the Winship Cancer Institute of Emory University in Atlanta, Georgia. Thank you so much for joining us. Let’s begin.

We’ll start out in the stage III space, the locally advanced non–small cell cancer space, a space where we’ve really been begging for new therapies for quite a while. Of course, immunotherapy first landed in the advanced-stage setting in the second line, but it’s now being moved up to the first line. Now we’re seeing emerging data with the use of immunotherapy in the locally advanced setting, specifically with the PACIFIC trial and the use of durvalumab. Solange, do you want to take us through a high-level overview of the PACIFIC trial that was recently published in the New England Journal of Medicine? Now we have some updates here at the World Conference on Lung Cancer that continue to alter the treatment landscape for these patients.

Solange Peters, MD, PhD: Absolutely. I think the data that we have been seeing, that we will be seeing during this meeting and discussing together, confirmed the benefit of this strategy in stage III disease. I agree with you. We’ve been trying things: various chemotherapies, various radiotherapies, and some vaccines. We’ve been trying many things in stage III disease without any advancements. Now we have this PACIFIC trial, quite a simple trial, but a real-life trial. This is about patients who received radiotherapy and chemotherapy concurrently with 50 Gy and 2 cycles of chemotherapy, so it was a minimal denominator of the regimen. These patients, once they completed this induction treatment—standard of care treatment, I would even say—were randomized between placebo, the usual way to treat, or durvalumab for a year.

The first publication in the New England Journal of Medicine showed an unprecedented benefit of almost 11 months of PFS [progression-free survival], reaching 17 months, something that we are not used to observing in non–small cell lung cancer. There was a gap between the observation arm and the experimental arm, which was absolutely amazing.

The shape of the curve was very attractive, but of course the main criticism of this trial was that in the curative setting your aim is to cure the patients: What you need to show is a difference in overall survival. It’s probably also a good way think in the adjuvant trials. At this meeting, that’s what will be presented, the overall survival. What is very interesting is the fact that it confirms the overall survival is strongly positive as compared to the standard arm to the observation.

Based on that, I think we have the final confirmation that there’s something there. I would even say the magnitude of benefit is showing that there’s something interesting in trying to combine various modalities. Maybe it’s about radiotherapy. Think about the immunogenic cell deaths. You create an environment very prone to be responsive to immunotherapy, maybe. But there’s something we need to grab here in really multimodal treatment modalities in terms of gaining cure, or at least survival time, for these patients.

It’s very important to stress a last element, which will be important in Europe. In many of these patients, no tissue was available. It’s stage III disease, so it’s difficult to have enough tissue to really assess biomarkers. This result has been, I would say, provided to all-comers with non–small cell lung cancer, and the ITT [intention-to-treat] population is positive for survival.

If you look at subgroups, you face a problem of potentially not having good data in trying to differentiate subgroups. I know it’s going to be a matter of debate about PD-L1 [programmed death-ligand 1] and accessibility of tissue, but basically this trial was aiming at looking at a simple question: In an ITT population, is survival better or not? And the answer is yes.

Benjamin P. Levy, MD: I think we got definitive answers. I think all of us can agree, these are pretty impressive results. I also think there’s something that we forget. I think there were some concerns about toxicity, the layering of immunotherapy right after radiation, and if would we see pneumonitis or any other immune-related adverse events. We didn’t see that in this trial.

Solange Peters, MD, PhD: No excess toxicity. You have to know that when you give radio-chemotherapies, there’s a certain number of radiation-use pneumonitis cases. When you give immunotherapy, it happens sometimes that you have immune-related pneumonitis. But the risk was to imagine that those phenomena would increase or give rise to an excess of lung toxicity, and it’s not the case. It’s not the case in most of the trials where we try to combine radiation on the lung and immunotherapy. Decidedly, the mechanisms behind them are not cumulative or not synergistic. It’s just a fact that sometimes, radiation gives rise to some pneumonitis.

Transcript Edited for Clarity 

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Transcript: 

Benjamin P. Levy, MD: Hello, and thank you for joining us for this OncLive® Peer Exchange®. We are experiencing unprecedented progress in treating advanced non–small cell lung cancer, as the rapid development of novel targeted and immuno-oncology agents continues to transform the landscape of therapy.

In this OncLive Peer Exchange® discussion, “Clinical Perspectives on New Data in Advanced NSCLC: A Review of Abstracts from the 2018 World Conference on Lung Cancer,” I am joined by an international panel of experts in thoracic oncology. Today we will cover several important studies being presented at this year’s meeting and share insight on the implications for your clinical practice.

I’m Dr. Benjamin Levy. I’m an assistant professor of oncology and clinical director of medical oncology at the Johns Hopkins Sidney Kimmel Cancer Center at Sibley Memorial Hospital in Washington, DC. Participating today on our distinguished panel are Dr. Solange Peters, head of medical oncology at the Lausanne University Hospital; Dr. David Planchard, an associate professor of medicine and the head of the Thoracic Cancer Group at the Gustave Roussy in Villejuif, France; Dr. Sanjay Popat, a consultant thoracic medical oncologist at the Royal Marsden Hospital and reader in cancer medicine at Imperial College in London, England; and Dr. Suresh Ramalingam, professor of hematology and medical oncology at the Winship Cancer Institute of Emory University in Atlanta, Georgia. Thank you so much for joining us. Let’s begin.

We’ll start out in the stage III space, the locally advanced non–small cell cancer space, a space where we’ve really been begging for new therapies for quite a while. Of course, immunotherapy first landed in the advanced-stage setting in the second line, but it’s now being moved up to the first line. Now we’re seeing emerging data with the use of immunotherapy in the locally advanced setting, specifically with the PACIFIC trial and the use of durvalumab. Solange, do you want to take us through a high-level overview of the PACIFIC trial that was recently published in the New England Journal of Medicine? Now we have some updates here at the World Conference on Lung Cancer that continue to alter the treatment landscape for these patients.

Solange Peters, MD, PhD: Absolutely. I think the data that we have been seeing, that we will be seeing during this meeting and discussing together, confirmed the benefit of this strategy in stage III disease. I agree with you. We’ve been trying things: various chemotherapies, various radiotherapies, and some vaccines. We’ve been trying many things in stage III disease without any advancements. Now we have this PACIFIC trial, quite a simple trial, but a real-life trial. This is about patients who received radiotherapy and chemotherapy concurrently with 50 Gy and 2 cycles of chemotherapy, so it was a minimal denominator of the regimen. These patients, once they completed this induction treatment—standard of care treatment, I would even say—were randomized between placebo, the usual way to treat, or durvalumab for a year.

The first publication in the New England Journal of Medicine showed an unprecedented benefit of almost 11 months of PFS [progression-free survival], reaching 17 months, something that we are not used to observing in non–small cell lung cancer. There was a gap between the observation arm and the experimental arm, which was absolutely amazing.

The shape of the curve was very attractive, but of course the main criticism of this trial was that in the curative setting your aim is to cure the patients: What you need to show is a difference in overall survival. It’s probably also a good way think in the adjuvant trials. At this meeting, that’s what will be presented, the overall survival. What is very interesting is the fact that it confirms the overall survival is strongly positive as compared to the standard arm to the observation.

Based on that, I think we have the final confirmation that there’s something there. I would even say the magnitude of benefit is showing that there’s something interesting in trying to combine various modalities. Maybe it’s about radiotherapy. Think about the immunogenic cell deaths. You create an environment very prone to be responsive to immunotherapy, maybe. But there’s something we need to grab here in really multimodal treatment modalities in terms of gaining cure, or at least survival time, for these patients.

It’s very important to stress a last element, which will be important in Europe. In many of these patients, no tissue was available. It’s stage III disease, so it’s difficult to have enough tissue to really assess biomarkers. This result has been, I would say, provided to all-comers with non–small cell lung cancer, and the ITT [intention-to-treat] population is positive for survival.

If you look at subgroups, you face a problem of potentially not having good data in trying to differentiate subgroups. I know it’s going to be a matter of debate about PD-L1 [programmed death-ligand 1] and accessibility of tissue, but basically this trial was aiming at looking at a simple question: In an ITT population, is survival better or not? And the answer is yes.

Benjamin P. Levy, MD: I think we got definitive answers. I think all of us can agree, these are pretty impressive results. I also think there’s something that we forget. I think there were some concerns about toxicity, the layering of immunotherapy right after radiation, and if would we see pneumonitis or any other immune-related adverse events. We didn’t see that in this trial.

Solange Peters, MD, PhD: No excess toxicity. You have to know that when you give radio-chemotherapies, there’s a certain number of radiation-use pneumonitis cases. When you give immunotherapy, it happens sometimes that you have immune-related pneumonitis. But the risk was to imagine that those phenomena would increase or give rise to an excess of lung toxicity, and it’s not the case. It’s not the case in most of the trials where we try to combine radiation on the lung and immunotherapy. Decidedly, the mechanisms behind them are not cumulative or not synergistic. It’s just a fact that sometimes, radiation gives rise to some pneumonitis.

Transcript Edited for Clarity 
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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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