Kathy D. Miller, MD; Hope Rugo, MD


December 20, 2013

In This Article

To Platinum or Not to Platinum?

Dr. Miller: To a US oncology audience, the same question -- to platinum or not to platinum? First the Bill Sikov study.[5]

Dr. Rugo: It is a good study to start with because it is a more standard design of a clinical trial. Bill Sikov had done some previous work in a randomized phase 2 trial that suggested high PCR rates with a regimen that includes carboplatin. A study was designed in the Cancer and Leukemia Group B (CALGB), which is now referred to as the Alliance (between 2 and 3 different cooperative groups), in which patients with tumors that were 2 cm or larger would be randomly assigned to receive carboplatin, bevacizumab, or the combination in a 2 x 2 randomized design, along with standard neoadjuvant chemotherapy that included weekly paclitaxel for 12 weeks, followed out back (and this is the same regimen that we use) with the standard anthracycline for 4 doses and then surgery.[5] The idea was that getting off chemotherapy before surgery was a good thing for patients with triple-negative disease. Anthracycline has some DNA-damaging effects, so it's good in combination, and if patients didn't get the anthracycline we wouldn't know how much additional benefit it provides after surgery. Patients were randomly assigned to receive bevacizumab or carboplatin in this 2 x 2 design so they could get both of them together. Investigators were able to analyze the individual contribution of bevacizumab and carboplatin with this design.

Dr. Miller: So, what works?

Dr. Rugo: Carboplatin. Bevacizumab works, but not as much.

Dr. Miller: The data are what they are.

Dr. Rugo: It works and it's very similar to what was seen in the previous GeparQuinto trial looking at bevacizumab in the neoadjuvant setting,[6] which is very interesting. If you separate out the effects of carboplatin, the difference is quite striking. The pCR in breast and axilla was 41% in the patients who got the standard chemotherapy and 54% with carboplatin. It's a big difference and the odds ratio is 1.7, so it is not dissimilar to what was seen in the GeparSixto trial.

Dr. Miller: It's remarkably similar.

Dr. Rugo: It is and it's quite intriguing. There is more toxicity if you add carboplatin but less than if you add bevacizumab, although the carboplatin toxicities are exactly what you would expect. There isn't a lot of thrombocytopenia but more bone marrow suppression and gastrointestinal side effects. Carboplatin was given as an area under the curve (AUC) of 6 every 3 weeks for 4 doses, not the AUC of 2 given continuously. If you look at different studies, maybe it is a little better tolerated than giving the AUC of 2 continuously (kind of counterintuitive, but probably the case), because in the Gepar study they gave it continuously.


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