ABCSG 18: Monoclonal antibody increases disease-free survival in breast cancer

Today, lead investigator Michael Gnant presented the results of the placebo-controlled, adjuvant study ABCSG 18, involving 3,425 postmenopausal breast cancer patients, to thousands of breast cancer experts in the general session of one of the largest and most important international symposia on breast cancer, the San Antonio Breast Cancer Symposium in San Antonio/Texas (8 -12 December 2015). The results indicate a further important benefit of treatment with the monoclonal antibody denosumab, which was administered as an adjuvant therapy to aromatase inhibitors within the framework of the ABCSG 18 study. The results of the primary study endpoint -- the effect of denosumab on bone health -- were published in "The Lancet" at the beginning of June 2015 and showed that drug-related osteoporosis and bone fractures can be reduced by a remarkable 50% as a side-effect of the adjuvant therapy, without any additional toxicity.

50% fewer bone fractures, 18% fewer relapses

The data have now been determined for an additional study endpoint, the impact of denosumab on disease-free survival (DFS). A total of 370 DFS events were recorded during the four-year period, 203 of these in the placebo group and 167 in the denosumab arm. This reduction in the recurrence rate of breast cancer is barely at the statistical significance threshold (HR=0.816, p=0.051).

"This result is very pleasing, because it shows that adjuvant denosumab not only halves the number of bone fractures but also reduces the rate of recurrence of breast cancer," says Gnant in his assessment of the results. "We have long dreamed of being able to positively influence the recovery rate by changing the micro-environment and we have succeeded once again with ABCSG 18," he adds.

Clear reduction in recurrences in certain subgroups

Explorative subgroup analyses indicate that some patients in particular benefit from the practically side-effect-free administration of denosumab in addition to the standard aromatase inhibitor treatment: There is a clearly significant result, especially in the case of tumours of more than 2 cm in size and early start of treatment and in tumours with a particularly high receptor density.

Gnant is now expecting that there will be changes in clinical practice before too long: "This means that denosumab, which hardly has any side-effects, is generally superior to bisphosphonates as an adjuvant therapy and, in my opinion, should be offered to all postmenopausal, hormone-receptor-positive breast cancer patients." We know that bisphosphonates, which are used for treating osteoporosis, can have a positive impact upon disease-free survival. Denosumab acts in a similar way to bisphosphonates but is more effective and less toxic and can easily be given as a subcutaneous injection (60 mg subcutaneously 2x year).