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Sequencing Decisions in Soft Tissue Sarcoma

Panelists:William D. Tap, MD, Memorial Sloan Kettering Cancer Center; Mark Agulnik, MD, Feinberg School of Medicine;George D. Demetri, MD, Dana-Farber Cancer Center;Martee L. Hensley, MD, Memorial Sloan Kettering Cancer Center; Shreyaskumar Patel, MD, The University of Texas MD Anderson Cancer Center;Damon Reed, MD, Moffitt Cancer Center
Published Online: Friday, Sep 02, 2016



Transcript:

William D. Tap, MD:
This has been a great discussion so far. And I think what’s been nice is we’ve really been outlining some of the agents we use in the frontline therapy: Adriamycin, Adriamycin/ifosfamide, gemcitabine/docetaxel. Now the question comes to, what do you do in a second-line setting? And I don’t want to just hear “what I didn’t do in the first-line setting.” How do you actually think about patients, and do you actually line things up from the beginning, saying, “I may use this first and have that as a second-line option?” Damon, what do you do?

Damon Reed, MD: So, as Martee excellently pointed out and gave us a construct for the cancer journey and palliation, rather than cure, what I tend to do is to consider the histology. I include all the therapies I would consider giving a patient and discuss all of them on a blank sheet of paper, starting with the agents, starting with the schedules, really practical things, and then major toxicities. I don’t think there are enough data right now to clearly say this is definitely what we should do in number 2, this is definitely what we should do number 3. And, rather, I’d like patients to have an understanding of, “Oh, there’s a wedding coming up and I would like something a little bit less toxic for these next couple months.” It really is a choice of order, rather than a strong prescription, that this has to be your next therapy. So, I think the discussion, based on the known toxicities, really helps guide patients, really helps patients anticipate and choose what makes the most sense for them.

William D. Tap, MD: Yes. And this is interesting, going back to one of George’s comments about how we break the rules, but it almost sounds like patients can be involved in helping you decide what therapies in what order. What do you guys think about it? How do you approach it?

Mark Agulnik, MD: Could we also plug clinical trials?

Damon Reed, MD: Of course.

Mark Agulnik, MD: This is our job. We’re academic physicians, and we’re academic oncologists. As we will move in to talking about all these new drugs that have come to market, none of these drugs would be on the market if it wasn’t for patients’ willingness to go into these clinical trials, whether or not they were with a placebo group. There’s always a fear of placebo, whether or not they were used with another agent, that may or may not have some degree of activity, but with an older agent. I think everybody listens and everybody watches TV. There are these great commercials now of all these great drugs that are not for their disease, and it has to be at one point for their disease. I think that as we do talk about all this and we offer them clinical trials, that is a very important message for them for first-line, for second-line, for third-line, and for fourth-line. But, certainly, exactly as you said, there is no ability to prescribe a medication without a conversation that really involves a frank discussion and really trying to figure out what do they want, what are their goals?

William D. Tap, MD: That’s great. And I love this journey, this race, or this marathon that we keep talking about. Any other thoughts?

Martee L. Hensley, MD: I take a very similar approach at the second- and third-line therapy conversation. And, as I’m talking, I also write on a piece of paper the name of the drug and two or three words about the schedule. For the women I take care of, it really matters whether they will or will not lose their hair; again, perhaps if it’s come back after being off first-line therapy for some time.

I do try to explain the concept of a RECIST response, particularly for second- or third-line drugs like pazopanib or trabectedin where objective response rates may be relatively low, but disease control rates might be relatively good. I want them to understand that if they go to Google and look for a response rate, and they find it too low to feel palatable to them, I want them to understand the concept of a progression-free survival, a concept of how long you can be on a tolerable drug for some time, feeling well, before you need to switch to the next thing. And the nice thing about writing things down is that they can keep that piece of paper, and say they chose B on that piece of paper, they know that those other choices are still out there. It’s very comforting for them to know that after second-line therapy, there’s going to be a next option to talk about.

George D. Demetri, MD: But this is the other rule we break, right? In pancreas cancer, virtually nobody makes it to fourth- or fifth-line therapy. I would say the majority of patients at our centers make it to fifth-, sixth-, seventh-line therapy, which is unusual. So, I think we all wind up doing the same thing. We make the big list. And I say to people, “Here, we have options.” And the issue for us is to decide together which of these options to use. We have options now in terms of schedule, oral, IV, things that fit their lifestyle, things that have certain benefits. And then, typically the patients will say, “You’ve seen a lot more of these than I have. I’m not making this decision alone.” I say, “No, but let’s make it together.” It’s the shared decision making that Paolo Casali in Italy always talks about.

William D. Tap, MD: I know, it’s true. And I’m finding, too, that more and more patients are coming with their own list, right? Because, with that information, that helps guide discussions, as well.

Mark Agulnik, MD: So, I’ll just say one thing. My worry, always, is the patient who doesn’t know better or can’t bring that list, and is someone that doesn’t have the list. I always worry about the two lines of therapy and hospice. That is always a worry for me, because you said we don’t have patients that don’t get four, five, or six lines of therapy; we just don’t see those patients. But, there are patients out there in the community that really stop after two, and that’s disheartening that there isn’t that better education out there.

William D. Tap, MD: Yes, I think so. There is a difference where there is this journey that we can continue to work with patients on, right? And I think that’s an important thing to understand. But, before we move on into some of these options, I just want to get an idea of how often you monitor patients. Do you start a regimen and you walk away, and 5 months later you come back? What do you do?

Mark Agulnik, MD: For the chemotherapeutics, I’m often doing every two cycles. As I get to the third- and fourth-line, depending on what the drug and the toxicity profile is, I usually then start to extend to three cycles, so 9 weeks typically. For the targeted agents, I typically do several months, sometimes 3 months. I try not to scan too early. I try to temper some of the expectations. I really try to allow someone to get a full try on these drugs.

Shreyaskumar Patel, MD: I think this is one area where what we write in clinical trials is indeed how we practice. Early on in the course of the therapy, we want to take a closer look to make sure that the efficacy/toxicity balance is still maintained in the patient’s favor. And as they get on cruise control mode, if you will, you can space out the scans. A comment I wanted to make about the previous conversation is that, again, this is probably more relevant to our colleagues in the community. The general principles we outlined for second-line and future-line therapies is absolutely correct, and there’s no disagreement. But, there are nuances about individual histologies that only we would know, and we are guilty of not publishing and writing everything up. And even if it’s there, it’s in some obscure thing that they can’t have access to, right?

So, it gets to the example of if it’s an angiosarcoma, don’t send them to the surgeon to cut it out. There are lots of different drugs, and we can try taxanes, for example. For the synovial sarcoma, for example, the gemcitabine/docetaxel experience doesn’t seem to be that great. Maybe what we end up with is pazopanib, which would be a good idea. I think those are the kinds of things where the word out there would be, pick up the phone and call your local consultant, if you will, right? We can frequently guide you in terms of what may be a better strategy or a better sequence, recognizing that sometimes you end up going through the whole sequence for one reason or another.

William D. Tap, MD: And I’ll say, not only a phone call, but have the patient visit. Because, I think any one of us can look at a patient for 5 seconds and say, “I know exactly what they’re able to tolerate or where we begin to gauge them.” Sometimes doing that over the phone can be very difficult, right? And we’ll talk about that a little bit later, too, because we’ll have to talk about how to manage toxicities.

Transcript Edited for Clarity

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Transcript:

William D. Tap, MD:
This has been a great discussion so far. And I think what’s been nice is we’ve really been outlining some of the agents we use in the frontline therapy: Adriamycin, Adriamycin/ifosfamide, gemcitabine/docetaxel. Now the question comes to, what do you do in a second-line setting? And I don’t want to just hear “what I didn’t do in the first-line setting.” How do you actually think about patients, and do you actually line things up from the beginning, saying, “I may use this first and have that as a second-line option?” Damon, what do you do?

Damon Reed, MD: So, as Martee excellently pointed out and gave us a construct for the cancer journey and palliation, rather than cure, what I tend to do is to consider the histology. I include all the therapies I would consider giving a patient and discuss all of them on a blank sheet of paper, starting with the agents, starting with the schedules, really practical things, and then major toxicities. I don’t think there are enough data right now to clearly say this is definitely what we should do in number 2, this is definitely what we should do number 3. And, rather, I’d like patients to have an understanding of, “Oh, there’s a wedding coming up and I would like something a little bit less toxic for these next couple months.” It really is a choice of order, rather than a strong prescription, that this has to be your next therapy. So, I think the discussion, based on the known toxicities, really helps guide patients, really helps patients anticipate and choose what makes the most sense for them.

William D. Tap, MD: Yes. And this is interesting, going back to one of George’s comments about how we break the rules, but it almost sounds like patients can be involved in helping you decide what therapies in what order. What do you guys think about it? How do you approach it?

Mark Agulnik, MD: Could we also plug clinical trials?

Damon Reed, MD: Of course.

Mark Agulnik, MD: This is our job. We’re academic physicians, and we’re academic oncologists. As we will move in to talking about all these new drugs that have come to market, none of these drugs would be on the market if it wasn’t for patients’ willingness to go into these clinical trials, whether or not they were with a placebo group. There’s always a fear of placebo, whether or not they were used with another agent, that may or may not have some degree of activity, but with an older agent. I think everybody listens and everybody watches TV. There are these great commercials now of all these great drugs that are not for their disease, and it has to be at one point for their disease. I think that as we do talk about all this and we offer them clinical trials, that is a very important message for them for first-line, for second-line, for third-line, and for fourth-line. But, certainly, exactly as you said, there is no ability to prescribe a medication without a conversation that really involves a frank discussion and really trying to figure out what do they want, what are their goals?

William D. Tap, MD: That’s great. And I love this journey, this race, or this marathon that we keep talking about. Any other thoughts?

Martee L. Hensley, MD: I take a very similar approach at the second- and third-line therapy conversation. And, as I’m talking, I also write on a piece of paper the name of the drug and two or three words about the schedule. For the women I take care of, it really matters whether they will or will not lose their hair; again, perhaps if it’s come back after being off first-line therapy for some time.

I do try to explain the concept of a RECIST response, particularly for second- or third-line drugs like pazopanib or trabectedin where objective response rates may be relatively low, but disease control rates might be relatively good. I want them to understand that if they go to Google and look for a response rate, and they find it too low to feel palatable to them, I want them to understand the concept of a progression-free survival, a concept of how long you can be on a tolerable drug for some time, feeling well, before you need to switch to the next thing. And the nice thing about writing things down is that they can keep that piece of paper, and say they chose B on that piece of paper, they know that those other choices are still out there. It’s very comforting for them to know that after second-line therapy, there’s going to be a next option to talk about.

George D. Demetri, MD: But this is the other rule we break, right? In pancreas cancer, virtually nobody makes it to fourth- or fifth-line therapy. I would say the majority of patients at our centers make it to fifth-, sixth-, seventh-line therapy, which is unusual. So, I think we all wind up doing the same thing. We make the big list. And I say to people, “Here, we have options.” And the issue for us is to decide together which of these options to use. We have options now in terms of schedule, oral, IV, things that fit their lifestyle, things that have certain benefits. And then, typically the patients will say, “You’ve seen a lot more of these than I have. I’m not making this decision alone.” I say, “No, but let’s make it together.” It’s the shared decision making that Paolo Casali in Italy always talks about.

William D. Tap, MD: I know, it’s true. And I’m finding, too, that more and more patients are coming with their own list, right? Because, with that information, that helps guide discussions, as well.

Mark Agulnik, MD: So, I’ll just say one thing. My worry, always, is the patient who doesn’t know better or can’t bring that list, and is someone that doesn’t have the list. I always worry about the two lines of therapy and hospice. That is always a worry for me, because you said we don’t have patients that don’t get four, five, or six lines of therapy; we just don’t see those patients. But, there are patients out there in the community that really stop after two, and that’s disheartening that there isn’t that better education out there.

William D. Tap, MD: Yes, I think so. There is a difference where there is this journey that we can continue to work with patients on, right? And I think that’s an important thing to understand. But, before we move on into some of these options, I just want to get an idea of how often you monitor patients. Do you start a regimen and you walk away, and 5 months later you come back? What do you do?

Mark Agulnik, MD: For the chemotherapeutics, I’m often doing every two cycles. As I get to the third- and fourth-line, depending on what the drug and the toxicity profile is, I usually then start to extend to three cycles, so 9 weeks typically. For the targeted agents, I typically do several months, sometimes 3 months. I try not to scan too early. I try to temper some of the expectations. I really try to allow someone to get a full try on these drugs.

Shreyaskumar Patel, MD: I think this is one area where what we write in clinical trials is indeed how we practice. Early on in the course of the therapy, we want to take a closer look to make sure that the efficacy/toxicity balance is still maintained in the patient’s favor. And as they get on cruise control mode, if you will, you can space out the scans. A comment I wanted to make about the previous conversation is that, again, this is probably more relevant to our colleagues in the community. The general principles we outlined for second-line and future-line therapies is absolutely correct, and there’s no disagreement. But, there are nuances about individual histologies that only we would know, and we are guilty of not publishing and writing everything up. And even if it’s there, it’s in some obscure thing that they can’t have access to, right?

So, it gets to the example of if it’s an angiosarcoma, don’t send them to the surgeon to cut it out. There are lots of different drugs, and we can try taxanes, for example. For the synovial sarcoma, for example, the gemcitabine/docetaxel experience doesn’t seem to be that great. Maybe what we end up with is pazopanib, which would be a good idea. I think those are the kinds of things where the word out there would be, pick up the phone and call your local consultant, if you will, right? We can frequently guide you in terms of what may be a better strategy or a better sequence, recognizing that sometimes you end up going through the whole sequence for one reason or another.

William D. Tap, MD: And I’ll say, not only a phone call, but have the patient visit. Because, I think any one of us can look at a patient for 5 seconds and say, “I know exactly what they’re able to tolerate or where we begin to gauge them.” Sometimes doing that over the phone can be very difficult, right? And we’ll talk about that a little bit later, too, because we’ll have to talk about how to manage toxicities.

Transcript Edited for Clarity
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