Discussion
asthenia, nausea, neutropenia, leukopenia, toxicities, vomiting, infection, toxic deaths
NEUTROPENIA, LEUKOPENIA, ADVERSE EFFECTS, INFECTION, METASTATIC BREAST CANCER, APPENDIX
The results of the CHEOPS study did not reach statistical significance, but showed a modest potential benefit of combining hormone therapy and metronomic chemotherapy in metastatic breast cancer HR + /HER2− pre-treated with endocrine therapy (HR 0.73, 95% CI 0.50–1.06, log-rank The limiting factor in this study was the number of toxic deaths induced by oral vinorelbine dose and administration scheme. Indeed, adverse effects of metronomic chemotherapy are most often mild or non-existent and are generally represented by grade 1 toxicities: leukopenia, moderate neutropenia, nausea and vomiting, increased transaminases and asthenia. Serious grade 3–4 toxicities are rare [The toxic deaths observed here may be the result of poor management of oral oncology drugs at home, for example, by maintaining chemotherapy during periods of neutropenia, infection or hospitalization, despite protocol recommendations. Recommendations for close biological monitoring have been strengthened accordingly (Appendix Table Other combinations may then be possible such as capecitabine and endocrine therapy or oral cyclophosphamide and endocrine therapy. Some studies evaluating combinations were carried out in the 1980s. These randomized trials compared chemotherapy most often with CMF (cyclophosphamide, methotrexate and 5 fluorouracil) as monotherapy with the same chemotherapy in combination with tamoxifen. These different studies showed significant benefit in terms of neoplastic response rate (74% versus 51%, respectively; P < 0.01; 75% versus 49% p = 0.0001) and progression-free survival. However, there was no significant difference in terms of overall survival (111 weeks versus 78 weeks The underlying question is then the interest of maintaining endocrine therapy throughout the treatment, including successive chemotherapy lines. To finish, maintenance endocrine therapy (MET) after chemotherapy could be another way to combine endocrine therapy and chemotherapy. Sutherland et al. discussed four trials addressing the question of whether there is a benefit from introducing endocrine therapy following chemotherapy for metastatic breast cancer [Concerning prior treatment, only a minority of patients had previously received anti-CDK4/6 therapy. This treatment is now the gold standard for first-line treatment of HR + metastatic breast cancer. The results of the CHEOPS trial are therefore not applicable to current daily practice. However, these results do provide a proof of concept on a trend toward an improvement of outcomes with a combination of endocrine therapy and chemotherapy compared to chemotherapy alone. This concept should persist after exposure to anti-CDK4/6.