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Chemotherapy Choices in the PACIFIC Trial

Panelists:Walter Curran, JR., MD, FACR, Winship Cancer Institute of Emory University; Mark G. Kris, MD, Memorial Sloan Kettering Cancer Center; Jyoti D. Patel, MD, University of Chicago
Published: Tuesday, Apr 03, 2018



Transcript: 

Mark Kris, MD: Jyoti, were there any issues, in this trial, with the chemotherapy piece?

Jyoti D. Patel, MD: Certainly, I think the design of the trial—at first, when we all heard about this— seemed a little bit reckless. “What, no rules?” “You can do whatever chemotherapy you want. You just can’t give consolidation.” So, again, for American practitioners who are so used to doing carboplatin and paclitaxel with consolidation cycles, this is a game changer. I think this reflects real-world practice, right? So many patients are getting induction. Up to one-quarter of patients did because of the availability of radiation therapists in different parts of the world. So, it may be that systemic therapy is started earlier? But all treatment needed to be completed prior to randomization, with no consolidation and a wide range of regimens. Clearly, the regimen didn’t really seem to matter either. When you look at the subgroup analysis, the arms were well balanced. It’s almost dealer’s choice. It’s very much a real-world scenario, again. This is one that was surprisingly alright. And so, it will be interesting to see how this sort of pans out in overall survival—with markers, never-smokers, and the whole mishmash.

Mark Kris, MD: Again, it was a randomized trial. Cross-trial comparisons are always tough. But we did have a comparison group here.

Walter J. Curran Jr., MD: Some people have commented that they believe the control arm had a surprisingly low progression-free survival. But keep in mind, there’s a lead time difference between this and the typical cooperative group trials. You’re counting the time from let’s say 2 to 10 weeks after chemoradiation, as opposed to prior to radiation. My recollection is that the median progression-free survival is just under 6 months. So, if you are comparing that with a RTOG trial, that would be more in the 8- to 9-month range.

Jyoti D. Patel, MD: Almost even up to 12, for some, because you could go up to 6 weeks after concurrent radiation.

Walter J. Curran Jr., MD: That’s correct, yes.

Mark Kris, MD: One other chemotherapy issue, in this trial, is the use of chemotherapy after immediate concurrent chemotherapy/radiation. What is your normal practice, now, once you’ve completed concurrent chemotherapy/radiation? Do you give additional chemotherapy?

Jyoti D. Patel, MD: Since this trial, for patients who have landed in my clinic, it has changed. I have now decided to either treat with cisplatin/pemetrexed or cisplatin/etoposide. I have really abandoned a weekly lower-dose approach with consolidation.

Mark Kris, MD: Are you still giving the consolidation chemotherapy?

Jyoti D. Patel, MD: No.

Mark Kris, MD: You have replaced it? One of the largest impacts of this trial is that the use of chemotherapy after simultaneous chemotherapy and radiation is going to go away. And for the record, there are clinical trials that show that additional chemotherapy—either continuing with what you did before, or switching to another non–cross-resistant option—did not improve outcomes. It only enhanced toxicity. So, this might be an additional benefit—limiting chemotherapy that is of marginal benefit. Some trials would say that there is no benefit; but, actually, some harm.

Transcript Edited for Clarity 
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Transcript: 

Mark Kris, MD: Jyoti, were there any issues, in this trial, with the chemotherapy piece?

Jyoti D. Patel, MD: Certainly, I think the design of the trial—at first, when we all heard about this— seemed a little bit reckless. “What, no rules?” “You can do whatever chemotherapy you want. You just can’t give consolidation.” So, again, for American practitioners who are so used to doing carboplatin and paclitaxel with consolidation cycles, this is a game changer. I think this reflects real-world practice, right? So many patients are getting induction. Up to one-quarter of patients did because of the availability of radiation therapists in different parts of the world. So, it may be that systemic therapy is started earlier? But all treatment needed to be completed prior to randomization, with no consolidation and a wide range of regimens. Clearly, the regimen didn’t really seem to matter either. When you look at the subgroup analysis, the arms were well balanced. It’s almost dealer’s choice. It’s very much a real-world scenario, again. This is one that was surprisingly alright. And so, it will be interesting to see how this sort of pans out in overall survival—with markers, never-smokers, and the whole mishmash.

Mark Kris, MD: Again, it was a randomized trial. Cross-trial comparisons are always tough. But we did have a comparison group here.

Walter J. Curran Jr., MD: Some people have commented that they believe the control arm had a surprisingly low progression-free survival. But keep in mind, there’s a lead time difference between this and the typical cooperative group trials. You’re counting the time from let’s say 2 to 10 weeks after chemoradiation, as opposed to prior to radiation. My recollection is that the median progression-free survival is just under 6 months. So, if you are comparing that with a RTOG trial, that would be more in the 8- to 9-month range.

Jyoti D. Patel, MD: Almost even up to 12, for some, because you could go up to 6 weeks after concurrent radiation.

Walter J. Curran Jr., MD: That’s correct, yes.

Mark Kris, MD: One other chemotherapy issue, in this trial, is the use of chemotherapy after immediate concurrent chemotherapy/radiation. What is your normal practice, now, once you’ve completed concurrent chemotherapy/radiation? Do you give additional chemotherapy?

Jyoti D. Patel, MD: Since this trial, for patients who have landed in my clinic, it has changed. I have now decided to either treat with cisplatin/pemetrexed or cisplatin/etoposide. I have really abandoned a weekly lower-dose approach with consolidation.

Mark Kris, MD: Are you still giving the consolidation chemotherapy?

Jyoti D. Patel, MD: No.

Mark Kris, MD: You have replaced it? One of the largest impacts of this trial is that the use of chemotherapy after simultaneous chemotherapy and radiation is going to go away. And for the record, there are clinical trials that show that additional chemotherapy—either continuing with what you did before, or switching to another non–cross-resistant option—did not improve outcomes. It only enhanced toxicity. So, this might be an additional benefit—limiting chemotherapy that is of marginal benefit. Some trials would say that there is no benefit; but, actually, some harm.

Transcript Edited for Clarity 
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