ONCAlert | Upfront Therapy for mRCC

Case 1: Bevacizumab in Stage IV Ovarian Cancer

Targeted Oncology
Published Online:1:07 PM, Thu May 23, 2019


EXPERT PERSPECTIVE VIRTUAL TUMOR BOARD

Robert L. Coleman, MD: Okay, so now we have a patient and we’ve come up with a surgical plan. Let’s say we decide to go with a neoadjuvant approach, even though Dave really wanted to operate on her. What’s our chemotherapy choice?

Susana M. Campos, MD, MPH: Chemotherapy regimen?

Robert L. Coleman, MD: Yes, what do we do?

Susana M. Campos, MD, MPH: We have many different data. We’ve looked at ICON8. We’ve looked at GOG 262. We looked at GOG 0218 and ICON7. At the end of the day, it really boils down to a paclitaxel and carboplatin. The question of bevacizumab is a good question here. We have a 44-year-old, stage IV, high-risk, generally healthy individual. So we would ask ourselves the question: Is this the person for whom you might want to incorporate bevacizumab? And if you did, what data could you draw on to actually substantiate that opinion?

This was a good question, to be honest. If you look at GOG 0218 and ICON7, we had a progression-free survival benefit in GOG 0218. But if you look at more of the modified ICON7, and looked at specific cohorts — for example, suboptimally debulked stage patients, all stage IV patients — they had a concomitant patient population of about 502 patients. And they did actually see a benefit of bevacizumab in that cohort.

So here you have a 44-year-old woman who was young with no other comorbidities, by presumptions, for whom we’re going to undergo neoadjuvant therapy despite the fact that maybe there’s a difference of opinion.

David O’Malley, MD: I can’t argue that.

Susana M. Campos, , MPH: Would you give her the benefit of the doubt of putting her on bevacizumab, relying and leaning on the data of the modified ICON7 trial? I don’t think it’s unreasonable if it’s done right.

David O’Malley, MD: The problem in the United States is it’s not approved unless they’ve had surgery. So I think for those patients, I’m more apt to start the doublet. And then, if they’re not responding or their ascites isn’t drying up, then it may potentially be appealing to have that approved. So normally when we do that with neoadjuvant, then we’re going to bring the bevacizumab in afterward.

Susana M. Campos, MD, MPH: I agree. It gets very complicated, in terms of when to start, when to hold. And how many cycles are you really giving in the neoadjuvant setting?

Robert L. Coleman, : That was my next question.

Susana M. Campos, MD, MPH: At the end of the day, you’re really looking at 1 or 2 cycles. You might find yourself in more complications than it’s worth.

Shannon N. Westin, MD: I like what Dave said. I do that often, where I start the chemotherapy and then, if I’m not seeing the benefit that I want, maybe add the bevacizumab. And I would just add the subanalysis of GOG 0218 was pretty compelling where you saw that the stage IVs looked similar to stage IIIs, in those patients who received the bevacizumab, as far as survival was concerned. But still, you’re looking for something to help guide your decision.

David O’Malley, MD: That is really a very important point. You have to give time after the bevacizumab before you take them to surgery, and make sure you’re holding that prior to the cycle. I really like to give them 8 weeks without bevacizumab, but I think 6 weeks is probably more realistic.

Shannon N. Westin, MD: Yes, especially with the every-3-week dosing.

Robert L. Coleman, MD: Right. So how many cycles before, and how many cycles after?

Shannon N. Westin, MD: I generally give 3. But you know, certainly 3 to 4 is reasonable. At that point, you want to take a look. You want to see if you’re getting any benefit. If you’re getting past 3 or 4 and you’re still not going to be able to take that patient to surgery, the chance that she’s going to have a good outcome has really been diminished.

Robert L. Coleman, MD: In our database, when we look at the 3 versus the 6, there wasn’t as much of a difference as I had thought there was going to be.

Shannon N. Westin, MD: No, there wasn’t as much, but there was a slight difference. In some other retrospective studies, it’s been a significant difference.

Gregory Riedlinger, MD, PhD: That’s right. Dr Nicoletta Colombo did this nice study and actually looked at the number of cycles, pre, and basically showed that there was this kind of law of diminishing returns. The more pre-cycles that you gave, the less well the patients did. But some of that’s also selection, right? Because the patients who immediately respond, you take the surgery after 3.

David O’Malley, MD: Well, somewhat selection, but a take home point is unless there’s a reason, 3 to 4 cycles prior surgery. You know? We’re seeing a lot of our patients in consult but they’re already ….

Robert L. Coleman, MD: They’ve already had it.

David O’Malley, MD: And so, your options are really limited. They have to be evaluated by a gynecologic oncologist prior to the 3 to 4 cycles to get the interval debulking.

Susana M. Campos, MD, MPH: After the 3 to 4 cycles, what do you use, as a surgeon? What criteria do you use in terms of taking them to surgery? We look at chemotherapy responsiveness. That’s first and foremost. But are there any other criteria? Do you look at CA 125 [cancer antigen 125] trends and the like?

Shannon N. Westin, MD: I think you look at the whole ….

Susana M. Campos, MD, MPH: The whole picture, yes.

Shannon N. Westin, MD: We tend to use a lot of RECIST [response evaluation criteria in solid tumors], just because that’s what we do with all of the other trials. And so we are using that type of idea, but that can be difficult because sometimes it’s just that peritoneal carcinomatosis that’s not really measurable. So you just have to get a sense of, why didn’t you take her to surgery up front? And are those problems gone now? So if it was a performance status issue, how does she look in front of you right now? If it was disease location, have things shrunk? Have they shrunk enough? Is there still quite a bit of disease that would be residual after surgery? Let’s say they had bulky adenopathy in the mediastinum. When do you take that patient to surgery?

But those are the kinds of things you have to weigh when trying to decide.

Susana M. Campos, MD, MPH: Absolutely, yes.

Transcript edited for clarity.


EXPERT PERSPECTIVE VIRTUAL TUMOR BOARD

Robert L. Coleman, MD: Okay, so now we have a patient and we’ve come up with a surgical plan. Let’s say we decide to go with a neoadjuvant approach, even though Dave really wanted to operate on her. What’s our chemotherapy choice?

Susana M. Campos, MD, MPH: Chemotherapy regimen?

Robert L. Coleman, MD: Yes, what do we do?

Susana M. Campos, MD, MPH: We have many different data. We’ve looked at ICON8. We’ve looked at GOG 262. We looked at GOG 0218 and ICON7. At the end of the day, it really boils down to a paclitaxel and carboplatin. The question of bevacizumab is a good question here. We have a 44-year-old, stage IV, high-risk, generally healthy individual. So we would ask ourselves the question: Is this the person for whom you might want to incorporate bevacizumab? And if you did, what data could you draw on to actually substantiate that opinion?

This was a good question, to be honest. If you look at GOG 0218 and ICON7, we had a progression-free survival benefit in GOG 0218. But if you look at more of the modified ICON7, and looked at specific cohorts — for example, suboptimally debulked stage patients, all stage IV patients — they had a concomitant patient population of about 502 patients. And they did actually see a benefit of bevacizumab in that cohort.

So here you have a 44-year-old woman who was young with no other comorbidities, by presumptions, for whom we’re going to undergo neoadjuvant therapy despite the fact that maybe there’s a difference of opinion.

David O’Malley, MD: I can’t argue that.

Susana M. Campos, , MPH: Would you give her the benefit of the doubt of putting her on bevacizumab, relying and leaning on the data of the modified ICON7 trial? I don’t think it’s unreasonable if it’s done right.

David O’Malley, MD: The problem in the United States is it’s not approved unless they’ve had surgery. So I think for those patients, I’m more apt to start the doublet. And then, if they’re not responding or their ascites isn’t drying up, then it may potentially be appealing to have that approved. So normally when we do that with neoadjuvant, then we’re going to bring the bevacizumab in afterward.

Susana M. Campos, MD, MPH: I agree. It gets very complicated, in terms of when to start, when to hold. And how many cycles are you really giving in the neoadjuvant setting?

Robert L. Coleman, : That was my next question.

Susana M. Campos, MD, MPH: At the end of the day, you’re really looking at 1 or 2 cycles. You might find yourself in more complications than it’s worth.

Shannon N. Westin, MD: I like what Dave said. I do that often, where I start the chemotherapy and then, if I’m not seeing the benefit that I want, maybe add the bevacizumab. And I would just add the subanalysis of GOG 0218 was pretty compelling where you saw that the stage IVs looked similar to stage IIIs, in those patients who received the bevacizumab, as far as survival was concerned. But still, you’re looking for something to help guide your decision.

David O’Malley, MD: That is really a very important point. You have to give time after the bevacizumab before you take them to surgery, and make sure you’re holding that prior to the cycle. I really like to give them 8 weeks without bevacizumab, but I think 6 weeks is probably more realistic.

Shannon N. Westin, MD: Yes, especially with the every-3-week dosing.

Robert L. Coleman, MD: Right. So how many cycles before, and how many cycles after?

Shannon N. Westin, MD: I generally give 3. But you know, certainly 3 to 4 is reasonable. At that point, you want to take a look. You want to see if you’re getting any benefit. If you’re getting past 3 or 4 and you’re still not going to be able to take that patient to surgery, the chance that she’s going to have a good outcome has really been diminished.

Robert L. Coleman, MD: In our database, when we look at the 3 versus the 6, there wasn’t as much of a difference as I had thought there was going to be.

Shannon N. Westin, MD: No, there wasn’t as much, but there was a slight difference. In some other retrospective studies, it’s been a significant difference.

Gregory Riedlinger, MD, PhD: That’s right. Dr Nicoletta Colombo did this nice study and actually looked at the number of cycles, pre, and basically showed that there was this kind of law of diminishing returns. The more pre-cycles that you gave, the less well the patients did. But some of that’s also selection, right? Because the patients who immediately respond, you take the surgery after 3.

David O’Malley, MD: Well, somewhat selection, but a take home point is unless there’s a reason, 3 to 4 cycles prior surgery. You know? We’re seeing a lot of our patients in consult but they’re already ….

Robert L. Coleman, MD: They’ve already had it.

David O’Malley, MD: And so, your options are really limited. They have to be evaluated by a gynecologic oncologist prior to the 3 to 4 cycles to get the interval debulking.

Susana M. Campos, MD, MPH: After the 3 to 4 cycles, what do you use, as a surgeon? What criteria do you use in terms of taking them to surgery? We look at chemotherapy responsiveness. That’s first and foremost. But are there any other criteria? Do you look at CA 125 [cancer antigen 125] trends and the like?

Shannon N. Westin, MD: I think you look at the whole ….

Susana M. Campos, MD, MPH: The whole picture, yes.

Shannon N. Westin, MD: We tend to use a lot of RECIST [response evaluation criteria in solid tumors], just because that’s what we do with all of the other trials. And so we are using that type of idea, but that can be difficult because sometimes it’s just that peritoneal carcinomatosis that’s not really measurable. So you just have to get a sense of, why didn’t you take her to surgery up front? And are those problems gone now? So if it was a performance status issue, how does she look in front of you right now? If it was disease location, have things shrunk? Have they shrunk enough? Is there still quite a bit of disease that would be residual after surgery? Let’s say they had bulky adenopathy in the mediastinum. When do you take that patient to surgery?

But those are the kinds of things you have to weigh when trying to decide.

Susana M. Campos, MD, MPH: Absolutely, yes.

Transcript edited for clarity.
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