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Optimal Chemotherapy for Squamous NSCLC

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: Monday, Mar 21, 2016


Transcript:

Benjamin Levy, MD:
Let’s move on to perhaps a more common clinical scenario of giving chemotherapy to treatment-naïve patients with advanced squamous cell lung cancer and potentially talking about the optimal chemotherapy regimen. I look at chemotherapy regimens for squamous cell as a story of competing standards really. We have the cisplatin/gemcitabine regimen that emerged out of the Scagliotti data, a very large study randomizing patients to cisplatin/gemcitabine versus cisplatin/pemetrexed.

It included both adenocarcinoma and squamous cell patients, and we saw in a subset of patients with squamous cell—which I think are around 450 patients—a benefit with cisplatin/gemcitabine in survival over cisplatin/pemetrexed. And we saw, obviously, just the opposite for patients with non-squamous histology. There seemed to be a preferential activity with cisplatin/pemetrexed over cisplatin/gemcitabine in the non-squamous population. So we have cisplatin/gemcitabine from that data. We’ve got carboplatin/Taxol hanging on as still a competitive regimen, I think sometimes often in the community, but perhaps in academic centers as well.

The carboplatin/Taxol data emerging out of the ECOG 1594 study showing a relative equivalence to other platinum-based regimens with perhaps better tolerability, and, of course, that study included squamous patients as well. And more recently, we’ve had carboplatin/nab-paclitaxel come out and having some very competitive and compelling data. This was a large phase III trial of more than 1000 patients randomized 1:1 to carboplatin solvent–based paclitaxel versus carboplatin/nab-paclitaxel in the intention-to-treat population. And this study included both adenocarcinoma and squamous patients. In the intention-to-treat population there was a response rate advantage with carboplatin/nab-paclitaxel.

But, interestingly, in the subset of patients with squamous cell, we saw that this benefit was more pronounced in response rate. We saw a response rate in a subset of squamous cells of 41% versus 24% in the carboplatin/paclitaxel arm. There was a nonsignificant trend in overall survival in the squamous cell population with carboplatin/nab-paclitaxel versus carboplatin/Taxol.

Importantly, also, the adverse events seemed to be a little more favorable in the carboplatin/nab-paclitaxel arm. There was less neuropathy, obviously; less myalgias and arthralgias but more neutropenia; more anemia and thrombocytopenia. So these data have clearly come out and changed the way that we may treat patients with squamous cell cancers. Interestingly in that study also, the subset of patients over the age of 70, for reasons I’m still trying to grapple with, had a survival advantage.

We have to be careful with subset analyses, but there was a subset analysis done on the patients over the age of 70 that showed a survival advantage with carboplatin/nab-paclitaxel over carboplatin/paclitaxel. So we’ve got cisplatin/gemcitabine, we’ve got carboplatin/paclitaxel, and we’ve got carboplatin/nab-paclitaxel.

I’ll just open this up, and maybe we can start with Ed, your impressions of the data. Is there an optimal chemotherapy regimen based on what we have, and what are you using and why?

Edward S. Kim, MD, FACP: Everybody get in a comfortable position. I’m going to break it down right now. I always like to look at things we report on and then if you were to design a similar study, what would you do differently? It’s like looking at it forward and backwards. So the Scagliotti study of gemcitabine/cisplatin versus pemetrexed/cisplatin was a very logical study to design at the time. It was in both histologies, non-squamous and squamous.

Gemcitabine/cisplatin was going off patent in Europe and Eli Lilly needed another regimen to replace it, and we all know pemetrexed-based regimens are really phenomenal and one of the few cytotoxics that has really changed the treatment paradigm clinically for people in their maintenance setting, second-line setting, and first-line setting. But it also changed the paradigm in that it doesn’t work in squamous tumors. In fact, conglomerating the data, it’s actually harmful in squamous patients. So, for me to even state that gemcitabine/cisplatin came out any type of winner in that trial is not correct.

Benjamin Levy, MD: So you think cisplatin/pemetrexed is such an inferior regimen in that patient population that it’s hard for cisplatin/gemcitabine not to show a preferential activity versus cisplatin/pemetrexed?

Edward S. Kim, MD, FACP: It’s sort of like trying to boost my ego on how fast I may be and getting my 10 year-old out on the track and beating him. I’m like, ‘Yeah, I did it.’ I have maybe a year or two left of this. It doesn’t speak to that I’m fast; it speaks to him that he’s slow. And so the numbers for gemcitabine/cisplatin were very similar in the survival in both the squamous and the non-squamous patients, and they were both about 10 months. So, to me, to sort of de facto say that gemcitabine/cisplatin is all of a sudden a great regimen for squamous is a misnomer, and I don’t like when I hear that.

Talking about the Taxol aspect—carboplatin/paclitaxel—yes, it is amazing. That drug has stuck around for ages, hasn’t it? And your comment was, well, out in the community. Let’s not forget Dr. Schiller and a lot of these thought leaders designed this study, Dr. Belani Dr. Schiller. And so these are academic thought leaders who designed these studies, reported them at ASCO, and presented them in high-profile journals. So I would say the example was set from the top and has permeated to the bottom now.

Favorable reimbursement, favorable other things certainly have perpetuated that. I fight the same battle. I feel the exact same way. I don’t know why this drug continues to be used so often when we have these other alternatives, but it speaks to the fact that people still see very adequate tolerable side effects and activity.
                                                                                                                                                                                                                                                                                                                
Transcript Edited for Clarity
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Transcript:

Benjamin Levy, MD:
Let’s move on to perhaps a more common clinical scenario of giving chemotherapy to treatment-naïve patients with advanced squamous cell lung cancer and potentially talking about the optimal chemotherapy regimen. I look at chemotherapy regimens for squamous cell as a story of competing standards really. We have the cisplatin/gemcitabine regimen that emerged out of the Scagliotti data, a very large study randomizing patients to cisplatin/gemcitabine versus cisplatin/pemetrexed.

It included both adenocarcinoma and squamous cell patients, and we saw in a subset of patients with squamous cell—which I think are around 450 patients—a benefit with cisplatin/gemcitabine in survival over cisplatin/pemetrexed. And we saw, obviously, just the opposite for patients with non-squamous histology. There seemed to be a preferential activity with cisplatin/pemetrexed over cisplatin/gemcitabine in the non-squamous population. So we have cisplatin/gemcitabine from that data. We’ve got carboplatin/Taxol hanging on as still a competitive regimen, I think sometimes often in the community, but perhaps in academic centers as well.

The carboplatin/Taxol data emerging out of the ECOG 1594 study showing a relative equivalence to other platinum-based regimens with perhaps better tolerability, and, of course, that study included squamous patients as well. And more recently, we’ve had carboplatin/nab-paclitaxel come out and having some very competitive and compelling data. This was a large phase III trial of more than 1000 patients randomized 1:1 to carboplatin solvent–based paclitaxel versus carboplatin/nab-paclitaxel in the intention-to-treat population. And this study included both adenocarcinoma and squamous patients. In the intention-to-treat population there was a response rate advantage with carboplatin/nab-paclitaxel.

But, interestingly, in the subset of patients with squamous cell, we saw that this benefit was more pronounced in response rate. We saw a response rate in a subset of squamous cells of 41% versus 24% in the carboplatin/paclitaxel arm. There was a nonsignificant trend in overall survival in the squamous cell population with carboplatin/nab-paclitaxel versus carboplatin/Taxol.

Importantly, also, the adverse events seemed to be a little more favorable in the carboplatin/nab-paclitaxel arm. There was less neuropathy, obviously; less myalgias and arthralgias but more neutropenia; more anemia and thrombocytopenia. So these data have clearly come out and changed the way that we may treat patients with squamous cell cancers. Interestingly in that study also, the subset of patients over the age of 70, for reasons I’m still trying to grapple with, had a survival advantage.

We have to be careful with subset analyses, but there was a subset analysis done on the patients over the age of 70 that showed a survival advantage with carboplatin/nab-paclitaxel over carboplatin/paclitaxel. So we’ve got cisplatin/gemcitabine, we’ve got carboplatin/paclitaxel, and we’ve got carboplatin/nab-paclitaxel.

I’ll just open this up, and maybe we can start with Ed, your impressions of the data. Is there an optimal chemotherapy regimen based on what we have, and what are you using and why?

Edward S. Kim, MD, FACP: Everybody get in a comfortable position. I’m going to break it down right now. I always like to look at things we report on and then if you were to design a similar study, what would you do differently? It’s like looking at it forward and backwards. So the Scagliotti study of gemcitabine/cisplatin versus pemetrexed/cisplatin was a very logical study to design at the time. It was in both histologies, non-squamous and squamous.

Gemcitabine/cisplatin was going off patent in Europe and Eli Lilly needed another regimen to replace it, and we all know pemetrexed-based regimens are really phenomenal and one of the few cytotoxics that has really changed the treatment paradigm clinically for people in their maintenance setting, second-line setting, and first-line setting. But it also changed the paradigm in that it doesn’t work in squamous tumors. In fact, conglomerating the data, it’s actually harmful in squamous patients. So, for me to even state that gemcitabine/cisplatin came out any type of winner in that trial is not correct.

Benjamin Levy, MD: So you think cisplatin/pemetrexed is such an inferior regimen in that patient population that it’s hard for cisplatin/gemcitabine not to show a preferential activity versus cisplatin/pemetrexed?

Edward S. Kim, MD, FACP: It’s sort of like trying to boost my ego on how fast I may be and getting my 10 year-old out on the track and beating him. I’m like, ‘Yeah, I did it.’ I have maybe a year or two left of this. It doesn’t speak to that I’m fast; it speaks to him that he’s slow. And so the numbers for gemcitabine/cisplatin were very similar in the survival in both the squamous and the non-squamous patients, and they were both about 10 months. So, to me, to sort of de facto say that gemcitabine/cisplatin is all of a sudden a great regimen for squamous is a misnomer, and I don’t like when I hear that.

Talking about the Taxol aspect—carboplatin/paclitaxel—yes, it is amazing. That drug has stuck around for ages, hasn’t it? And your comment was, well, out in the community. Let’s not forget Dr. Schiller and a lot of these thought leaders designed this study, Dr. Belani Dr. Schiller. And so these are academic thought leaders who designed these studies, reported them at ASCO, and presented them in high-profile journals. So I would say the example was set from the top and has permeated to the bottom now.

Favorable reimbursement, favorable other things certainly have perpetuated that. I fight the same battle. I feel the exact same way. I don’t know why this drug continues to be used so often when we have these other alternatives, but it speaks to the fact that people still see very adequate tolerable side effects and activity.
                                                                                                                                                                                                                                                                                                                
Transcript Edited for Clarity
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