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Anthracycline-Based Regimens: Perioperative Setting for TNBC

Panelists: Aditya Bardia, MD, MPH, Massachusetts General Hospital Center; Claudine Isaacs, MD, Lombardi Comprehensive Cancer Center; Joyce OShaughnessy, MD, Baylor University Medical Center Texas Oncology; Tiffany Traina, MD, Memorial Sloan Kettering Cancer Center
Published: Wednesday, Mar 14, 2018



Transcript: 

Joyce A. O’Shaughnessy, MD: What about the anthracycline question, is that kind of a given in triple-negative breast cancer? Because we had a couple of studies like the PlanB trial and also the MINDACT trial. With the MINDACT, it was docetaxel/capecitabine versus an anthracycline regimen. In the PlanB, it was docetaxel/cyclophosphamide versus an anthracycline regimen. And they both showed no difference, but then the ABC trial showed a difference there, right?

Aditya Bardia, MD, MPH: And that was a larger trial in PlanB. ER-positive tumors were also included. In general, I think the standard of care this time is ACT. We’ve tried various different regimens. We’ve added Xeloda to neoadjuvant setting. We’ve added multiple other agents, but I think the standard at this time, at least in triple-negative breast cancer, is ACT. And I think we should be using it in a dose-dense fashion. We had a recent update at San Antonio, which looked at every 2 weeks versus 3 weeks, that demonstrated that every 2 weeks is better. This was based on the CALGB trial in United States also. So, I think every 2 weeks dose-dense chemotherapy for AC should be utilized. The taxane in triple-negative, I personally tend to use the weekly taxane given that it’s better than every 3 weeks, although sometimes you could also use every 2 weeks. But personally, I tend to use weekly paclitaxel and platinum as we discussed. But I think that is the standard, and if someone has residual disease, then it’s an open question as to what to do next.

Joyce A. O’Shaughnessy, MD: What was that update at San Antonio with regard to the Oxford and either sequential or dose dense?

Tiffany Traina, MD: So, to Aditya’s point, that update was the Early Breast Cancer Trialist Group, so we’re talking about dozens of thousands of women and many, many years of follow-up in terms of power there over some of the smaller ABC studies in PlanB. There are really a wealth of data in this last 5-year update. And there was a consistent about 15% increase in terms of the relative risk in incorporating an anthracycline, improving recurrence rates, improving disease-free survival, and improving OS with the incorporation of the anthracycline. And dose-dense Q2 was favored over Q3. We already know from the CALGB study that whether you gave your anthracycline and Cytoxan concurrently or split this up and sequentially gave ACT, the benefits were there. It’s really a matter of your dosing schedule that mattered, Q2 being superior to Q3.

Joyce A. O’Shaughnessy, MD: And the Oxford showed that, too, that there was no difference between the sequential and the concurrent. I thought that there was a little benefit there for sequential over concurrent, but that was not the case in the Oxford overview.

Tiffany Traina, MD: Yes, it’s more driven by that dose density.

Claudine Isaacs, MD: And if we put that into numbers, because we always talk about relative risk, in the Oxford overview, there was about a 4% to 5% absolute benefit for the dose-dense schedules and 3% to 4% for distant disease-free survival. So, these are substantial changes. I think the CALGB—even though for those of us who are old enough who remember doing that trial, and we were worried about the possibility of giving it dose dense and how it would be tolerated—we recognize that patients tolerate it extremely well and it’s actually a whole more convenient because they’re done with it quicker. So, now when you couple the tolerability and the clear benefit, I really think that there’s very solid and strong evidence that we should be giving things dose dense.

Joyce A. O’Shaughnessy, MD: That certainly would be sensible with AC. We don’t give it every 3 weeks now, and we certainly would give paclitaxel either dose dense or weekly, not every 3.

Tiffany Traina, MD: Correct.

Joyce A. O’Shaughnessy, MD: TAC regimen every 3 weeks? TAC?

Claudine Isaacs, MD: I can recall there was a trial looking at Taxotere using it dose dense, and it was really a hard drug and it wasn’t tolerable. So, I don’t think the data apply to regimens that include docetaxel.

Tiffany Traina, MD: Agreed. I think it’s much more challenging. And, interestingly, in the ECOG trial that Joe Sparano had published in comparing all the different taxane dosing and scheduling in the adjuvant setting, there you had weekly docetaxel versus Q3 and it was actually the Q3 docetaxel that appeared to be a smidgeon better than the weekly. So, I think it’s both by toxicity and benefit. It’s just harder to get into.

Joyce A. O’Shaughnessy, MD: But the Oxford, it wouldn’t probably be wrong to use TAC in standard practice. It’s on the NCCN still. I think it probably isn’t used as much as it used to be because of the toxicities concerned. There’s a low death rate from typhlitis with TAC, we know that. But it was not used that, that much. But I personally wouldn’t. I don’t think the Oxford overview specifically addressed triplet therapy versus a dose-dense approach. And, certainly, Sandy Swain had looked at TAC versus dose dense ACT, and there was no difference. That’s right, plus/minus gemcitabine, and that was actually the same. That was the same, so we do have data there. We do have that level 1 evidence that it would still be reasonable to do.

Tiffany Traina, MD: Although to your point there, as we’ve talked a bit about the art of medicine, when we’re using AC and then taxane and responding to how the patient is doing and the tumor is shrinking, we keep the door open to being able to add in a platinum. And if you’re already doing triplet concurrent therapy with TAC, I don’t know how you would then do that.

Joyce A. O’Shaughnessy, MD: Right. We wouldn’t have any data on that to help guide us.

Transcript Edited for Clarity 

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Transcript: 

Joyce A. O’Shaughnessy, MD: What about the anthracycline question, is that kind of a given in triple-negative breast cancer? Because we had a couple of studies like the PlanB trial and also the MINDACT trial. With the MINDACT, it was docetaxel/capecitabine versus an anthracycline regimen. In the PlanB, it was docetaxel/cyclophosphamide versus an anthracycline regimen. And they both showed no difference, but then the ABC trial showed a difference there, right?

Aditya Bardia, MD, MPH: And that was a larger trial in PlanB. ER-positive tumors were also included. In general, I think the standard of care this time is ACT. We’ve tried various different regimens. We’ve added Xeloda to neoadjuvant setting. We’ve added multiple other agents, but I think the standard at this time, at least in triple-negative breast cancer, is ACT. And I think we should be using it in a dose-dense fashion. We had a recent update at San Antonio, which looked at every 2 weeks versus 3 weeks, that demonstrated that every 2 weeks is better. This was based on the CALGB trial in United States also. So, I think every 2 weeks dose-dense chemotherapy for AC should be utilized. The taxane in triple-negative, I personally tend to use the weekly taxane given that it’s better than every 3 weeks, although sometimes you could also use every 2 weeks. But personally, I tend to use weekly paclitaxel and platinum as we discussed. But I think that is the standard, and if someone has residual disease, then it’s an open question as to what to do next.

Joyce A. O’Shaughnessy, MD: What was that update at San Antonio with regard to the Oxford and either sequential or dose dense?

Tiffany Traina, MD: So, to Aditya’s point, that update was the Early Breast Cancer Trialist Group, so we’re talking about dozens of thousands of women and many, many years of follow-up in terms of power there over some of the smaller ABC studies in PlanB. There are really a wealth of data in this last 5-year update. And there was a consistent about 15% increase in terms of the relative risk in incorporating an anthracycline, improving recurrence rates, improving disease-free survival, and improving OS with the incorporation of the anthracycline. And dose-dense Q2 was favored over Q3. We already know from the CALGB study that whether you gave your anthracycline and Cytoxan concurrently or split this up and sequentially gave ACT, the benefits were there. It’s really a matter of your dosing schedule that mattered, Q2 being superior to Q3.

Joyce A. O’Shaughnessy, MD: And the Oxford showed that, too, that there was no difference between the sequential and the concurrent. I thought that there was a little benefit there for sequential over concurrent, but that was not the case in the Oxford overview.

Tiffany Traina, MD: Yes, it’s more driven by that dose density.

Claudine Isaacs, MD: And if we put that into numbers, because we always talk about relative risk, in the Oxford overview, there was about a 4% to 5% absolute benefit for the dose-dense schedules and 3% to 4% for distant disease-free survival. So, these are substantial changes. I think the CALGB—even though for those of us who are old enough who remember doing that trial, and we were worried about the possibility of giving it dose dense and how it would be tolerated—we recognize that patients tolerate it extremely well and it’s actually a whole more convenient because they’re done with it quicker. So, now when you couple the tolerability and the clear benefit, I really think that there’s very solid and strong evidence that we should be giving things dose dense.

Joyce A. O’Shaughnessy, MD: That certainly would be sensible with AC. We don’t give it every 3 weeks now, and we certainly would give paclitaxel either dose dense or weekly, not every 3.

Tiffany Traina, MD: Correct.

Joyce A. O’Shaughnessy, MD: TAC regimen every 3 weeks? TAC?

Claudine Isaacs, MD: I can recall there was a trial looking at Taxotere using it dose dense, and it was really a hard drug and it wasn’t tolerable. So, I don’t think the data apply to regimens that include docetaxel.

Tiffany Traina, MD: Agreed. I think it’s much more challenging. And, interestingly, in the ECOG trial that Joe Sparano had published in comparing all the different taxane dosing and scheduling in the adjuvant setting, there you had weekly docetaxel versus Q3 and it was actually the Q3 docetaxel that appeared to be a smidgeon better than the weekly. So, I think it’s both by toxicity and benefit. It’s just harder to get into.

Joyce A. O’Shaughnessy, MD: But the Oxford, it wouldn’t probably be wrong to use TAC in standard practice. It’s on the NCCN still. I think it probably isn’t used as much as it used to be because of the toxicities concerned. There’s a low death rate from typhlitis with TAC, we know that. But it was not used that, that much. But I personally wouldn’t. I don’t think the Oxford overview specifically addressed triplet therapy versus a dose-dense approach. And, certainly, Sandy Swain had looked at TAC versus dose dense ACT, and there was no difference. That’s right, plus/minus gemcitabine, and that was actually the same. That was the same, so we do have data there. We do have that level 1 evidence that it would still be reasonable to do.

Tiffany Traina, MD: Although to your point there, as we’ve talked a bit about the art of medicine, when we’re using AC and then taxane and responding to how the patient is doing and the tumor is shrinking, we keep the door open to being able to add in a platinum. And if you’re already doing triplet concurrent therapy with TAC, I don’t know how you would then do that.

Joyce A. O’Shaughnessy, MD: Right. We wouldn’t have any data on that to help guide us.

Transcript Edited for Clarity 
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