June 7, 2011 — Zoledronic acid, combined with anastrozole or tamoxifen, led to improved disease-free survival rates in women with stage I or stage II breast cancer, according to a study published online June 4 in The Lancet Oncology. The results suggest that zoledronic acid could be an important addition to adjuvant endocrine therapy in premenopausal patients with early-stage breast cancer.
The report outlined an analysis of the Austrian Breast and Colorectal Cancer Study Group trial 12, which is a randomized controlled, open-label multicenter trial. It included 1803 premenopausal women diagnosed with endocrine-receptor-positive breast cancer (stage I or stage II). All patients received goserelin (3.6 mg every 28 days).
Separate groups compared the efficacy and safety of anastrozole (1 mg/day) or tamoxifen (20 mg/day), with or without zoledronic acid (4 mg every 6 months). Participants were followed up for 3 years. Patients were randomly assigned to the 4 groups in a 1:1:1:1 ratio across prognostic variables that included age, neoadjuvant chemotherapy, pathological tumor stage, lymph node involvement, type of surgery or locoregional therapy, complete axillary dissection, intraoperative radiation therapy, and geographical region.
Median follow-up time was 62 months (range, 0 - 114.4 months). At least 2 years after treatment completion, there were a total of 186 disease-free survival events reported (53 events in 450 patients receiving tamoxifen alone, 57 in 453 patients receiving anastrozole alone, 36 in 450 patients receiving tamoxifen plus zoledronic acid, and 40 in 450 patients receiving anastrozole plus zoledronic acid).
Zoledronic acid was associated with a reduction in the risk for disease-free survival events (hazard ratio [HR], 0.68; 95% confidence interval [CI], 0.51 - 0.91; P = .009).The differences were not statistically significant for the tamixofen (HR, 0.67; 95% CI, 0.44 - 1.03; P = .067) and anastrozole (HR, 0.68; 95% CI, 0.45 - 1.02; P = .061) groups when they were analyzed individually.
Zoledronic acid had no influence on death (30 deaths with zoledronic acid vs 43 deaths without; HR, 0.67; 95% CI, 0.41 - 1.07; P = .09). Disease-free survival was the same in patients taking tamoxifen alone compared with patients taking anastrozole alone (HR, 1.08; 95% CI, 0.81 - 1.44; P = .591). Overall survival was lower in patients receiving anastrozole compared with patients receiving tamoxifen (46 vs 27 deaths; HR, 1.75; 95% CI, 1.08 - 2.83; P = .02).
The treatment regimens had no associated reports of renal failure or osteonecrosis of the jaw. Of the participants, 601 patients reported bone pain (33%; 349 patients receiving zoledronic acid vs 252 patients not receiving zoledronic acid), 361 reported fatigue (20%; 192 vs 169), 280 reported headaches (16%; 147 vs 133), and 266 reported arthralgia (15%; 145 vs 121).
"Addition of zoledronic acid improved disease-free survival in the patients taking anastrozole or tamoxifen," conclude lead author, Michael Gnant, MD, from the Medical University of Vienna, Austria, and colleagues. "There was no difference in disease-free survival between patients receiving anastrozole and tamoxifen overall, but those on anastrozole alone had inferior overall survival. These data show persistent benefits with zoledronic acid and support its addition to adjuvant endocrine therapy in premenopausal patients with early-stage breast cancer."
The study provides some insight into which patients could most benefit from zoledronic acid, according to Joanne Mortimer, MD, director of the women's cancer program at City of Hope, Duarte, California. "[Zoledronic acid] clearly has some benefit in some populations of women. The next step is figuring out who that population is. This study suggests that women who have low estrogen levels are the ones that benefit most from the bone treatment," Dr. Mortimer told Medscape Medical News.
The study received support from Novartis (zoledronic acid) and AstraZeneca (anastrozole, tamoxifen goserelin). The study authors have consulted for Novartis, AstraZeneca, Genomic Health, and Pfizer, as well as received lecture fees, travel awards, research support, and other compensation from Novartis, AstraZeneca, Sanofi-Aventis, Roche, Amgen, Pfizer, GlaxoSmithKline, and Schering. Dr. Mortimer has served as a consultant to Novartis in the past.
Lancet Oncol. Published online June 4, 2011. Abstract
The report outlined an analysis of the Austrian Breast and Colorectal Cancer Study Group trial 12, which is a randomized controlled, open-label multicenter trial. It included 1803 premenopausal women diagnosed with endocrine-receptor-positive breast cancer (stage I or stage II). All patients received goserelin (3.6 mg every 28 days).
Separate groups compared the efficacy and safety of anastrozole (1 mg/day) or tamoxifen (20 mg/day), with or without zoledronic acid (4 mg every 6 months). Participants were followed up for 3 years. Patients were randomly assigned to the 4 groups in a 1:1:1:1 ratio across prognostic variables that included age, neoadjuvant chemotherapy, pathological tumor stage, lymph node involvement, type of surgery or locoregional therapy, complete axillary dissection, intraoperative radiation therapy, and geographical region.
Median follow-up time was 62 months (range, 0 - 114.4 months). At least 2 years after treatment completion, there were a total of 186 disease-free survival events reported (53 events in 450 patients receiving tamoxifen alone, 57 in 453 patients receiving anastrozole alone, 36 in 450 patients receiving tamoxifen plus zoledronic acid, and 40 in 450 patients receiving anastrozole plus zoledronic acid).
Zoledronic acid was associated with a reduction in the risk for disease-free survival events (hazard ratio [HR], 0.68; 95% confidence interval [CI], 0.51 - 0.91; P = .009).The differences were not statistically significant for the tamixofen (HR, 0.67; 95% CI, 0.44 - 1.03; P = .067) and anastrozole (HR, 0.68; 95% CI, 0.45 - 1.02; P = .061) groups when they were analyzed individually.
Zoledronic acid had no influence on death (30 deaths with zoledronic acid vs 43 deaths without; HR, 0.67; 95% CI, 0.41 - 1.07; P = .09). Disease-free survival was the same in patients taking tamoxifen alone compared with patients taking anastrozole alone (HR, 1.08; 95% CI, 0.81 - 1.44; P = .591). Overall survival was lower in patients receiving anastrozole compared with patients receiving tamoxifen (46 vs 27 deaths; HR, 1.75; 95% CI, 1.08 - 2.83; P = .02).
The treatment regimens had no associated reports of renal failure or osteonecrosis of the jaw. Of the participants, 601 patients reported bone pain (33%; 349 patients receiving zoledronic acid vs 252 patients not receiving zoledronic acid), 361 reported fatigue (20%; 192 vs 169), 280 reported headaches (16%; 147 vs 133), and 266 reported arthralgia (15%; 145 vs 121).
"Addition of zoledronic acid improved disease-free survival in the patients taking anastrozole or tamoxifen," conclude lead author, Michael Gnant, MD, from the Medical University of Vienna, Austria, and colleagues. "There was no difference in disease-free survival between patients receiving anastrozole and tamoxifen overall, but those on anastrozole alone had inferior overall survival. These data show persistent benefits with zoledronic acid and support its addition to adjuvant endocrine therapy in premenopausal patients with early-stage breast cancer."
The study provides some insight into which patients could most benefit from zoledronic acid, according to Joanne Mortimer, MD, director of the women's cancer program at City of Hope, Duarte, California. "[Zoledronic acid] clearly has some benefit in some populations of women. The next step is figuring out who that population is. This study suggests that women who have low estrogen levels are the ones that benefit most from the bone treatment," Dr. Mortimer told Medscape Medical News.
The study received support from Novartis (zoledronic acid) and AstraZeneca (anastrozole, tamoxifen goserelin). The study authors have consulted for Novartis, AstraZeneca, Genomic Health, and Pfizer, as well as received lecture fees, travel awards, research support, and other compensation from Novartis, AstraZeneca, Sanofi-Aventis, Roche, Amgen, Pfizer, GlaxoSmithKline, and Schering. Dr. Mortimer has served as a consultant to Novartis in the past.
Lancet Oncol. Published online June 4, 2011. Abstract
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