First-line treatment for endocrine sensitive bone-only metastatic breast cancer: a systematic review and meta-analysis

In the last decade, several clinical trials have investigated novel endocrine combinations for the first-line treatment of hormone receptor positive metastatic breast cancer. Nevertheless, the use of combinations for the first-line treatment of bone-only disease is widely discussed, due to its indolent natural history.

We performed a comprehensive search of phase III randomized clinical trials published in the literature through September 2018. Our aim was to explore the role of the new endocrine approaches in bone-only metastatic breast cancer, suggesting a possible strategy for their selection. In particular, we evaluated the comparative risk of adverse event occurrence during these treatments.

A total of 6 studies were deemed suitable for the meta-analysis: the Monaleesa-2, Monaleesa-7, Monarch-3, Paloma-2, SWOG and the Alliance trials. Overall, the novel strategies were shown to improve progression free survival in bone-only disease [HR 0.65, 95%CI 0.49-0.86, p 0.003]. Combinations with CDKi improve PFS [HR 0.54, 95%CI 0.39-0.75, p <0.001] with acceptable toxicity profile. Abemaciclib is associated with increased anemia and gastro-intestinal toxicity (especially diarrhea), while palbociclib is associated with increased leucopenia (but not neutropenia) compared to the other compounds. Increased AST were reported for both ribociclib and abemaciclib.

The combination of cyclin-dependent kinase 4/6 inhibitors and endocrine therapy represents an effective and well-tolerated approach for first-line treatment in bone-only disease settings as well. Since no direct comparison between the three cyclin-dependent kinase 4/6 inhibitors is available, the selection of the most appropriate treatment should be based on toxicity profile and patient preferences and co-pathologies.