Adjuvant denosumab in early breast-cancer.

Abstract

We read with great interest the results of the D-CARE trial reported by Robert Coleman and colleagues. 1 Coleman R Finkelstein DM Barrios C et al. Adjuvant denosumab in early breast cancer (D-CARE): an international, multicenter, randomised, controlled, phase 3 trial. Lancet Oncol. 2020; 21: 60-72 Summary Full Text Full Text PDF PubMed Scopus (57) Google Scholar In this randomised, placebo-controlled trial, the effect of denosumab in combination with adjuvant or neoadjuvant systemic therapy in women with high-risk early breast cancer was assessed. Results for the primary and secondary endpoints showed that there was no evidence that adjuvant denosumab improves disease-related outcomes in these patients. Results for safety showed that a higher proportion of patients in the denosumab group developed osteonecrosis of the jaw, atypical femur fracture, and hypocalcaemia than in the placebo group. Given these observations, it seems reasonable to conclude that the risk of harm for the dose and indication of denosumab studied in the D-CARE trial 1 Coleman R Finkelstein DM Barrios C et al. Adjuvant denosumab in early breast cancer (D-CARE): an international, multicenter, randomised, controlled, phase 3 trial. Lancet Oncol. 2020; 21: 60-72 Summary Full Text Full Text PDF PubMed Scopus (57) Google Scholar outweighed the expected benefits. The benefit-to-risk balance of denosumab is therefore negative in this setting. Adjuvant denosumab in early breast-cancerWe read with interest the D-CARE trial report by Robert Coleman and colleagues1 on the adjuvant administration of denosumab in patients with early-stage breast cancer. Despite the negative results, which pose concerns about high dose denosumab schedules in an adjuvant setting, this large and well-designed trial can provide useful clinical data that are usually difficult to obtain from observational studies, particularly regarding medication-related osteonecrosis of the jaw (MRONJ). In the D-CARE trial,1 Coleman and colleagues studied the incidence of osteonecrosis of the jaw in patients who received denosumab or placebo. Full-Text PDF Adjuvant denosumab in early breast cancer (D-CARE): an international, multicentre, randomised, controlled, phase 3 trialDespite preclinical evidence suggesting RANKL inhibition might delay bone metastasis or disease recurrence in patients with early-stage breast cancer, in this study, denosumab did not improve disease-related outcomes for women with high-risk early breast cancer. Full-Text PDF Adjuvant denosumab in early breast cancer – Authors' replyWe thank The Lancet Oncology for the opportunity to respond to the correspondence about the D-CARE trial report1 on adjuvant denosumab in early breast cancer. This trial1 failed to show any benefit from the addition of denosumab to standard local and systemic adjuvant treatments for stage II or III breast cancer. Full-Text PDF Adjuvant denosumab in early breast cancerWith interest, we read the report on the D-CARE trial by Robert Coleman and colleagues,1 published in The Lancet Oncology, showing the absence of benefit for adjuvant denosumab treatment on bone metastasis-free survival and disease recurrence in patients with early-stage breast cancer, regardless of menopausal status. These results contrast with the positive outcome of treatment in postmenopausal women in the AZURE trial2 of adjuvant zoledronic acid therapy and the ABCSG study,3 which treated patients with a lower dose of denosumab (60 mg) than in the D-CARE trial1 (120 mg). Full-Text PDF Adjuvant denosumab in early breast cancerThe development of new therapeutic protocols that are able to reduce or inhibit the formation of metastatic bone lesions is a major challenge. In The Lancet Oncology, Robert Coleman and colleagues1 report the results of D-CARE trial, in which they randomly assigned 4509 women with high-risk early breast cancer to receive treatment with either denosumab (a fully human monoclonal antibody that inhibits the receptor activator of RANKL) or placebo. Despite experimental investigations showing that the use of RANKL inhibitor molecules delayed the occurrence of skeletal-related events,2 in the D-CARE trial, the use of denosumab did not improve disease-related outcomes for women with high-risk early breast cancer. Full-Text PDF