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Tesetaxel in Doublet Therapy 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: So, I’ve been talking about sequential single-agent therapy forever and ever and ever. But every now and then I think about using a doublet, and those are patients who have significant disease burden, they have a lot of symptoms. How do you view the tesetaxel/capecitabine doublet as compared with others, for example, docetaxel/capecitabine? It’s not quite the same thing.

Joyce A. O’Shaughnessy, MD: We probably pretty reluctantly use a doublet normally when we really, really have to do. We really think there’s an absolute life-threatening situation. In NCCN [National Comprehensive Cancer Network] and ASCO [American Society of Clinical Oncology], it’s super clear that sequential single agents are the standard of care. You don’t get survival impact and you get more toxicity, but you have to use the doublets from time to time. But when you use a taxane with capecitabine and, of course, docetaxel—very familiar with, we did a big adjuvant trial with it as well—it is not a sustainable doublet nor is paclitaxel with capecitabine a sustainable doublet.

Andrew D. Seidman, MD: So, you can give 4, 6 cycles and then you’re needing to back off or stop one of the agents.

Joyce A. O’Shaughnessy, MD: Stop the IV [intravenous] usually is what we do. And oftentimes, that is successful for the patient. They will continue their progression-free survival [PFS]. However, unfortunately, I’ve had a number of occasions where you stop the IV and that was the agent that was really helping the patient, and then their disease progresses again. So, certainly, it would be ideal to have a well-tolerated doublet for those patients who you need doublet therapy for. And if we had a well-tolerated doublet with a substantially better PFS, then we would consider utilizing that, provided it wasn’t substantially more toxicity. But it would be great to have a doublet where the efficacy was excellent but the tolerability was such that you could continue that indefinitely.

Andrew D. Seidman, MD: Right, so you don’t run into limiting neuropathy, fatigue, low incidence of febrile neutropenia, etc.

Joyce A. O’Shaughnessy, MD: Exactly, and this incredible asthenia that builds up over time, nail-bed changes that are very, very difficult with docetaxel. You get the anasarca that’s absolutely treatment-limiting. There’s a number of treatment-limiting issues with regard to the taxanes.

Andrew D. Seidman, MD: So, in a sense, because these are ER-positive patients emerging from endocrine therapy and receiving either capecitabine or tesetaxel/capecitabine, tesetaxel/capecitabine in this trial isn’t the thing you need when your back is against the wall necessarily. It’s not a doublet when I need a response and I need it right away.

Joyce A. O’Shaughnessy, MD: Right. And we’re participating in the CONTESSA trial and that’s what I’m doing, Andy. Whenever I would be giving a woman capecitabine and she has got measurable disease, as the trial requires, I just automatically say, “Hey, let’s look at this trial for you.”

Andrew D. Seidman, MD: We are participating and I’m making it my chief goal to put more patients on the trial than you and your group. That’s a big challenge.

Joyce A. O’Shaughnessy, MD: But, yes, that’s the hope that we’ll build something more effective, longer-acting, durable, without treatment-limiting toxicities that we can then have as an option for certain patients.

Andrew D. Seidman, MD: Important distinction to make.

Transcript Edited for Clarity 

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Transcript: 

Andrew D. Seidman, MD: So, I’ve been talking about sequential single-agent therapy forever and ever and ever. But every now and then I think about using a doublet, and those are patients who have significant disease burden, they have a lot of symptoms. How do you view the tesetaxel/capecitabine doublet as compared with others, for example, docetaxel/capecitabine? It’s not quite the same thing.

Joyce A. O’Shaughnessy, MD: We probably pretty reluctantly use a doublet normally when we really, really have to do. We really think there’s an absolute life-threatening situation. In NCCN [National Comprehensive Cancer Network] and ASCO [American Society of Clinical Oncology], it’s super clear that sequential single agents are the standard of care. You don’t get survival impact and you get more toxicity, but you have to use the doublets from time to time. But when you use a taxane with capecitabine and, of course, docetaxel—very familiar with, we did a big adjuvant trial with it as well—it is not a sustainable doublet nor is paclitaxel with capecitabine a sustainable doublet.

Andrew D. Seidman, MD: So, you can give 4, 6 cycles and then you’re needing to back off or stop one of the agents.

Joyce A. O’Shaughnessy, MD: Stop the IV [intravenous] usually is what we do. And oftentimes, that is successful for the patient. They will continue their progression-free survival [PFS]. However, unfortunately, I’ve had a number of occasions where you stop the IV and that was the agent that was really helping the patient, and then their disease progresses again. So, certainly, it would be ideal to have a well-tolerated doublet for those patients who you need doublet therapy for. And if we had a well-tolerated doublet with a substantially better PFS, then we would consider utilizing that, provided it wasn’t substantially more toxicity. But it would be great to have a doublet where the efficacy was excellent but the tolerability was such that you could continue that indefinitely.

Andrew D. Seidman, MD: Right, so you don’t run into limiting neuropathy, fatigue, low incidence of febrile neutropenia, etc.

Joyce A. O’Shaughnessy, MD: Exactly, and this incredible asthenia that builds up over time, nail-bed changes that are very, very difficult with docetaxel. You get the anasarca that’s absolutely treatment-limiting. There’s a number of treatment-limiting issues with regard to the taxanes.

Andrew D. Seidman, MD: So, in a sense, because these are ER-positive patients emerging from endocrine therapy and receiving either capecitabine or tesetaxel/capecitabine, tesetaxel/capecitabine in this trial isn’t the thing you need when your back is against the wall necessarily. It’s not a doublet when I need a response and I need it right away.

Joyce A. O’Shaughnessy, MD: Right. And we’re participating in the CONTESSA trial and that’s what I’m doing, Andy. Whenever I would be giving a woman capecitabine and she has got measurable disease, as the trial requires, I just automatically say, “Hey, let’s look at this trial for you.”

Andrew D. Seidman, MD: We are participating and I’m making it my chief goal to put more patients on the trial than you and your group. That’s a big challenge.

Joyce A. O’Shaughnessy, MD: But, yes, that’s the hope that we’ll build something more effective, longer-acting, durable, without treatment-limiting toxicities that we can then have as an option for certain patients.

Andrew D. Seidman, MD: Important distinction to make.

Transcript Edited for Clarity 
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