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Optimizing Selection of Chemotherapy for HR+ mBC

Panelists: Joyce A. OShaughnessy, MD, Baylor-Sammons Cancer Center; Andrew D. Seidman, MD, Memorial Sloan Kettering Cancer Center
Published: Tuesday, Dec 04, 2018



Transcript: 

Andrew D. Seidman, MD: For the patient who you feel maybe capecitabine isn’t enough, maybe her disease isn’t so bad that she requires doublet therapy, when you’re thinking about single agents, for me in my practice, many of these patients have never experienced hair loss and that can be a factor. I don’t know, how does patient preference drive your decisions here?

Joyce A. O’Shaughnessy, MD: Very much. Hair loss I think, of course, is hugely disappointing to patients. There are some who certainly will decline alopecia-inducing chemotherapy. Thankfully, we have options for those patients. That’s often times when I’ll use the vinorelbine alone or with capecitabine. But we also have patients, Andy, who come in with antecedent neuropathy. They’ve had neuropathy from their adjuvant taxane, they have a history of skin rash from taxanes, or they have had a history of myelosuppression, so you’re very concerned about bone marrow, etc. So, thankfully, we have a choice among the taxanes. I know a lot of doctors do utilize taxanes even for their first-line endocrine therapy-resistant patient. A lot of doctors will go on to taxanes. How do you think about that, do you ever use a taxane over capecitabine? Which taxane do you tend to use in the metastatic setting?

Andrew D. Seidman, MD: Yes, so I like to go to capecitabine absolutely as first-line therapy. The patients where I would say I shy away from it tend to have a higher disease burden and more symptoms. Then I would probably lead with paclitaxel. And this guy named Seidman described the fact that weekly paclitaxel is more effective than every 3 weeks. So, that tends to be my default regimen. I tend to give weekly paclitaxel. For patients who truly are just adamant about not wanting to lose their hair, I will give, most commonly, vinorelbine as an alternative.

Joyce A. O’Shaughnessy, MD: Which is really a very effective drug. Yes, I remember when your initial phase II data came out. I remember thinking with the weekly paclitaxel, it just changed practice; remarkably impactful data set.

Andrew D. Seidman, MD: Thank you very much, Joyce.

Joyce A. O’Shaughnessy, MD: It was, really. I remember, wow, wow, what a change in practice because then you went on to a randomized trial. But the initial data were phase II and were very impactful.

Andrew D. Seidman, MD: Before we transition to talk about oral taxanes, I do want to just touch on the visceral crisis patient. So, that patient is probably not going to get capecitabine. They may not even get a single-agent taxane. We’ve got docetaxel/capecitabine as an FDA-approved doublet, we’ve got paclitaxel/gemcitabine as an FDA-approved doublet. One can think of other things to do. So, when do you go to doublets in these patients and what doublets do you think about?

Joyce A. O’Shaughnessy, MD: I recently had 2 very similar patients who had aggressive, highly proliferative grade 3 ER [estrogen receptor]-positive disease in the primary breast cancers who received maximum chemotherapy and AI [aromatase inhibitor] therapy. And then when they recurred, relatively short disease-free interval of under 3 years on AI therapy with liver full of cancer and abnormal LFTs [liver function tests]. Whoa, and I have 2 of these patients, both of them happen to be on vinorelbine plus capecitabine because of my experience. I can tell for both of those patients, I don’t want to stop either drug. And so, the problem with a taxane and capecitabine combination over time as a doublet, you can get these nail-bed changes where you think, “I’ve had patients completely lose their nails permanently.”

Andrew D. Seidman, MD: Our patients are putting their fingers in ice in the infusion rooms now.

Joyce A. O’Shaughnessy, MD: Yes, we do the same, and that may help. But, oftentimes, if I feel like I just want to get good cytoreduction then stop the IV [intravenous] agent and continue with the capecitabine, then I will go to docetaxel or there has been a lot of work, as well, done with the weekly paclitaxel with capecitabine. Sometimes I like to avoid the steroid, the dexamethasone. If I’m going to use a single-agent taxane, I’ll often use nab-paclitaxel because it’s going to be a long duration of therapy. I’m going to try to avoid the adrenal suppression because people get increasingly fatigued, and so I will use the nab-paclitaxel.

Andrew D. Seidman, MD: And I always think backwards to when I finished my fellowship training 26 years ago and paclitaxel was emerging. And there was this drug that we were giving in the hospital as a 24-hour infusion with pre-medications, steroids, antihistamines. And if at that moment there was another product called nanoparticle albumin-bound paclitaxel that didn’t require pre-medications, that was without that risk of hypersensitivity reactions, which drug would have been the blockbuster drug at that time? So, it’s an interesting accent of history.

Transcript Edited for Clarity 

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Transcript: 

Andrew D. Seidman, MD: For the patient who you feel maybe capecitabine isn’t enough, maybe her disease isn’t so bad that she requires doublet therapy, when you’re thinking about single agents, for me in my practice, many of these patients have never experienced hair loss and that can be a factor. I don’t know, how does patient preference drive your decisions here?

Joyce A. O’Shaughnessy, MD: Very much. Hair loss I think, of course, is hugely disappointing to patients. There are some who certainly will decline alopecia-inducing chemotherapy. Thankfully, we have options for those patients. That’s often times when I’ll use the vinorelbine alone or with capecitabine. But we also have patients, Andy, who come in with antecedent neuropathy. They’ve had neuropathy from their adjuvant taxane, they have a history of skin rash from taxanes, or they have had a history of myelosuppression, so you’re very concerned about bone marrow, etc. So, thankfully, we have a choice among the taxanes. I know a lot of doctors do utilize taxanes even for their first-line endocrine therapy-resistant patient. A lot of doctors will go on to taxanes. How do you think about that, do you ever use a taxane over capecitabine? Which taxane do you tend to use in the metastatic setting?

Andrew D. Seidman, MD: Yes, so I like to go to capecitabine absolutely as first-line therapy. The patients where I would say I shy away from it tend to have a higher disease burden and more symptoms. Then I would probably lead with paclitaxel. And this guy named Seidman described the fact that weekly paclitaxel is more effective than every 3 weeks. So, that tends to be my default regimen. I tend to give weekly paclitaxel. For patients who truly are just adamant about not wanting to lose their hair, I will give, most commonly, vinorelbine as an alternative.

Joyce A. O’Shaughnessy, MD: Which is really a very effective drug. Yes, I remember when your initial phase II data came out. I remember thinking with the weekly paclitaxel, it just changed practice; remarkably impactful data set.

Andrew D. Seidman, MD: Thank you very much, Joyce.

Joyce A. O’Shaughnessy, MD: It was, really. I remember, wow, wow, what a change in practice because then you went on to a randomized trial. But the initial data were phase II and were very impactful.

Andrew D. Seidman, MD: Before we transition to talk about oral taxanes, I do want to just touch on the visceral crisis patient. So, that patient is probably not going to get capecitabine. They may not even get a single-agent taxane. We’ve got docetaxel/capecitabine as an FDA-approved doublet, we’ve got paclitaxel/gemcitabine as an FDA-approved doublet. One can think of other things to do. So, when do you go to doublets in these patients and what doublets do you think about?

Joyce A. O’Shaughnessy, MD: I recently had 2 very similar patients who had aggressive, highly proliferative grade 3 ER [estrogen receptor]-positive disease in the primary breast cancers who received maximum chemotherapy and AI [aromatase inhibitor] therapy. And then when they recurred, relatively short disease-free interval of under 3 years on AI therapy with liver full of cancer and abnormal LFTs [liver function tests]. Whoa, and I have 2 of these patients, both of them happen to be on vinorelbine plus capecitabine because of my experience. I can tell for both of those patients, I don’t want to stop either drug. And so, the problem with a taxane and capecitabine combination over time as a doublet, you can get these nail-bed changes where you think, “I’ve had patients completely lose their nails permanently.”

Andrew D. Seidman, MD: Our patients are putting their fingers in ice in the infusion rooms now.

Joyce A. O’Shaughnessy, MD: Yes, we do the same, and that may help. But, oftentimes, if I feel like I just want to get good cytoreduction then stop the IV [intravenous] agent and continue with the capecitabine, then I will go to docetaxel or there has been a lot of work, as well, done with the weekly paclitaxel with capecitabine. Sometimes I like to avoid the steroid, the dexamethasone. If I’m going to use a single-agent taxane, I’ll often use nab-paclitaxel because it’s going to be a long duration of therapy. I’m going to try to avoid the adrenal suppression because people get increasingly fatigued, and so I will use the nab-paclitaxel.

Andrew D. Seidman, MD: And I always think backwards to when I finished my fellowship training 26 years ago and paclitaxel was emerging. And there was this drug that we were giving in the hospital as a 24-hour infusion with pre-medications, steroids, antihistamines. And if at that moment there was another product called nanoparticle albumin-bound paclitaxel that didn’t require pre-medications, that was without that risk of hypersensitivity reactions, which drug would have been the blockbuster drug at that time? So, it’s an interesting accent of history.

Transcript Edited for Clarity 
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