Introduction

Although the introduction of CDK4/6 inhibitors in combination with standard endocrine therapy (ET) has improved progression free survival (PFS) and tumor response rates in metastatic hormone receptor positive/HER2-negative breast cancer (HR+/HER2- mBC2), most of the patients still progress and eventually die of their disease. Periodic cycles of water fasting/fasting mimicking diet (FMD) allow to further increase PFS and to induce tumor regressions in mouse models of HR+/HER2- BC when combined with ET and with a CDK4/6 inhibitor. In line with these findings from preliminary mouse models, promising results with this approach were obtained in patients enrolled in one clinical trial.

Technical features

The present invention relates to a therapeutic combination of ET and a CDK4/6 inhibitor with a reduced calorie intake for a period of 24-190 hours while patient is being treated with said therapeutic combination. The reduced calorie intake regimen preferably corresponds to less than 1,200 kcal/day, preferably 300-1,100 Kcal/day with foods with a high content of monounsaturated and polyunsaturated fats and a reduced content of proteins and sugars. The period of reduced calorie intake can be repeated one or more times after respective periods of 5-60 days, during which the patient is given ET and the CDK4/6 inhibitor while following a diet involving a normal calorie intake. The experimental results show that reduced calorie intake positively affects the anticancer efficacy of a concurrent treatment with endocrine therapy and a CDK4/6 inhibitor. The present invention is focused on the treatment of HR+/HER2- BC but it could also apply to all estrogen-responsive tumors.

Possible Applications

• Clinical trials;
• Clinical routine treatment of patients with HR+/HER2- BC.

Advantages

• Periods of reduced caloric intake can increase the efficiency of the therapeutic combination of ET with CDK4/6 inhibitors in HR+/Her2- breast cancer;
• The present invention could also apply to other estrogen responsive tumors.