4CPS-180 Assessment of capivasertib for treatment of advanced breast cancer

<h3>Background and Importance</h3> The European Medicines Agency (EMA) has recently granted approval for the use of capivasertib in the treatment of locally advanced or metastatic oestrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer with PIK3CA/AKT1/PTEN alterations that has progressed during or after endocrine therapy. <h3>Aim and Objectives</h3> To evaluate whether capivasertib and the main current standard treatments are equivalent therapeutic alternatives (ETA) by performing an indirect treatment comparison (ITC). <h3>Material and Methods</h3> In May 2024, a literature search was conducted in PubMed using the following criteria: treatment of HR+ HER2- breast cancer with capivasertib, alpelisib, or or cyclin-dependent kinase 4/6 inhibitors in combination with fulvestrant, in patients with PIK3CA alterations and progression on endocrine therapy. The comparison variable was progression-free survival (PFS). The Bucher method was used for the ITC. In order to establish therapeutic the optimal therapeutic positioning, the ETA guideline ¹ was applied. In accordance with the ESMO-MCBS criteria, the non-inferiority delta value (∆) was established as 0.65, and its inverse 1.54. The Shakespeare method was used to determine the probability of the result exceeding the equivalence ∆. <h3>Results</h3> The comparison included a phase III study on capivasertib, one on palbociclib, and one on abemaciclib. Alpelisib and ribociclib were not included in the analysis as they failed to meet the established criteria for comparison. The results of the clinical trials and the indirect comparison are presented below: The probability of a result falling outside the specified range for palbociclib was 35.7% above, 3.7% below, and 21.0% above for abemaciclib. <h3>Conclusion and Relevance</h3> In accordance with the ETA guideline, capivasertib cannot be considered ETAs in comparison to palbociclib and abemaciclib. There is no evidence indicating a superior efficacy of capivasertib in combination with fulvestrant compared to palbociclib and abemaciclib in combination with fulvestrant. Given the toxicity profile of capivasertib, the recommended initial treatment option for of CDK4/6 inhibitors remains unchanged. <h3>References and/or Acknowledgements</h3> Alegre Del Rey EJ, <i>et al</i>. Med Clin (Barc) 2014 −07–22;<b>143</b>(2):85–90. <h3>Conflict of Interest</h3> No conflict of interest