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Chemotherapy for Newly Diagnosed Squamous NSCLC

Panelists: Mark A. Socinski, MD, Florida Hospital Cancer Institute; Tracey L. Evans, MD, University of Pennsylvania; David M. Jackman, MD, Dana-Farber Cancer Institute; Edward S. Kim, MD, Levine Cancer Institute; Jared Weiss, MD, UNC Lineberger Comprehensive Cancer Center
Published: Wednesday, Mar 15, 2017



Transcript:

Mark Socinski, MD:
We’ve established PD-L1 testing as a standard of care. For the high expressors, we’ll use pembrolizumab. The reality of our lives is that most of those patients with squamous are not going to fall into that category. We have very little, or paucity, of any oncogenic driver situation. So, we’re stuck with chemotherapy for the time being. Dr. Evans, when you see a PD-L1-negative stage IV squamous patient in your practice, what’s your treatment paradigm?

Tracey L. Evans, MD: Well, I ask them how much they like their hair. That’s an important consideration when choosing what to give them, but it’s a standard of platinum-based chemotherapy. And for me, in the palliative setting, I use carboplatin. For squamous, I will combine that with either gemcitabine or a taxane. I do often use nab-paclitaxel as my taxane of choice, due to your study that showed the improvement in response rate. That was up to 40% for patients with squamous histology.

Mark Socinski, MD: Do you see that in your clinic?

Tracey L. Evans, MD: Do I see that the response rates are higher?

Mark Socinski, MD: Yes.

Tracey L. Evans, MD: I’m not sure. That’s hard for me to tell. I don’t think I really see a huge difference, but I do think the toxicity is more manageable. Actually, when that study came out, I was not a big convert. I thought, “This really isn’t new, this isn’t changing what I was doing before, and the drug costs a heck of a lot,” so I wasn’t a convert. But I had some experiences using nab-paclitaxel in later lines of therapy in people who couldn’t tolerate another taxane for various reasons—either ischemia or even a couple pneumonitis cases with docetaxel—but they responded. The patient begged me to give another taxane and I ended up using nab-paclitaxel. And it was through those experiences that it really does seem more tolerable, at least than docetaxel and probably more than Q3-week paclitaxel. But I also use a lot of weekly paclitaxel in order patients as well. And there, it might be similar. I’m not sure that the toxicities are that much more beneficial for nab-paclitaxel than for weekly paclitaxel.

Mark Socinski, MD: So, Jared, any different thoughts? What’s your practice pattern in first-line squamous, non–PD-L1 candidate, or positive?

Jared Weiss, MD: Many years ago, John Schiller taught us that the various doublets don’t seem particularly different from each other for the most part. And, of course, more recently, we’ve gotten some histology-specific data for both pemetrexed and nab-paclitaxel that we’ve spoken about. One thing I would add to this was your subgroup data on the elderly. So, in your carboplatin/paclitaxel versus carboplatin/nab-paclitaxel study, there was a near doubling of survival.

Mark Socinski, MD: Almost too good to believe.

Jared Weiss, MD: Almost too good to believe until it was followed up upon some by others. In your study, that was more than one-third of patients, right? It wasn’t some small subgroup; it was a rather substantive group. And at World Lung, Corey Langer released data on first a randomized phase II study of 2 different schedules of carboplatin and nab-paclitaxel. In the combined dataset, PFS was 6.2 months and OS was 14 .6 months, so maybe not quite the large number reached in your study, but still rather good compared to historic controls for the 70+ population. And I released data on nab-paclitaxel in the second line for a 70+ population that was 5.1 months of PFS and 9.6 months of OS in the second line—70+ PS 0 to 2, actually had real PS 2s on there. So, there may well be something to that story.

Tracey L. Evans, MD: Well, I think that speaks to the tolerability. In your study, there was an increased likelihood of the elderly patients to make it to second-line therapy if they got nab-paclitaxel as opposed to Q3-week paclitaxel. So, I think that that’s part of what’s going on.

Mark Socinski, MD: Yes, but this elderly thing keeps coming up, and we have no biomarker for albumin-bound paclitaxel. We have no idea if we can identify patients. Is there something different about elderly lung cancer than young lung cancer? I don’t know. There have been enough hints of this, but no definitive way to approach it. I’ve used a fair amount of nab-paclitaxel. I find the tolerability, and sometimes the schedule, is a bit of a determinant.

Tracey L. Evans, MD: I don’t follow your schedule.

Mark Socinski, MD: Oh, what do you do?

Tracey L. Evans, MD: Well, I do either 2 out of 3 or 3 out of 4.

Mark Socinski, MD: OK, alright. Fair enough.

Tracey L. Evans, MD: Usually, I start with 3 out of 4 and then I’ll drop. If I can’t, I’ll switch them to a 2 out of 3 schedule.

Jared Weiss, MD: Yes, and that’s what Dr Langer’s study explored. We don’t have data yet dividing out by the 2 schedules. But we should relatively soon.

Tracey L. Evans, MD: Yes, patients voted with their feet. They’re like, “Oh, I’m not coming back for the next one.” OK, take a week off.

Mark Socinski, MD: Yes. But I think nab-paclitaxel does have a role. I tend to use it in patients that either have heavier disease burden or are very symptomatic, thinking that this response rate is true, and, again, it was a blinded radiologic review independent from the study. And so, it was objectively assessed. But those are the patients that really need a response, and so I’ll use nab-paclitaxel in that setting. And, although Dr Schiller did suggest that all platinum-based doublets are created equal, there are some subsets based on histology that, in my mind, convinced me that I favor taxane-based therapy, unless the patient has a strong feeling about the side effect profile in that setting.

Jared Weiss, MD: Yes. The other nice thing about weekly therapy is you can check and drive a little bit more based on how the patient is going. So, prior to your data, I used a lot of weekly paclitaxel in older patients or more frail patients where they’re starting to get in trouble. You don’t have 3 or 4 weeks’ worth of drugs stuck in them, you have just 1 week. And you can adjust the dose, bail, give them a break, or whatever’s appropriate for that person.

Mark Socinski, MD: OK, I’m going to go right across the panel. For first-line squamous, good performance status, how many cycles do you give?

David M. Jackman, MD: I give 6 if they can tolerate it.

Jared Weiss, MD: I give 4.

Tracey L. Evans, MD: I give 4.

Edward S. Kim, MD: Did you say elderly or not?

Mark Socinski, MD: No, I didn’t bring in elderly, so just generally.

Edward S. Kim, MD: We do 4 and reassess at that point.

Tracey L. Evans, MD: We just changed our pathway. It used to be a 4 versus 6, but we put 4 in our pathway and I’m sticking to it.

Jared Weiss, MD: Do we know who generated that data?

Transcript Edited for Clarity

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Transcript:

Mark Socinski, MD:
We’ve established PD-L1 testing as a standard of care. For the high expressors, we’ll use pembrolizumab. The reality of our lives is that most of those patients with squamous are not going to fall into that category. We have very little, or paucity, of any oncogenic driver situation. So, we’re stuck with chemotherapy for the time being. Dr. Evans, when you see a PD-L1-negative stage IV squamous patient in your practice, what’s your treatment paradigm?

Tracey L. Evans, MD: Well, I ask them how much they like their hair. That’s an important consideration when choosing what to give them, but it’s a standard of platinum-based chemotherapy. And for me, in the palliative setting, I use carboplatin. For squamous, I will combine that with either gemcitabine or a taxane. I do often use nab-paclitaxel as my taxane of choice, due to your study that showed the improvement in response rate. That was up to 40% for patients with squamous histology.

Mark Socinski, MD: Do you see that in your clinic?

Tracey L. Evans, MD: Do I see that the response rates are higher?

Mark Socinski, MD: Yes.

Tracey L. Evans, MD: I’m not sure. That’s hard for me to tell. I don’t think I really see a huge difference, but I do think the toxicity is more manageable. Actually, when that study came out, I was not a big convert. I thought, “This really isn’t new, this isn’t changing what I was doing before, and the drug costs a heck of a lot,” so I wasn’t a convert. But I had some experiences using nab-paclitaxel in later lines of therapy in people who couldn’t tolerate another taxane for various reasons—either ischemia or even a couple pneumonitis cases with docetaxel—but they responded. The patient begged me to give another taxane and I ended up using nab-paclitaxel. And it was through those experiences that it really does seem more tolerable, at least than docetaxel and probably more than Q3-week paclitaxel. But I also use a lot of weekly paclitaxel in order patients as well. And there, it might be similar. I’m not sure that the toxicities are that much more beneficial for nab-paclitaxel than for weekly paclitaxel.

Mark Socinski, MD: So, Jared, any different thoughts? What’s your practice pattern in first-line squamous, non–PD-L1 candidate, or positive?

Jared Weiss, MD: Many years ago, John Schiller taught us that the various doublets don’t seem particularly different from each other for the most part. And, of course, more recently, we’ve gotten some histology-specific data for both pemetrexed and nab-paclitaxel that we’ve spoken about. One thing I would add to this was your subgroup data on the elderly. So, in your carboplatin/paclitaxel versus carboplatin/nab-paclitaxel study, there was a near doubling of survival.

Mark Socinski, MD: Almost too good to believe.

Jared Weiss, MD: Almost too good to believe until it was followed up upon some by others. In your study, that was more than one-third of patients, right? It wasn’t some small subgroup; it was a rather substantive group. And at World Lung, Corey Langer released data on first a randomized phase II study of 2 different schedules of carboplatin and nab-paclitaxel. In the combined dataset, PFS was 6.2 months and OS was 14 .6 months, so maybe not quite the large number reached in your study, but still rather good compared to historic controls for the 70+ population. And I released data on nab-paclitaxel in the second line for a 70+ population that was 5.1 months of PFS and 9.6 months of OS in the second line—70+ PS 0 to 2, actually had real PS 2s on there. So, there may well be something to that story.

Tracey L. Evans, MD: Well, I think that speaks to the tolerability. In your study, there was an increased likelihood of the elderly patients to make it to second-line therapy if they got nab-paclitaxel as opposed to Q3-week paclitaxel. So, I think that that’s part of what’s going on.

Mark Socinski, MD: Yes, but this elderly thing keeps coming up, and we have no biomarker for albumin-bound paclitaxel. We have no idea if we can identify patients. Is there something different about elderly lung cancer than young lung cancer? I don’t know. There have been enough hints of this, but no definitive way to approach it. I’ve used a fair amount of nab-paclitaxel. I find the tolerability, and sometimes the schedule, is a bit of a determinant.

Tracey L. Evans, MD: I don’t follow your schedule.

Mark Socinski, MD: Oh, what do you do?

Tracey L. Evans, MD: Well, I do either 2 out of 3 or 3 out of 4.

Mark Socinski, MD: OK, alright. Fair enough.

Tracey L. Evans, MD: Usually, I start with 3 out of 4 and then I’ll drop. If I can’t, I’ll switch them to a 2 out of 3 schedule.

Jared Weiss, MD: Yes, and that’s what Dr Langer’s study explored. We don’t have data yet dividing out by the 2 schedules. But we should relatively soon.

Tracey L. Evans, MD: Yes, patients voted with their feet. They’re like, “Oh, I’m not coming back for the next one.” OK, take a week off.

Mark Socinski, MD: Yes. But I think nab-paclitaxel does have a role. I tend to use it in patients that either have heavier disease burden or are very symptomatic, thinking that this response rate is true, and, again, it was a blinded radiologic review independent from the study. And so, it was objectively assessed. But those are the patients that really need a response, and so I’ll use nab-paclitaxel in that setting. And, although Dr Schiller did suggest that all platinum-based doublets are created equal, there are some subsets based on histology that, in my mind, convinced me that I favor taxane-based therapy, unless the patient has a strong feeling about the side effect profile in that setting.

Jared Weiss, MD: Yes. The other nice thing about weekly therapy is you can check and drive a little bit more based on how the patient is going. So, prior to your data, I used a lot of weekly paclitaxel in older patients or more frail patients where they’re starting to get in trouble. You don’t have 3 or 4 weeks’ worth of drugs stuck in them, you have just 1 week. And you can adjust the dose, bail, give them a break, or whatever’s appropriate for that person.

Mark Socinski, MD: OK, I’m going to go right across the panel. For first-line squamous, good performance status, how many cycles do you give?

David M. Jackman, MD: I give 6 if they can tolerate it.

Jared Weiss, MD: I give 4.

Tracey L. Evans, MD: I give 4.

Edward S. Kim, MD: Did you say elderly or not?

Mark Socinski, MD: No, I didn’t bring in elderly, so just generally.

Edward S. Kim, MD: We do 4 and reassess at that point.

Tracey L. Evans, MD: We just changed our pathway. It used to be a 4 versus 6, but we put 4 in our pathway and I’m sticking to it.

Jared Weiss, MD: Do we know who generated that data?

Transcript Edited for Clarity
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