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ONCAlert | Upfront Therapy for mRCC

Neoadjuvant Studies Identifying Optimal Strategies for TNBC

Lauren M. Green
Published Online: 10:36 PM, Fri July 22, 2016
She cautioned, however, that this is an observational study and there is no comparator arm and no randomization. Nevertheless, “this regimen did behave in the way that other regimens behave in the neoadjuvant setting … and certainly this data is quite compelling.” She said that while anthracyclines remain the standard of care, researchers are anxiously awaiting results from an ongoing randomized phase II neoadjuvant study comparing the CbD regimen to carboplatin/paclitaxel (NCT02413320).
To address the issue of optimal taxane dosing, DeMichele noted results from the ETNA trial were also reported at ASCO this year.5 In this neoadjuvant trial, weekly paclitaxel dosed at 90 mg/m2 was compared with weekly 125 mg/m2 nab-paclitaxel (nab-P). Both regimens were administered for 3 weeks with 1 week of rest over 4 cycles and followed by 4 cycles of an anthracycline regimen selected by the investigator. In the paclitaxel arm, 110 of 349 patients had triple-negative disease, and this was true for 109 of 346 patients in the nab-P cohort.
There was an improvement in pCR rate with nab-P overall but it did not reach the 10% threshold set for difference in pCR rates. In the subgroup analysis of TNBC patients, no statistically significant benefit was seen with one taxane over the other, and nab-P was more toxic, with more grade 3 myelosuppression as well as fatigue and vomiting, said DeMichele.
“At this point, we don’t have enough evidence to convince us that nab-paclitaxel is superior, but I think we also do now have the benefit of knowing that it’s not inferior. For those patients who have allergic reactions to paclitaxel, nab-paclitaxel could be a very good alternative.”
Bevacizumab and Capecitabine
DeMichele noted that results are mixed, following numerous trials with bevacizumab. In an update of findings from the phase III ARTemis trial reported at ASCO this year, a very small pCR difference was seen between the control chemotherapy arm versus the group where bevacizumab was added, and in the TNBC subgroup, no difference was seen in disease-free or overall survival.
Despite a lack of defined benefit currently, DeMichele said, “Neoadjuvant therapy can give us a very nice way of starting to sort out biomarkers, and hopefully with these neoadjuvant trials, we can start to tease out, ‘is there a group of patients who will benefit with bevacizumab, because right now, we don’t know who they are.”
Additionally, neither adjuvant nor neoadjuvant data are compelling enough in her view to add capecitabine to these regimens for all patients. “However, I do think for patients who are at very high risk, with substantial residual disease after neoadjuvant therapy, it’s something I am considering.”
DeMichele is optimistic about the role of post-neoadjuvant trials as a way to improve treatment decision making. “This is a great model, because what it allows us to do is to give additional therapy to patients who aren’t responding to standard therapy. Rather than continuing to add more and more therapy to every patient—many of whom don’t need it—we can really focus on those patients who aren’t getting the benefit from our standard therapies and give them something else.
“This trial model allows us to answer that type of question with many fewer patients than would be required in a large adjuvant setting. I think you’re going to see more and more of these kinds of trials.”
  1. Sikov WM, Berry DA, Perou CM, et al. Event-free and overall survival following neoadjuvant weekly paclitaxel and dose-dense AC +/- carboplatin and/or bevacizumab in triple-negative breast cancer: outcomes from CALGB 40603 (Alliance). Presented at: 2015 San Antonio Breast Cancer Symposium; San Antonio, TX; December 8-12, 2015. Abstract: S2-05.
  2. von Minckwitz G, Loibl S, Schneeweiss A, et al. Early survival analysis of the randomized phase II trial investigating the addition of carboplatin to neoadjuvant therapy for triple-negative and HER2-positive early breast cancer (GeparSixto). Presented at the 2015 San Antonio Breast Cancer Symposium; San Antonio, Texas, December 8-12, 2015. Abstract S2-04.
  3. Rugo H, Olopade OI, DeMichele A, et al. Adaptive randomization of veliparib-carboplatin treatment in breast cancer. N Engl J Med. 2016;375(1):23-34.
  4. Sharma P, Kimler BF, Ward C. Prognosis of triple negative breast cancer patients who attain pathological complete response with neoadjuvant carboplatin/docetaxel and do not receive adjuvant anthracycline chemotherapy. J Clin Oncol. 2016; 34 (suppl; abstr 1015).
  5. Gianni L, Mansutti M, Anton A, et al. ETNA (Evaluating Treatment with Neoadjuvant Abraxane) randomized phase III study comparing neoadjuvant nab-paclitaxel (nab-P) versus paclitaxel (P) both followed by anthracycline regimens in women with HER2-negative high-risk breast cancer: A MICHELANGO study. J Clin Oncol. 2016; 34 (suppl; abstr 502).

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