Carboplatin Beneficial in Neoadjuvant Treatment of TNBC

AlishaCatherine

I came across this article last night and was wondering if any of you added it to your treatment. If so, did you have a good pathological response? Any more thought in this? 

"In the secondary endpoint of pCR rates by breast cancer subtype, among patients with TNBC there was what Dr. von Minckwitz called “a tremendous 20% absolute difference” in those receiving carboplatin (58.7%) compared with those not receiving carboplatin (37.9%)."

http://am.asco.org/addition-carboplatin-beneficial-neoadjuvant-treatment-triple-negative-breast-cancer

Adding carboplatin to a regimen of neoadjuvant therapy resulted in a significant increase in pathologic complete response (pCR) for patients with breast cancer, according to a presentation in the Breast Cancer—Triple-Negative/Cytotoxics/Local Therapy Oral Abstract Session, held June 3. An increase of more than 20% in pCR was seen in women with triple-negative breast cancer (TNBC), but no benefit was seen in those with HER2+ breast cancer in the study.

Gunter von Minckwitz, MD, of the German Breast Group, noted that there has been conflicting evidence regarding the efficacy of carboplatin in breast cancer. The GeparSixto trial (Abstract 1004) was a randomized phase II study comparing the results of neoadjuvant chemotherapy with and without the addition of carboplatin in 595 patients with centrally confirmed TNBC or HER2+ breast cancer.

Patients were randomly assigned to a weekly neoadjuvant chemotherapy regimen of paclitaxel and nonpegylated liposomal doxorubicin for 18 weeks, with or without carboplatin. Patients also received subtype-specific targeted therapy: trastuzumab and lapatinib in HER2+ disease and bevacizumab in TNBC.

The primary endpoint of the study was a comparison of pCR (ypT0 ypN0) rates between the two chemotherapy regimens. Secondary endpoints included compliance and toxicity, efficacy using other definitions of pCR, and efficacy in the HER2+ and TNBC subgroups.

Patients enrolled in the study had untreated unilateral or bilateral primary breast carcinoma, and TNBC or HER2+ status was confirmed by central pathology. Patient and tumor characteristics were well balanced between the treatment groups by age and by tumor size, stage, grade, and subtype. The percentages of patients with each tumor subtype were the same in each treatment group: 53.6% TNBC (315 patients) and 46.4% HER2+ (273 patients).

All six cycles of treatment were completed by 52.2% of the arm receiving carboplatin and 60.9% of the arm not receiving carboplatin. Discontinuation of all treatments because of an adverse event (AE) occurred in 37.7% and 31.5% of patients in those arms, respectively. Higher numbers of hematologic serious AEs (anemia, febrile neutropenia) were seen in the groups receiving carboplatin, and a higher number of gastrointestinal serious AEs in the group receiving carboplatin with trastuzumab.

For the primary endpoint of pCR there was a significant difference in pCR rate between the two arms at the level for which the study was powered (37.2% without carboplatin vs. 46.7% with carboplatin; p < 0.2, a = 0.2), Dr. von Minckwitz said. Differences between the arms were also seen when other definitions of pCR were applied.

In the secondary endpoint of pCR rates by breast cancer subtype, among patients with TNBC there was what Dr. von Minckwitz called “a tremendous 20% absolute difference” in those receiving carboplatin (58.7%) compared with those not receiving carboplatin (37.9%). The same was not true for patients with HER2+ disease; there was a slightly lower pCR rate for those receiving carboplatin (33.1%) than for those not receiving carboplatin (36.3%).

“Compared to our previous experience in other trials, these are very high rates of efficacy in both arms of the GeparSixto study,” Dr. von Minckwitz said. He observed, however, that the high rate of efficacy must be weighed against a high rate of treatment discontinuations in the study.

Discussant Judy E. Garber, MD, MPH, of the Dana-Farber Cancer Institute, commented on the high number of adverse events in the trial. “One wonders what modifications might have made this regimen more tolerable for women in all arms of the study,” she said. It remains to be determined in whom the platinum agents are effective, and whether and at what disease stage carboplatin can be added to the routine care of patients with TNBC.