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Optimal Sequencing in Squamous Non-Small Cell Lung Cancer

Panelists:Edward S. Kim, MD, FACP, Carolinas HealthCare System; Benjamin Levy, MD, Mount Sinai Hospital; Paul K. Paik, MD, Memorial Sloan Kettering Cancer Center
Published: Wednesday, Jun 08, 2016


Transcript:

Benjamin Levy, MD:
We’ve got a lot of options that we’ve talked about today—the docetaxel, the docetaxel/ramucirumab, the afatinib, chemotherapy options. What is the right sequence? Is there a right sequence, as we finish up here? What is the first, second, third, fourth? And we’re excluding clinical trials here. All of us participate rigorously in clinical trials. But is there a right sequence here or is it just individualized, as Ed you’d said before?

Edward S. Kim, MD, FACP: Today or a year from now?

Benjamin Levy, MD: Let’s go today.

Edward S. Kim, MD, FACP: Okay. I had a case years ago where I had a young lady who had squamous, very odd, and they thought it was small-cell. They gave her one cycle of carboplatin/etoposide and it didn’t work, and then they said, no, [that it was] squamous, and for some reason they gave her carboplatin/Taxol/Avastin for one cycle. She survived that, and then she came to see me and she was in bad shape. She was on oxygen, 39-year-old single mother, had a young child. And I said, “This is a time where we’ve just got to go for the gold. This is no way a pattern of what you should mirror from this.” So I, at the time, said let’s try, if we can get them, carboplatin/nab-paclitaxel and cetuximab. And those are the guns, right?

So today, I would imagine, I would love to use a carboplatin/nab-paclitaxel/necitumumab frontline; I know that study is being done. But if you want to try and stack some efficacy, see what necitumumab did with this gemcitabine/cisplatin on top of what Abraxane does on its own, that’s really quite interesting as long as it’s safe to give. But right now, we go with Abraxane-based regimens up front. That’s our default. So it’s, in light of down the road, integrating a checkpoint inhibitor; it’s carboplatin/nab-paclitaxel. Then second-line, it’s nivolumab and then consideration of a docetaxel/ramucirumab strategy versus something less intensive.

Benjamin Levy, MD: I think that would be where we are in line, too. All of our patients have been offered the ABOUND study with carboplatin/Abraxane, with maintenance we have a checkpoint inhibitor study as well. But outside of that, the carboplatin/Abraxane, immunotherapy followed by docetaxel/ramucirumab. I would argue that a lot of our patients who get to third-line may not be eligible for docetaxel/ramucirumab. Those patients, maybe I would consider a TKI, depending on how they look. Maybe I would consider another cytotoxic single-agent drug and then transition from there. Paul, your final thoughts on sequencing overall.

Paul K. Paik, MD: The sequence is similar. I tend to be a little bit more agnostic in terms of the first-line chemotherapy regimen, in part because looking at the overall landscape for the research portfolio, these things sometimes need to be taken into consideration. But I think it’s perfectly reasonable. The preferred regimens are carboplatin/Abraxane if you go down a taxane route. Carboplatin/gemcitabine is perfectly reasonable. A lot of the patients we end up seeing are second opinions, third opinions for what’s been going on. And we have to be careful in terms of what the data show for what any individual oncologist has recommended.

When you look at the data for first-line regimens, there’s not a lot that you can stand on in terms of the differences. Immune checkpoint inhibition, absent in autoimmune disease, or being never-smokers, [which is] unusual for squamous lung cancer, certainly is in the second-line setting. Then chemotherapy/ramucirumab. Docetaxel/ramucirumab can be a little bit limiting. I would love to see, at some point, data for gemcitabine/ramucirumab, something like that. Whether we’ll ever see that, whoever knows, but it would sort of free up options also because single-agent gemcitabine is not great.

I agree, though. By the third-line setting, sometimes docetaxel/ramucirumab is hard to give, certainly Q3 week and even divided weekly is better tolerated. I find dose reductions with the docetaxel are required a lot by that point. But I’ve seen responses, and it certainly is reasonable to give with an expectation of some degree of response. And then after that, you’re far afield and that’s where we just got to get better in terms of the work we’re doing, all of us.

Benjamin Levy, MD: So this has been a terrific discussion. We’ve discussed a lot of information about the latest in the treatment of squamous non-small cell lung cancer. Before we end this discussion, I’d like to just get some final thoughts from each of our panelists. Dr. Kim, final thoughts on today’s discussions and where we’re heading.

Edward S. Kim, MD, FACP: I’ve enjoyed the discussion. I always like talking about practical clinical aspects engrossed with the science. The bottom line is that there are many more options for patients who have squamous histology lung cancer. We’re definitely moving in the right direction. We have more options for treatment, but we still have to sort out stratification with biomarkers and enrichment. The science of the trials are built to answer some of those questions. As I had mentioned before, we need some serendipity as well. We need to accidentally find someone who responds really well and figure out why they did, and see if we can find that marker. I’m pleased with the direction it’s going.

Benjamin Levy, MD: Paul?

Paul K. Paik, MD: I think I mirror that. I mean, the fact that we’ve gotten so many new agents approved in effectively a year’s time, that’s unprecedented really. And yet if we look at lung adenocarcinoma as the cousin or the sister or brother, they’re far better off. They’re far better off, by-and-large, because targeted therapy is reality for them. Despite the excitement with immune checkpoint inhibition, this is an untapped arena and something to keep our eyes on, and something that should remain a focus—not just in combination, as the tendency is, to do willy-nilly combinations with targeted therapy that may or may not make sense—but actually really honing in on combinations that make sense, in order to really see these gains that we’ve seen with other TKIs in lung adenocarcinomas.

Benjamin Levy, MD: I would agree with you both that the amount of options we have supported by science is tremendously exciting for patients with advanced-stage non-small cell lung cancer, specifically squamous cell. I’m going to take the approach that I always do in my final thoughts and remind people that these treatments, unfortunately, despite the excitement, are palliative in nature, not curative. And we really have to be on the forefront and leading the discussion about preventative measures for lung cancer; smoking cessation for patients who are smoking who have not developed lung cancer, and also CT screening, picking up these cancers early. Clearly a little bit different approach than what we’ve been talking about today, but we do need plasma-enrichment strategies for patients who have nodules on scans.

So, yes, tremendous excitement with all the drugs. I’m one of the people who has welcomed these with open arms. But medical oncologists also have to lead a discussion with their primary care physicians about how to prevent this disease from happening from the first place. On behalf of our panel, we want to thank you for joining us.

Transcript Edited for Clarity
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Transcript:

Benjamin Levy, MD:
We’ve got a lot of options that we’ve talked about today—the docetaxel, the docetaxel/ramucirumab, the afatinib, chemotherapy options. What is the right sequence? Is there a right sequence, as we finish up here? What is the first, second, third, fourth? And we’re excluding clinical trials here. All of us participate rigorously in clinical trials. But is there a right sequence here or is it just individualized, as Ed you’d said before?

Edward S. Kim, MD, FACP: Today or a year from now?

Benjamin Levy, MD: Let’s go today.

Edward S. Kim, MD, FACP: Okay. I had a case years ago where I had a young lady who had squamous, very odd, and they thought it was small-cell. They gave her one cycle of carboplatin/etoposide and it didn’t work, and then they said, no, [that it was] squamous, and for some reason they gave her carboplatin/Taxol/Avastin for one cycle. She survived that, and then she came to see me and she was in bad shape. She was on oxygen, 39-year-old single mother, had a young child. And I said, “This is a time where we’ve just got to go for the gold. This is no way a pattern of what you should mirror from this.” So I, at the time, said let’s try, if we can get them, carboplatin/nab-paclitaxel and cetuximab. And those are the guns, right?

So today, I would imagine, I would love to use a carboplatin/nab-paclitaxel/necitumumab frontline; I know that study is being done. But if you want to try and stack some efficacy, see what necitumumab did with this gemcitabine/cisplatin on top of what Abraxane does on its own, that’s really quite interesting as long as it’s safe to give. But right now, we go with Abraxane-based regimens up front. That’s our default. So it’s, in light of down the road, integrating a checkpoint inhibitor; it’s carboplatin/nab-paclitaxel. Then second-line, it’s nivolumab and then consideration of a docetaxel/ramucirumab strategy versus something less intensive.

Benjamin Levy, MD: I think that would be where we are in line, too. All of our patients have been offered the ABOUND study with carboplatin/Abraxane, with maintenance we have a checkpoint inhibitor study as well. But outside of that, the carboplatin/Abraxane, immunotherapy followed by docetaxel/ramucirumab. I would argue that a lot of our patients who get to third-line may not be eligible for docetaxel/ramucirumab. Those patients, maybe I would consider a TKI, depending on how they look. Maybe I would consider another cytotoxic single-agent drug and then transition from there. Paul, your final thoughts on sequencing overall.

Paul K. Paik, MD: The sequence is similar. I tend to be a little bit more agnostic in terms of the first-line chemotherapy regimen, in part because looking at the overall landscape for the research portfolio, these things sometimes need to be taken into consideration. But I think it’s perfectly reasonable. The preferred regimens are carboplatin/Abraxane if you go down a taxane route. Carboplatin/gemcitabine is perfectly reasonable. A lot of the patients we end up seeing are second opinions, third opinions for what’s been going on. And we have to be careful in terms of what the data show for what any individual oncologist has recommended.

When you look at the data for first-line regimens, there’s not a lot that you can stand on in terms of the differences. Immune checkpoint inhibition, absent in autoimmune disease, or being never-smokers, [which is] unusual for squamous lung cancer, certainly is in the second-line setting. Then chemotherapy/ramucirumab. Docetaxel/ramucirumab can be a little bit limiting. I would love to see, at some point, data for gemcitabine/ramucirumab, something like that. Whether we’ll ever see that, whoever knows, but it would sort of free up options also because single-agent gemcitabine is not great.

I agree, though. By the third-line setting, sometimes docetaxel/ramucirumab is hard to give, certainly Q3 week and even divided weekly is better tolerated. I find dose reductions with the docetaxel are required a lot by that point. But I’ve seen responses, and it certainly is reasonable to give with an expectation of some degree of response. And then after that, you’re far afield and that’s where we just got to get better in terms of the work we’re doing, all of us.

Benjamin Levy, MD: So this has been a terrific discussion. We’ve discussed a lot of information about the latest in the treatment of squamous non-small cell lung cancer. Before we end this discussion, I’d like to just get some final thoughts from each of our panelists. Dr. Kim, final thoughts on today’s discussions and where we’re heading.

Edward S. Kim, MD, FACP: I’ve enjoyed the discussion. I always like talking about practical clinical aspects engrossed with the science. The bottom line is that there are many more options for patients who have squamous histology lung cancer. We’re definitely moving in the right direction. We have more options for treatment, but we still have to sort out stratification with biomarkers and enrichment. The science of the trials are built to answer some of those questions. As I had mentioned before, we need some serendipity as well. We need to accidentally find someone who responds really well and figure out why they did, and see if we can find that marker. I’m pleased with the direction it’s going.

Benjamin Levy, MD: Paul?

Paul K. Paik, MD: I think I mirror that. I mean, the fact that we’ve gotten so many new agents approved in effectively a year’s time, that’s unprecedented really. And yet if we look at lung adenocarcinoma as the cousin or the sister or brother, they’re far better off. They’re far better off, by-and-large, because targeted therapy is reality for them. Despite the excitement with immune checkpoint inhibition, this is an untapped arena and something to keep our eyes on, and something that should remain a focus—not just in combination, as the tendency is, to do willy-nilly combinations with targeted therapy that may or may not make sense—but actually really honing in on combinations that make sense, in order to really see these gains that we’ve seen with other TKIs in lung adenocarcinomas.

Benjamin Levy, MD: I would agree with you both that the amount of options we have supported by science is tremendously exciting for patients with advanced-stage non-small cell lung cancer, specifically squamous cell. I’m going to take the approach that I always do in my final thoughts and remind people that these treatments, unfortunately, despite the excitement, are palliative in nature, not curative. And we really have to be on the forefront and leading the discussion about preventative measures for lung cancer; smoking cessation for patients who are smoking who have not developed lung cancer, and also CT screening, picking up these cancers early. Clearly a little bit different approach than what we’ve been talking about today, but we do need plasma-enrichment strategies for patients who have nodules on scans.

So, yes, tremendous excitement with all the drugs. I’m one of the people who has welcomed these with open arms. But medical oncologists also have to lead a discussion with their primary care physicians about how to prevent this disease from happening from the first place. On behalf of our panel, we want to thank you for joining us.

Transcript Edited for Clarity
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