Abstract 207P
Background
Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors, Phosphoinositide 3-kinase (PI3K)/mammalian target of rapamycin (mTOR) inhibitors and histone deacetylase (HDAC) inhibitors are used for restoring endocrine sensitivity inhormone receptor-positive (HR+), HER2- advanced breast cancer. The present study sought to compare the benefits of these agents as second-line treatment by conducting a comprehensive systematic review and network meta-analysis.
Methods
Medline, Embase and Cochrane Library were searched for randomized trials comparing CDK4/6 inhibitors, PI3K/mTOR inhibitors, or HDAC inhibitors vs. placebo added with Exemestane or Fulvestrant as second-line treatment until December 12, 2021. Progression-free survival (PFS), overall response rate (ORR) was compared.Rankings of different regimens were expressed as SUCRA values.
Results
After screening 450 citations, 17 studies were included in the current study, with a total of 7,439 participants. The rankings of different regimens were evaluated by SUCRA values. In terms of PFS, mTOR inhibitor plus exemestane was the best (SUCRA value 89.5%), CDK4/6 inhibitor plus fulvestrant was the second best one (77.8%), followed by mTOR inhibitor plus fulvestrant (77.6%), HDAC inhibitor plus exemestane (53.8%), and PI3K inhibitor plus fulvestrant (49.4%). Regarding ORR, mTOR inhibitor plus exemestane was also the best regimen (91.3%), CDK4/6 inhibitor plus fulvestrant was the second best (80.2%), and then PI3K inhibitor plus fulvestrant (69.5%), mTOR inhibitor plus fulvestrant (57.2%), and HDAC inhibitor plus exemestane (37.3%). The risks of severe adverse eventswere similar among all the treatments regimens, except for that mTOR inhibitor plus exemestane induced more SAE than HDAC inhibitor plus exemestane [OR, 95%CI: 2.40 (1.40-4.10)].
Conclusions
mTOR inhibitor and CDK4/6 inhibitors demonstrated superior efficacy compared to PI3K inhibitors and HDAC inhibitors with comparable safety profiles as second-line treatment in HR+, HER2- advanced breast cancer.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Ying Fan.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.