Efficacy and safety of abemaciclib plus endocrine therapy versus endocrine therapy alone in HR + and HER2-negative breast cancer; a systematic review and meta-analysis.

PURPOSE: Breast cancer is the most commonly diagnosed cancer worldwide. To evaluate the safety and efficacy of abemaciclib in combination with endocrine therapy (ET) for the treatment of Hormone Receptor/ Human Epidermal Growth Factor Receptor 2 (HR + /HER2-) advanced or metastatic breast cancer, this systematic review and meta-analysis compared several treatment regimens and patient groups.

METHODS

In this systematic review and meta-analysis, we searched (PubMed, Scopus, and the Cochrane from inception to 5 April 2025) to identify the studies that compared abemaciclib plus ET to ET alone. The measure effects used were hazard ratios (HR) for overall survival (OS), progression-free survival (PFS), and invasive disease-free survival (IDFS), while risk ratios (RR) for objective response rate (ORR), clinical benefit rate (CBR), and adverse effects· Forest plots were created using a random effects model, with a p-value < 0·05 was considered statistically significant. This study is registered on PROSPERO (CRD420251009464).

RESULTS

We included fourteen studies comprising 16,116 patients (8592 with abemaciclib plus ET and 7524 with ET alone), abemaciclib plus ET significantly improved PFS (HR 0·54; 95% CI 0·49-0·59, p = 0·00001), IDFS (HR 0·68; 95% CI 0·59-0·78, p = 0·00001), ORR (RR 2·87; 95% CI 1·85-4·44, p = 0·0001), and CBR (RR 1·32; 95% CI 1·14-1·52, p = 0·0002), and a non-statistically significant OS (HR of 0·86; 95% CI 0·74-1·01, p = 0·06). Abemaciclib increased the risk of adverse events; cardiovascular events (4·82 times), increased blood creatinine (8·51 times), nausea (1·95 times), vomiting (2·51 times), abdominal pain (2·64 times), decreased appetite (2·59 times), diarrhea (4·20 times), aspartate aminotransferase (AST) (2·15 times), alanine aminotransferase (ALT) (2·28 times), anemia (3·79 times), thrombocytopenia (5·73 times), leukopenia (5·48 times), neutropenia (8·74 times)· However, it showed a reduced risk of arthralgia (0·73 times).

CONCLUSION

The combination therapy provides a clinically significant improvement in survival and treatment responses, even though the toxicity is increased but manageable, and requires careful prescription.