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Concurrent Chemoradiotherapy in Stage III NSCLC

Panelists: Mark A. Socinski, MD, Florida Hospital Cancer Institute; Karen Kelly, MD, UC Davis Comprehensive Cancer Center; Corey J. Langer, MD, FACP, University of Pennsylvania; Benjamin P. Levy, MD, Sibley Memorial Hospital
Published: Friday, Jul 27, 2018



Transcript: 

Mark A. Socinski, MD: Now let’s transition to stage 3 disease. Many of us on this panel have extensive experience in stage 3 disease. Before we start talking about what I think is probably one of the more exciting phase III results in the past several years, based on the PACIFIC trial, I wanted Dr. Langer to kind of level set us, pre-PACIFIC, on your standard of care. What did you do in your practice? What do you think is acceptable in practice?

Corey J. Langer, MD, FACP: I think we’ve all come to accept that certainly in good performance status patients, concurrent chemoradiation is the standard of care. Over the past 25 years, there have been at least 10 separate prospective clinical trials that have shown that chemotherapy, when added to radiation—whether it’s induction, concurrent—is better than radiation alone. Of 4 trials that directly compared sequential, or asynchronous chemoradiation, to concurrent, 3 of the 4 showed a clear benefit for concurrent. That, of course, is confirmed in the meta-analysis.

But in the last 10 to 15 years, we’ve sort of stagnated. There were attempts to look at higher doses of radiation. They were marginally higher—20% to 25%. In RTOG 0617, appallingly negative. The higher-dose arm actually had an inferior outcome compared with the low-dose arm. There were attempts to graft monoclonal antibodies targeting EGFR. Cetuximab—at least no detriment but certainly no advantage. We did not move the needle 1 bit. There were attempts that looked at consolidation, non–cross-resistant chemotherapy, or the same chemotherapy after the completion of chemoradiation. And at least in those trials that formerly compared that approach—docetaxel versus observation—again, completely negative. In truth, with the regimen that I have typically used, weekly paclitaxel plus carboplatin with radiotherapy followed by 2 cycles of paclitaxel plus carboplatin, we never proved that those 2 cycles were actually better than observation.

Mark A. Socinski, MD: Either before or after.

Corey J. Langer, MD, FACP: Certainly before—we proved that they weren’t. But after—we never even addressed that question.

Mark A. Socinski, MD: I don’t even want to get into that debate. And don’t forget about that important gefitinib consolidation.

Karen Kelly, MD: I was waiting for you to say that.

Corey J. Langer, MD, FACP: That is another example of a trial that not only failed to show an advantage but also, surprisingly, showed a detriment that none of us anticipated. I was on the Data Safety Monitoring Committee for that trial. First, they were on label, and I thought, “Holy cow, gefitinib is showing advantage.” And then the head of the statistics department at SWOG actually labeled those curves. Lo and behold, I was shocked. Folks like me had a lot of skepticism about any new approaches here.

Transcript Edited for Clarity

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Transcript: 

Mark A. Socinski, MD: Now let’s transition to stage 3 disease. Many of us on this panel have extensive experience in stage 3 disease. Before we start talking about what I think is probably one of the more exciting phase III results in the past several years, based on the PACIFIC trial, I wanted Dr. Langer to kind of level set us, pre-PACIFIC, on your standard of care. What did you do in your practice? What do you think is acceptable in practice?

Corey J. Langer, MD, FACP: I think we’ve all come to accept that certainly in good performance status patients, concurrent chemoradiation is the standard of care. Over the past 25 years, there have been at least 10 separate prospective clinical trials that have shown that chemotherapy, when added to radiation—whether it’s induction, concurrent—is better than radiation alone. Of 4 trials that directly compared sequential, or asynchronous chemoradiation, to concurrent, 3 of the 4 showed a clear benefit for concurrent. That, of course, is confirmed in the meta-analysis.

But in the last 10 to 15 years, we’ve sort of stagnated. There were attempts to look at higher doses of radiation. They were marginally higher—20% to 25%. In RTOG 0617, appallingly negative. The higher-dose arm actually had an inferior outcome compared with the low-dose arm. There were attempts to graft monoclonal antibodies targeting EGFR. Cetuximab—at least no detriment but certainly no advantage. We did not move the needle 1 bit. There were attempts that looked at consolidation, non–cross-resistant chemotherapy, or the same chemotherapy after the completion of chemoradiation. And at least in those trials that formerly compared that approach—docetaxel versus observation—again, completely negative. In truth, with the regimen that I have typically used, weekly paclitaxel plus carboplatin with radiotherapy followed by 2 cycles of paclitaxel plus carboplatin, we never proved that those 2 cycles were actually better than observation.

Mark A. Socinski, MD: Either before or after.

Corey J. Langer, MD, FACP: Certainly before—we proved that they weren’t. But after—we never even addressed that question.

Mark A. Socinski, MD: I don’t even want to get into that debate. And don’t forget about that important gefitinib consolidation.

Karen Kelly, MD: I was waiting for you to say that.

Corey J. Langer, MD, FACP: That is another example of a trial that not only failed to show an advantage but also, surprisingly, showed a detriment that none of us anticipated. I was on the Data Safety Monitoring Committee for that trial. First, they were on label, and I thought, “Holy cow, gefitinib is showing advantage.” And then the head of the statistics department at SWOG actually labeled those curves. Lo and behold, I was shocked. Folks like me had a lot of skepticism about any new approaches here.

Transcript Edited for Clarity
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