Triple Negative Breast Cancer Treatment Update: Capecitabine, Immunotherapy and Platinum Salts

Drs Farzanna Haffizulla & Hope Rugo discuss triple-negative breast cancer treatments
Video originally published on PracticeUpdate on 3/27/2017: www.practiceupdate.com/c/4743...
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Dr Haffizulla: Now, focusing our discussion on TNBC what are your thoughts on adding adjuvant capecitabine in patients with residual disease after neoadjuvant chemotherapy?
Dr Rugo: The CREATE-X trial really has brought this to the forefront. We’ve always been interested in what we can do, in particular for patients with triple-negative breast cancer who don’t have more treatment options after they finish neoadjuvant therapy and have surgery, if they residual disease. Patients who have no cancer left in the breast and lymph node do very well. Although it’s not universally that they will be cured of their cancer, the relapses are very uncommon. If you do develop metastatic disease with triple-negative breast cancer, you have a reasonably short median survival, so this is an area of great interest.
You know, for some patients who have aggressive ER-positive disease, that’s also an issue where the relapse rates can be high. There have been trials looking at this, none of which have been positive, but a trial looked specifically just at capecitabine in patients with residual disease after neoadjuvant therapy and was performed in Japan and Korea, called CREATE-X. They randomized patients to either not get capecitabine or to get capecitabine at a higher dose than usually people in the US tolerate certainly, and we know that the metabolism of the drug is different in some Asian patients than in non-Asian patients, so there may be that. But they gave 8 cycles of capecitabine and then stopped and they followed these patients for both disease-free and overall survival and showed that that not only did the women who took capecitabine have less relapses, but they also lived longer. It was very impressive data. Then they looked at subsets and found that patients with triple-negative breast cancer appeared to be the subset that were benefiting more than patients with ER-positive disease.
That was quite intriguing and, I think, we’ve really looked at that data, it’s not published yet, it’s been presented. People have looked at the data in a little bit more detail and looked at some other studies to try and see if we could take out bits and pieces and understand this better, but I think that given that we have no options, using capecitabine is a reasonable option for a patient who has significant residual disease. I'm not talking about somebody who has a millimeter or 2, but significant residual disease because their relapse risk in the next 2 years is so very high.
Dr H: Have you started incorporating this into your clinical practice?
Dr R: We do use capecitabine in patients who have a lot of residual disease now. It seems like there’s randomized trial data, albeit, not published. Don’t give it to everybody. I give it primarily to patients with triple-negative disease, not ER-positive.
Dr H: Are you routinely using platinum agents in patients with TNBC irrespective of BRCA status?
Dr R: Well, you know, there’s data showing improved pathologic complete responses, but in the US randomized trial which had 2 chemotherapy regimen most similar to what we all normally do, there was no difference in disease-free survival and it does cause decreased blood counts and a little more nausea. I don’t give carboplatin or cisplatin as a routine additive drug, but I do give it for patients who are, for ex., poor responders or not responders in the neoadjuvant setting during standard treatments. I'm very interested in an ongoing Cooperative Group trial which is randomizing women with residual disease to either receive the platinum of physician choice versus capecitabine. That’s, I think, an incredibly important trial. In a patient who’s already had prior chemotherapy, has a recurrence of triple-negative disease, but is still curable, I usually give a taxane plus a platinum.
Dr H: Is there any other new promising data that may give hope to patients with triple-negative disease?
Dr R: They’ve sort of been a beleaguered group, you know, without new data, but now we do have, we have CREATE-X for post neoadjuvant therapy, but I think most importantly it’s an era of immunotherapy. We’re looking at immune checkpoint inhibitors and we’re also looking at combinations of immune active drugs, so one drug that might sort of goose up the immune system and then you come in with a checkpoint inhibitor so that it can unleash the immune system on the cancer after it’s already been amplified. That’s worth going on and there’s a lot of excitement about that in triple-negative breast cancer. Of course in the BRCA patients, patients who have BRCA germline mutations, there are 2 PARP inhibitor trials that will complete accrual next year, and the OlympiAD trial, it’s already completed accrual, will hopefully report at ASCO, so we’ll see some data very soon.

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One concern that after all treatment such as surgery, chemo and radio therapy
In TNBC stage 2 b, Is there any other therapy or oral tablets
required such as hormonal, immuno or
targeted therapy required after full treatment.