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Combining Chemotherapy & Immunotherapy in Squamous NSCLC

Panelists: Leora Horn, MD, MSc, FRCPC, Vanderbilt University Medical Center; Edward B. Garon, MD, David Geffen School of Medicine at UCLA; Thomas E. Stinchcombe, MD, Duke Cancer Institute
Published: Tuesday, Oct 16, 2018



Transcript: 

Leora Horn, MD, MSc, FRCPC: Moving from nonsquamous to squamous non–small cell lung cancer, we’ve had 2 trials come out in the past 6 months. We had KEYNOTE-407, which looked at carboplatin/nab-paclitaxel with or without pembrolizumab, and then we had the IMpower131 data that looked at carboplatin with a taxane—paclitaxel or nab-paclitaxel—with or without atezolizumab. So we have 2 studies with very similar patient populations. How have those trials affected how you’re treating your patients with squamous cell lung cancer in the first-line setting?

Edward B. Garon, MD: I think this is another situation where we’re sort of waiting for regulatory approval. That said, there is a difference. As hesitant as I have been to look at cross-trial comparisons and other study settings, here we have data from the KEYNOTE-407 study that shows a progression-free survival benefit and overall survival benefit. In the IMpower131 study, there was a strong progression-free survival benefit but there was not a survival benefit. There was not a particularly strong signal in favor of survival. How that happens is a little unclear to me. I don’t entirely understand how you could have such an impressive progression-free survival benefit without an overall survival benefit. In this setting, with regulatory approval, I would be inclined, with both regimens, to use the KEYNOTE-407 data. Just as Tom said, my preferred regimen in the EGFR-mutant patients would be the one where there is actually data revealing clear benefit. Here, the presence versus absence of a survival benefit between these 2 would lead me to choose the one that has shown survival benefit, which is the carboplatin/paclitaxel regimen—either standard paclitaxel or nab-paclitaxel—plus pembrolizumab.

Leora Horn, MD, MSc, FRCPC: And maybe with time we’ll get some of that survival data. It was definitely an immature or interim analysis for progression-free survival. Maybe we will see some of that survival data come out with time. Are you doing anything different, Tom?

Thomas E. Stinchcombe, MD: I’ve actually adopted the carboplatin/taxane/pembrolizumab regimen. Some of the insurance companies don’t want to pay for it, but, for the squamous patients, it’s been so staggering in our care. This is a trial that’s been published and peer-reviewed. I’m hopeful that this will help improve the care for those patients.

Leora Horn, MD, MSc, FRCPC: And it is in the NCCN [National Comprehensive Cancer Network] guidelines, so that does make it a bit more available to patients. Before this data came out, I was using a lot of platinum and gemcitabine in my squamous cell patients. Sometimes I get calls from the community saying, “Will you do this? Should I give carboplatin, gemcitabine, and pembrolizumab?” I have said “no.” I don’t know if you’ve tried that or done anything like that?

Thomas E. Stinchcombe, MD: My inclination would be to say no. I think that you should use the combination that showed a benefit.

Edward B. Garon, MD: The other thing that I would add is that I’ve found it sort of sobering how poorly we’ve been able to predict where toxicity would be seen with these combinations. There certainly are small studies using gemcitabine, but, whether there can be a signal in a large study, I’d like to see the large study before I’d be comfortable recommending it to people.

Leora Horn, MD, MSc, FRCPC: Yes, absolutely. One of the unique toxicities that we saw with KEYNOTE-189 was nephritis. My bias has said that it’s more of a pemetrexed phenomenon; not necessarily the platinum agent. So yes, we definitely have to be careful.

Transcript Edited for Clarity
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Transcript: 

Leora Horn, MD, MSc, FRCPC: Moving from nonsquamous to squamous non–small cell lung cancer, we’ve had 2 trials come out in the past 6 months. We had KEYNOTE-407, which looked at carboplatin/nab-paclitaxel with or without pembrolizumab, and then we had the IMpower131 data that looked at carboplatin with a taxane—paclitaxel or nab-paclitaxel—with or without atezolizumab. So we have 2 studies with very similar patient populations. How have those trials affected how you’re treating your patients with squamous cell lung cancer in the first-line setting?

Edward B. Garon, MD: I think this is another situation where we’re sort of waiting for regulatory approval. That said, there is a difference. As hesitant as I have been to look at cross-trial comparisons and other study settings, here we have data from the KEYNOTE-407 study that shows a progression-free survival benefit and overall survival benefit. In the IMpower131 study, there was a strong progression-free survival benefit but there was not a survival benefit. There was not a particularly strong signal in favor of survival. How that happens is a little unclear to me. I don’t entirely understand how you could have such an impressive progression-free survival benefit without an overall survival benefit. In this setting, with regulatory approval, I would be inclined, with both regimens, to use the KEYNOTE-407 data. Just as Tom said, my preferred regimen in the EGFR-mutant patients would be the one where there is actually data revealing clear benefit. Here, the presence versus absence of a survival benefit between these 2 would lead me to choose the one that has shown survival benefit, which is the carboplatin/paclitaxel regimen—either standard paclitaxel or nab-paclitaxel—plus pembrolizumab.

Leora Horn, MD, MSc, FRCPC: And maybe with time we’ll get some of that survival data. It was definitely an immature or interim analysis for progression-free survival. Maybe we will see some of that survival data come out with time. Are you doing anything different, Tom?

Thomas E. Stinchcombe, MD: I’ve actually adopted the carboplatin/taxane/pembrolizumab regimen. Some of the insurance companies don’t want to pay for it, but, for the squamous patients, it’s been so staggering in our care. This is a trial that’s been published and peer-reviewed. I’m hopeful that this will help improve the care for those patients.

Leora Horn, MD, MSc, FRCPC: And it is in the NCCN [National Comprehensive Cancer Network] guidelines, so that does make it a bit more available to patients. Before this data came out, I was using a lot of platinum and gemcitabine in my squamous cell patients. Sometimes I get calls from the community saying, “Will you do this? Should I give carboplatin, gemcitabine, and pembrolizumab?” I have said “no.” I don’t know if you’ve tried that or done anything like that?

Thomas E. Stinchcombe, MD: My inclination would be to say no. I think that you should use the combination that showed a benefit.

Edward B. Garon, MD: The other thing that I would add is that I’ve found it sort of sobering how poorly we’ve been able to predict where toxicity would be seen with these combinations. There certainly are small studies using gemcitabine, but, whether there can be a signal in a large study, I’d like to see the large study before I’d be comfortable recommending it to people.

Leora Horn, MD, MSc, FRCPC: Yes, absolutely. One of the unique toxicities that we saw with KEYNOTE-189 was nephritis. My bias has said that it’s more of a pemetrexed phenomenon; not necessarily the platinum agent. So yes, we definitely have to be careful.

Transcript Edited for Clarity
View Conference Coverage
Online CME Activities
TitleExpiration DateCME Credits
Community Practice Connections™: Oncology Best Practice™ Decision Points in Advanced NSCLC: Assessing Treatment Options Beyond Disease ProgressionNov 30, 20181.0
Community Practice Connections™: Precision Medicine for Community Oncologists: Assessing the Role of Tumor-Testing Technologies in Cancer CareNov 30, 20181.0
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