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Immunotherapy in Locally Advanced NSCLC

Panelists: Leora Horn, MD, MSc, FRCPC, Vanderbilt University Medical Center; Edward B. Garon, MD, David Geffen School of Medicine at UCLA; Thomas E. Stinchcombe, MD, Duke Cancer Institute
Published: Tuesday, Oct 16, 2018



Transcript: 

Leora Horn, MD, MSc, FRCPC: Moving into earlier stage disease, every drug in oncology is first tested in the metastatic and late stage settings. Then we start seeing it creep into earlier stage disease to see if we can cure more patients. In the patients who are getting concurrent chemoradiation, we’ve got 2 studies out there that have been presented at the ASCO [American Society of Clinical Oncology] Annual Meeting and the World Lung Conference. One was a large phase III trial—the PACIFIC trial—that compared 1 year of durvalumab to placebo in patients following concurrent chemoradiation therapy. Patients were randomized immediately after chemoradiation. And then we have the LUN 14-179 study from the Hoosier Cancer Research Network that looked at consolidation pembrolizumab in a similar patient population. So, we have a drug that’s FDA approved but pembrolizumab is out there. How are you using these drugs? Which drug are you using? What are you doing for patients with early-stage disease?

Thomas E. Stinchcombe, MD: For patients with stage III disease, I try to do the chemoradiation and then use durvalumab because that’s been proven to have a progression-free survival and overall survival benefit in times of metastasis. The toxicity is established as well. I’ve not interchanged PD-1 [programmed cell death 1], PD-L1 [programmed cell death ligand 1] inhibitors in the stage III setting. I’m not prepared to do so.

Edward B. Garon, MD: I agree. We do have robust data with durvalumab in that setting. Although the Hoosier Cancer Research Network study is obviously an impressive study, we don’t have the same regulatory approval and all of the things that go along with that. I’ve certainly used durvalumab in that setting.

Leora Horn, MD, MSc, FRCPC: We’ve heard the rumor that it is going to start coming out monthly. Hopefully when we have that data that’ll also make it a bit easier to give to those patients. How quickly are you starting durvalumab? The subset analysis suggested that if you start at less than 2 weeks there’s a better survival than if you start later. Are you starting patients at 2 weeks? Are patients ready to start after 6 weeks of concurrent radiation therapy?

Edward B. Garon, MD: I think there may be a discrepancy between the clinical trial population and the traditional population. I think that for fit, healthy patients that are otherwise in shape I would do it in that period of time. On the other hand, I am less convinced that it’s absolutely necessary. On a practical level, there’s a large part of our patient population for whom it’s just not really feasible.

Leora Horn, MD, MSc, FRCPC: What happens if they’re out at 7, 8 weeks? We had that study open. I don’t know if you had the trial open at your institutions?

Thomas E. Stinchcombe, MD: We did.

Edward B. Garon, MD: We did.

Leora Horn, MD, MSc, FRCPC: But it was a 6-week hard stop from when concurrent chemoradiation finished. So what happens if someone needs a little bit of extra time? Say they’re at 7, 8 weeks. What are you doing?

Thomas E. Stinchcombe, MD: I don’t feel strongly about the 14 days, but I feel that the 42 days, or 6 weeks—I’m pretty firm with that. I’m not saying that 7 weeks would be bad. You’re really trying to make sure that patients tolerate chemoradiation therapy without serious toxicity. Most of the people who are delayed either have radiation pneumonitis or bad esophagitis. I’m somewhat hesitant to add a therapy on when they haven’t recovered from the previous therapy. That is one of my concerns.

Transcript Edited for Clarity 
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Transcript: 

Leora Horn, MD, MSc, FRCPC: Moving into earlier stage disease, every drug in oncology is first tested in the metastatic and late stage settings. Then we start seeing it creep into earlier stage disease to see if we can cure more patients. In the patients who are getting concurrent chemoradiation, we’ve got 2 studies out there that have been presented at the ASCO [American Society of Clinical Oncology] Annual Meeting and the World Lung Conference. One was a large phase III trial—the PACIFIC trial—that compared 1 year of durvalumab to placebo in patients following concurrent chemoradiation therapy. Patients were randomized immediately after chemoradiation. And then we have the LUN 14-179 study from the Hoosier Cancer Research Network that looked at consolidation pembrolizumab in a similar patient population. So, we have a drug that’s FDA approved but pembrolizumab is out there. How are you using these drugs? Which drug are you using? What are you doing for patients with early-stage disease?

Thomas E. Stinchcombe, MD: For patients with stage III disease, I try to do the chemoradiation and then use durvalumab because that’s been proven to have a progression-free survival and overall survival benefit in times of metastasis. The toxicity is established as well. I’ve not interchanged PD-1 [programmed cell death 1], PD-L1 [programmed cell death ligand 1] inhibitors in the stage III setting. I’m not prepared to do so.

Edward B. Garon, MD: I agree. We do have robust data with durvalumab in that setting. Although the Hoosier Cancer Research Network study is obviously an impressive study, we don’t have the same regulatory approval and all of the things that go along with that. I’ve certainly used durvalumab in that setting.

Leora Horn, MD, MSc, FRCPC: We’ve heard the rumor that it is going to start coming out monthly. Hopefully when we have that data that’ll also make it a bit easier to give to those patients. How quickly are you starting durvalumab? The subset analysis suggested that if you start at less than 2 weeks there’s a better survival than if you start later. Are you starting patients at 2 weeks? Are patients ready to start after 6 weeks of concurrent radiation therapy?

Edward B. Garon, MD: I think there may be a discrepancy between the clinical trial population and the traditional population. I think that for fit, healthy patients that are otherwise in shape I would do it in that period of time. On the other hand, I am less convinced that it’s absolutely necessary. On a practical level, there’s a large part of our patient population for whom it’s just not really feasible.

Leora Horn, MD, MSc, FRCPC: What happens if they’re out at 7, 8 weeks? We had that study open. I don’t know if you had the trial open at your institutions?

Thomas E. Stinchcombe, MD: We did.

Edward B. Garon, MD: We did.

Leora Horn, MD, MSc, FRCPC: But it was a 6-week hard stop from when concurrent chemoradiation finished. So what happens if someone needs a little bit of extra time? Say they’re at 7, 8 weeks. What are you doing?

Thomas E. Stinchcombe, MD: I don’t feel strongly about the 14 days, but I feel that the 42 days, or 6 weeks—I’m pretty firm with that. I’m not saying that 7 weeks would be bad. You’re really trying to make sure that patients tolerate chemoradiation therapy without serious toxicity. Most of the people who are delayed either have radiation pneumonitis or bad esophagitis. I’m somewhat hesitant to add a therapy on when they haven’t recovered from the previous therapy. That is one of my concerns.

Transcript Edited for Clarity 
View Conference Coverage
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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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