SAN ANTONIO—Adding carboplatin and veliparib to standard neoadjuvant chemotherapy improves pathologic complete response (pCR) among women with triple-negative breast cancer (TNBC), according to the first set of efficacy results from the adaptively randomized multidrug I-SPY 2 clinical trial. The findings were presented at the 2013 San Antonio Breast Cancer Symposium.

“The results predict that the veliparib/carboplatin regimen is highly likely to be superior to the control (standard) regimen for triple-negative breast cancer in a phase 3 trial,” reported Hope Rugo, MD, professor of medicine and director of breast oncology and clinical trials education at the UCSF Helen Diller Family Comprehensive Cancer Center in San Francisco, CA.

“Adaptive randomization successfully identified a biomarker signature for veliparib plus carbo on the basis of a modest number of patients,” she added. “There is a suggestion that hormone receptor–positive, HER2-negative tumors benefit little from this regimen and inclusion of tumors in this subset would therefore dilute its effect in a subsequent trial.”

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A total of 71 study participants (38 women with TNBC and 33 with hormone receptor (HR)–positive and HER2-negative breast cancer) were enrolled and randomly assigned to receive veliparib plus carboplatin in combination with standard neoadjuvant paclitaxel; 44 patients with HER2-negative breast cancer were concurrently randomly assigned to standard adjuvant chemotherapy.

pCR was defined as no residual tumor in breast or lymph nodes at the time of surgery. The estimated pCR rates for patients with TNBC are 26% for standard neoadjuvant therapy versus 52% for those administered veliparib, carboplatin, and standard paclitaxel, Dr. Rugo reported. For HER2-negative tumors, those numbers are 33% and 22%, respectively, she said.

Toxicity was “moderately elevated, as expected, but well-managed with dose reductions and delays,” Dr. Rugo said.

These findings also indicate that the innovative adaptive-randomization design of the I-SPY 2 multidrug trial “can generate results that will power phase 3 registration trials,” Dr. Rugo added. The adaptive randomization design of the trial uses a computer algorithm to detect which patients respond better to which therapies as a trial proceeds; patients are randomly assigned to standard neoadjuvant (presurgical) anthracycline- and paclitaxel-based chemotherapy, or neoadjuvant paclitaxel in combination with a novel agent, followed by anthracycline-based chemotherapy.

Then, as the trial progresses and data accumulates on how different tumor subtypes respond to distinct investigational agents, the adaptive trial design allows women to be “assigned with higher probability to therapies that are performing better for patients of their subtypes,” Dr. Rugo explained. “Each new patient benefits from information from the previous patient.”

“By identifying which patients benefit, we can reduce trial size, accelerate drug development, and avoid overtreatment in the majority of patients, which is the future of drug development,” she said.

Adaptive randomization “is a new way of getting new drugs to market rapidly,” agreed panel moderator Peter Ravdin, MD, PhD, clinical professor of oncology at the University of Texas Health Science Center in San Antonio, TX.

Analyses are now underway to define additional pCR-predictive biomarkers, Dr. Rugo said. Future studies will need to compare survival outcomes with pCR data prior to US Food and Drug Administration approval, she cautioned.


  1. Rugo HS et al. S5-02. Presented at: San Antonio Breast Cancer Symposium 2013. Dec. 10-14, 2013; San Antonio.