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SABCS 2014: Adding Carboplatin to Neoadjuvant Therapy Increases Pathologic Complete Response Rates Across Subtypes in Triple-Negative Breast Cancer

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Key Points

  • Tumors from patients with triple-negative breast cancers in the CALGB/Alliance 40603 trial were analyzed by intrinsic subtype and assessed for the effect of carboplatin or bevacizumab added to neoadjuvant chemotherapy.
  • Carboplatin increased the rate of pathologic complete response in both basal-like and non–basal-like subtypes.
  • Bevacizumab increased pathologic complete response rates only in the basal-like subtype.

Among women with triple-negative breast cancer, both basal-like and non–basal-like tumors were equally likely to demonstrate a pathologic complete response to neoadjuvant chemotherapy, but they responded differently to exposure to carboplatin and bevacizumab (Avastin), in an analysis of the CALGB/Alliance 40603 study presented at the 2014 San Antonio Breast Cancer Symposium (Abstract S4-05).

“The magnitude of pathologic complete response benefit with carboplatin was consistent across subtypes, while a basal-like pattern was predictive of greater pathologic complete response increment with bevacizumab,” said William Sikov, MD, of Women and Infants Hospital and Alpert Medical School of Brown University, Providence, Rhode Island.

While carboplatin increased pathologic complete response rates equally for women with basal-like and non–basal-like tumors, the addition of bevacizumab contributed benefit only among women with basal-like tumors, and the drug actually diminished pathologic complete responses in women with non–basal-like cancers, he said.

CALGB 40603 Details

The randomized phase II trial included 443 patients with stage II to III triple-negative breast cancer who underwent neoadjuvant chemotherapy. The study evaluated the benefit of adding carboplatin (AUC 6) or bevacizumab (10 mg/kg) to a standard neoadjuvant regimen of paclitaxel plus doxorubicin and cyclophosphamide.

At the San Antonio meeting last year, Dr. Sikov and colleagues reported that either agent increased pathologic complete response rates. In this analysis, the investigators drilled deeper for a closer examination of 360 tumor samples by intrinsic subtype. They classified the tumors as basal-like (n = 313), which tends to carry a worse prognosis, or non-basal-like (n = 47). Non–basal-like tumors were a mix of subtypes, including HER2-enriched, normal-like, claudin-low, and luminal A.

The overall pathologic complete response rate in these subtyped samples did not differ between basal-like (54%) and non–basal-like (52%), but some treatment interactions were noted.

In patients in the basal-like cohort randomly assigned to carboplatin or no carboplatin, pathologic complete response in the breast was achieved by 61% of the carboplatin arm vs 47% in the standard chemotherapy arm. The findings were similar for non–basal-like tumors, where pathologic complete responses were achieved by 58% and 45%, respectively.  

In contrast, subtype was important for the achievement of pathologic complete response in the bevacizumab cohorts. In basal-like patients, pathologic complete response rates were 64% with bevaciziumab and 45% without, but for the other subtypes, the rates were 43% and 60%, respectively, indicating a trend toward worse responses when bevacizumab was added.

Bevacizumab benefit was significantly greater in the basal-like subtype, increasing the odds of achieving a pathologic complete response. 

The findings were similar for pathologic complete responses in the breast and axillae, he noted.

Clinical Implications

“While these are interesting observations, I don’t think our data will change clinical practice,” Dr. Sikov predicted. For one thing, interest in using bevacizumab, especially in early-stage triple-negative disease, has diminished following disappointing results from several phase III studies, he said.

Regarding the use of carboplatin in the neoadjuvant setting for triple-negative disease, he said, “The jury is still out.”

“I don’t think the results we presented today will change anyone’s mind,” Dr. Sikov indicated at a press briefing. Some clinicians will see a 14% overall increase in pathologic complete response with carboplatin as part of the regimen, will acknowledge that there is toxicity but deem it acceptable, and will appreciate that the platinum agent is available and inexpensive. “They may feel it’s worthwhile,” he said.  

Other clinicians may feel the absolute increase is not as high as they would like to see, will point to the lack of long-term outcomes, will see that toxicity is somewhat increased, and conclude that they will not use carboplatin at this time, Dr. Sikov said.

Funding for the study was provided by the National Cancer Institute, Roche-Genentech, and the Breast Cancer Research Foundation. Dr. Sikov reported no potential conflicts of interest.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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