BEST ADJUVANT REGIMEN FOR BREAST CANCER

Hi. It's Dr. Kathy Miller from Indiana University. Today's Medscape blog was prompted by a question from an oncologist in Indianapolis about the current standard or best way to give anthracycline- and taxane-based regimens in the adjuvant setting to patients with HER2-negative but high-risk disease. I think his frustration was that our trials have asked many questions but haven't directly compared the regimens that he had been considering. So, here is my flow of thinking about this. I will tell you the regimen that I would choose for the majority of patients in this setting.

Let's start with the advent of dose-dense therapy. The Cancer and Leukemia Group B (CALGB) 9741 study,^[1] looking at accelerating both the anthracycline and taxane components every 2 weeks using growth factors, clearly found an improvement, but the Gruppo Oncologico Nord Ovest (GONO) 1 trial,^[2] looking at only anthracycline, didn't reach statistical significance and found modest improvement at best. That raised questions about how much of the CALGB trial results were purely based on changing the taxane schedule. Things got more confusing, and questions about the taxane schedule got even louder, when we saw the results of the Eastern Cooperative Oncology Group (ECOG) 1199 trial.^[3] In that trial, they gave anthracycline every 3 weeks and then compared docetaxel with paclitaxel given weekly or every 3 weeks. They found that either docetaxel every 3 weeks or paclitaxel weekly was superior in efficacy, but weekly paclitaxel had substantially less toxicity. ECOG 1199, which was designed before we had the dose-dense results and did not include paclitaxel given every 2 weeks, gave us a real struggle in how we should incorporate those data.

Some would have ignored all of this and looked entirely at combination regimens with the TAC regimen that is used in many of the National Surgical Adjuvant Breast and Bowel Project (NSABP) trials. We finally have one direct comparison of TAC with dose-dense AC followed by paclitaxel.^[4] There is no difference in efficacy. There is different toxicity and, at least in my mind, substantially less toxicity with dose-dense therapy and a 2-week, short treatment duration. But there are no major differences.

The last study to consider is the most recent SWOG study, the SO221 study,^[5] which looked at only the taxane component of the schedules and compared dose-dense therapy every 2 weeks with weekly paclitaxel. There was no difference in efficacy and substantially less toxicity with weekly.

If you look at the cross-trial comparisons, there is no compelling reason to make the anthracyclines dose-dense or every 2 weeks. I do see compelling reasons to use paclitaxel weekly.

So, what would my standard recommendation be? AC every 3 weeks followed by weekly paclitaxel. There is a side benefit to that choice as your standard therapy, a benefit for economics and the healthcare system. There is less use of growth factors, and no prophylactic use of growth factors is needed, but it is at the cost of greater time to deliver therapy. I still think that dose-dense therapy has a role, particularly for patients for whom the time it takes to complete therapy is important. But for the majority of patients, I would avoid growth factors, take a little bit more time, minimize toxicity, and minimize the cost.

I would love to hear your thoughts about how you would combine the results of all of these trials and what your preferred regimen would be.