SAN ANTONIO – When it comes to adjuvant bisphosphonate therapy following adjuvant chemotherapy for high-risk early breast cancer, more is not better than less, phase 3 data from the randomized study suggest.
Among 3,421 patients randomized to adjuvant bisphosphonate therapy following chemotherapy, there was barely a speck of difference in either disease-free survival (DFS) or overall survival (OS) between patients randomized to either 2 years or 5 years of adjuvant bisphosphonate therapy with zoledronate, reported, from University Hospital Ulm (Germany).
“We conclude 5 years of adjuvant zoledronate treatment should not be considered currently in these patients in the absence of decreased bone density,” he said at the San Antonio Breast Cancer Symposium.
Adjuvant bisphosphonate therapy in patients with early breast cancer is associated with improved breast cancer–specific survival and reduced rates of breast cancer recurrence in bone, especially for postmenopausal patients, as shown in afrom the Early Breast Cancer Trialists’ Collaborative Group, Dr. Janni noted.
German breast cancer guidelines state that postmenopausal women should be offered bisphosphonates as part of their adjuvant systemic therapy, but the optimal duration of therapy is uncertain, prompting the investigators to examine the issue in a randomized trial.
SUCCESS A was a multicenter, phase 3, randomized trial with a multifactorial 2 x 2 design, in patients with high-risk node-negative and node-positive disease. Patients were randomized to FEC100 chemotherapy followed by docetaxel with or without gemcitabine. Chemotherapy was followed by endocrine therapy with 2 years of tamoxifen followed by 3 years of anastrozole (Arimidex). At the start of endocrine therapy, patients were further randomized to receive either 2 or 5 years of adjuvant zoledronate, 4 mg intravenously every 3 months for 2 years, or the same schedule over 2 years, followed by 4 mg every 6 months for 3 years.
A total of 2,987 of the 3,421 patients randomized to a zoledronate schedule were available for inclusion in the analysis.
As noted, adapted DFS and OS, measured starting from 2 years after the start of zoledronate with a maximum observation time of 48 months, were virtually identical between the two treatment groups, with respective P values of .827 and .713. Similarly, in a multivariate regression analysis model adjusted for age, body mass index, menopausal status, tumor size, nodal stage, histological grade and type, hormone receptor status, HER2 status, surgery type, and chemotherapy regimen, the hazard ratio for 5 vs. 2 years was 0.97 for DFS and 0.98 for OS. Neither endpoint was significantly different between the groups.
Similarly, there was no significant differences in the number of bone recurrences as first distant recurrences or in premenopausal vs. postmenopausal women.
Adverse events of any grade were significantly higher with 5 years of bisphosphonate therapy (46.2% vs. 27.2%, P less than .001), including significantly higher grade 3 or greater adverse events (7.6% vs. 5.1%, P = .006).
Following presentation of the data in an oral session, moderator Sibylle Loibl, MD, PhD, of the German Breast Group in Neu-Isenburg, Germany, questioned whether the follow-up was long enough to detect a clinically meaningful difference.
“The negative result of this study might be due to the small observation time,” Dr. Janni conceded.”We have a quite intensive drug regimen for the first 2 years, so this might also be a contributing factor [as to why] we did not see any difference.”
The SUCCESS A study was supported by AstraZeneca, Chugai, Janssen Diagnostics, Lilly, Novartis, and Sanofi-Aventis. Dr. Janni has reported financial relationships with AstraZeneca, Chugai, Janssen, Lilly, Novartis, and Sanofi.
SOURCE: Janni et al. SABCS 2017 Abstract