Figure 5 from The Next-Generation Oral Selective Estrogen Receptor Degrader Camizestrant (AZD9833) Suppresses ER<sup>+</sup> Breast Cancer Growth and Overcomes Endocrine and CDK4/6 Inhibitor Resistance

Abstract

<p>Enhanced efficacy of camizestrant in combination with PI3K/AKT/mTOR inhibitors as doublets in CDK4/6-sensitive and -resistant models (<a href="#bib1" target="_blank">1</a>). <b>A–D,</b> Combination of camizestrant with PI3Kα inhibitor alpelisib (<b>A</b>), mTOR inhibitor everolimus (<b>B</b>), AKT inhibitor capivasertib (<b>C</b>), or CDK4/6 inhibitor palbociclib (<b>D</b>) delivers enhanced efficacy compared with monotherapy in D538G <i>ESR1</i>m PDX CTC-174. Statistical analysis was performed by one-tailed, unequal variance <i>t</i> test versus log (change in tumor volume) compared with vehicle control at the final day of treatment. <b>E,</b> Relative tumor volume plots of ST3632 PDX model treated with oral camizestrant at 10 mg/kg daily, oral palbociclib at 50 mg/kg daily, and oral abemaciclib 50 mg/kg daily, and with camizestrant + abemaciclib and camizestrant + palbociclib. Statistical analysis was performed by one-tailed, unequal variance <i>t</i> test versus log (change in tumor volume) at the final day of treatment. <b>F,</b><i>In vivo</i> combination of camizestrant at 10 mg/kg daily with palbociclib 50 mg/kg, abemaciclib 50 mg/kg, and capivasertib 130 mg/kg in PDX ST1799 dosed for 40 days (gray area). For clarity, the graph is divided into four subgraphs due to the large number of treatment arms; where they appear, the vehicle, camizestrant, and palbociclib arms are the same in each subgraph. CDK, cyclin-dependent kinase. *, <i>P</i> < 0.05; **, <i>P</i> < 0.01; ***, <i>P</i> < 0.001; ****, <i>P</i> < 0.0001; ns, not significant.</p>