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NSCLC: Treating Progression After Chemo and I-O

Panelists: Charu Aggarwal, MD, MPH, Hospital of the University of Pennsylvania; Hossein Borghaei, DO, Fox Chase Cancer Center; H. Jack West, MD, Swedish Cancer Institute
Published: Monday, Feb 04, 2019



Transcript: 

H. Jack West, MD: As we move to a standard for the majority of patients that includes chemotherapy combined with pembrolizumab [pembro], or perhaps other chemotherapy and I-O [immuno-oncology] combinations in the future, that merges 2 lines of therapy previously. We typically did immunotherapy followed by chemotherapy, or for more patients, chemotherapy followed by immunotherapy. And that leads many of us, patients and oncologists, to ask: What can we do after that? So what would you say we should do after a patient has progressed on chemotherapy/pembro or even a sequential approach? What are we left with?

Hossein Borghaei, DO: If you start with pembro alone, for the greater than 50%, then you have a clear option of doing a platinum doublet, and I think that’s a really good option. So if you start with I-O, you can always go to a platinum doublet. If you start with chemotherapy alone, you can always go to an I-O. We have data in favor of that. You’re in trouble if you start with chemotherapy and I-O, because what you’ve got left after that is what we try to run away from, which is your docetaxel, and your gemcitabine, and the weekly Taxol, and things like that, clearly in the absence of a clinical trial. I think in our institutions we try to put people on trials to investigate this I-O and chemo-refractory patient population and come up with something that can be a little bit more meaningful. But for everyday practice, you go back to docetaxel, you go back to docetaxel and ramucirumab, you go again to the stuff that, as I said, immunotherapy surpassed and was shown to be good.

But I don’t see a clear winner in all this. There have been a couple of really interesting phase I and II studies, some of them even with randomized trials. Again, there was a very nice abstract presented in Toronto combining an epigenetic and an I-O in an I-O refractory patient population. The results were interesting. We might even have a biomarker, in terms of monocytes, for that particular regimen, but it’s not a phase III study. It’s not a home run. There’s this combination of ramucirumab plus a VEGF inhibitor and pembro plus ramucirumab that is very interesting and has been presented at a couple of different meetings. It is going on to a bigger study to see if it has the clinical efficacy that you need. So we don’t have clear winners coming up anytime soon, but there are a lot of studies, again in terms of phase Is and phase IIs, looking at various combinations to see what would be beneficial.

H. Jack West, MD: Charu, what’s your approach, particularly focusing on the chemo/I-O recipients who progress?

Charu Aggarwal, MD, MPH: I cringe and offer docetaxel and ramucirumab.

H. Jack West, MD: Do you think there’s anything to the retrospective data? There are some suggestions that following immunotherapy, response rates can be higher to conventional chemotherapy. I’ve been encouraged, and I have to say, I’ve used more ramucirumab with docetaxel, sometimes lowering that docetaxel to 60 [mg/m2]. But I’m using that more and more as patients are progressing but still have a good performance status and are candidates for more. And I’ve seen better results than I would have expected to see, certainly from docetaxel monotherapy and maybe even docetaxel and ramucirumab before the era of them getting immunotherapy. So I think we need to learn more about this, but it may not be as dire.

Charu Aggarwal, MD, MPH: I agree, and I’ve actually had spectacular responses to single-agent chemotherapy, in which I’ve had the hospice conversation and the patients have said, “No, I still want to do something.” I’ve given them chemotherapy as a single agent, really hoping for nothing and they’re here a year later doing well after having had the hospice conversation a year ago. So definitely, I think it’s humbling.

H. Jack West, MD: But this is also an area that’s fertile for further study. I think 1 thing that maybe we should close on is we have not seen data to support very positive results for just trying NIVO/IPI [nivolumab plus ipilimumab] after someone has been on pembro, or switching from 1 checkpoint inhibitor to another. I haven’t even heard of an anecdotal case that has gone well, let alone data. So that’s really not a supported approach.

Transcript Edited for Clarity

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Transcript: 

H. Jack West, MD: As we move to a standard for the majority of patients that includes chemotherapy combined with pembrolizumab [pembro], or perhaps other chemotherapy and I-O [immuno-oncology] combinations in the future, that merges 2 lines of therapy previously. We typically did immunotherapy followed by chemotherapy, or for more patients, chemotherapy followed by immunotherapy. And that leads many of us, patients and oncologists, to ask: What can we do after that? So what would you say we should do after a patient has progressed on chemotherapy/pembro or even a sequential approach? What are we left with?

Hossein Borghaei, DO: If you start with pembro alone, for the greater than 50%, then you have a clear option of doing a platinum doublet, and I think that’s a really good option. So if you start with I-O, you can always go to a platinum doublet. If you start with chemotherapy alone, you can always go to an I-O. We have data in favor of that. You’re in trouble if you start with chemotherapy and I-O, because what you’ve got left after that is what we try to run away from, which is your docetaxel, and your gemcitabine, and the weekly Taxol, and things like that, clearly in the absence of a clinical trial. I think in our institutions we try to put people on trials to investigate this I-O and chemo-refractory patient population and come up with something that can be a little bit more meaningful. But for everyday practice, you go back to docetaxel, you go back to docetaxel and ramucirumab, you go again to the stuff that, as I said, immunotherapy surpassed and was shown to be good.

But I don’t see a clear winner in all this. There have been a couple of really interesting phase I and II studies, some of them even with randomized trials. Again, there was a very nice abstract presented in Toronto combining an epigenetic and an I-O in an I-O refractory patient population. The results were interesting. We might even have a biomarker, in terms of monocytes, for that particular regimen, but it’s not a phase III study. It’s not a home run. There’s this combination of ramucirumab plus a VEGF inhibitor and pembro plus ramucirumab that is very interesting and has been presented at a couple of different meetings. It is going on to a bigger study to see if it has the clinical efficacy that you need. So we don’t have clear winners coming up anytime soon, but there are a lot of studies, again in terms of phase Is and phase IIs, looking at various combinations to see what would be beneficial.

H. Jack West, MD: Charu, what’s your approach, particularly focusing on the chemo/I-O recipients who progress?

Charu Aggarwal, MD, MPH: I cringe and offer docetaxel and ramucirumab.

H. Jack West, MD: Do you think there’s anything to the retrospective data? There are some suggestions that following immunotherapy, response rates can be higher to conventional chemotherapy. I’ve been encouraged, and I have to say, I’ve used more ramucirumab with docetaxel, sometimes lowering that docetaxel to 60 [mg/m2]. But I’m using that more and more as patients are progressing but still have a good performance status and are candidates for more. And I’ve seen better results than I would have expected to see, certainly from docetaxel monotherapy and maybe even docetaxel and ramucirumab before the era of them getting immunotherapy. So I think we need to learn more about this, but it may not be as dire.

Charu Aggarwal, MD, MPH: I agree, and I’ve actually had spectacular responses to single-agent chemotherapy, in which I’ve had the hospice conversation and the patients have said, “No, I still want to do something.” I’ve given them chemotherapy as a single agent, really hoping for nothing and they’re here a year later doing well after having had the hospice conversation a year ago. So definitely, I think it’s humbling.

H. Jack West, MD: But this is also an area that’s fertile for further study. I think 1 thing that maybe we should close on is we have not seen data to support very positive results for just trying NIVO/IPI [nivolumab plus ipilimumab] after someone has been on pembro, or switching from 1 checkpoint inhibitor to another. I haven’t even heard of an anecdotal case that has gone well, let alone data. So that’s really not a supported approach.

Transcript Edited for Clarity
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