Bisphosphonate plus chemotherapy ups chance for complete pathologic response

SAN ANTONIO—The concept of bisphosphonates as anticancer agents took a leap forward this week thanks to results from the AZURE trial. Investigators from the UK reported that patients receiving zoledronic acid(Drug information on zoledronic acid) along with neoadjuvant chemotherapy experienced a doubling in complete pathological response.

"This is the first patient-related evidence that this class of drugs may have direct antitumor activity," said Robert Coleman, MD, of the University of Sheffield during an SABCS 2008 press conference (SABCS abstract 5101).

Interest in the antitumor effect of bisphosphonates is on the rise, based in large part on the improvement observed in disease-free survival for women receiving zoledronic acid along with endocrine therapy (ASCO 2008 abstract LBA-4).

The work by Dr. Coleman and colleagues was a component of the AZURE trial that enrolled 3,360 women with stage II or III breast cancer. They received zoledronic acid in addition to neoadjuvant therapy. A retrospective exploratory evaluation of patients who received zoledronic acid (4 mg IV) with chemotherapy found that complete pathologic responses nearly doubled to 10.9% compared with 5.8% with chemotherapy alone, after adjusting for confounders.

Residual invasive tumor size was reduced to 28 mm in the zoledronic acid arm from 42 mm in the chemotherapy-alone arm. The median number of positive lymph nodes was three in the chemotherapy arm and two in the zoledronic acid-plus-chemotherapy arm. Sixty-five percent of the women in the zoledronic acid arm required mastectomy (rather than breast-conserving surgery) compared with 78% in the chemotherapy alone arm.

Dr. Coleman said that these results add significantly to the data generated from the Austrian Breast and Colorectal Cancer Study Group. AZURE included patients treated with chemotherapy, not endocrine therapy, and, most important, the impact of the drug on breast tissue itself was observed.

"This is the first evidence in a human model of a direct effect of bisphosphonates within the cancer cell," he said.