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

Enhanced efficacy of camizestrant in combination with PI3K/AKT/mTOR inhibitors as doublets in CDK4/6-sensitive and -resistant models (1). A–D, Combination of camizestrant with PI3Kα inhibitor alpelisib (A), mTOR inhibitor everolimus (B), AKT inhibitor capivasertib (C), or CDK4/6 inhibitor palbociclib (D) delivers enhanced efficacy compared with monotherapy in D538G ESR1m PDX CTC-174. Statistical analysis was performed by one-tailed, unequal variance t test versus log (change in tumor volume) compared with vehicle control at the final day of treatment. E, 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 t test versus log (change in tumor volume) at the final day of treatment. F,In vivo 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. *, P < 0.05; **, P < 0.01; ***, P < 0.001; ****, P < 0.0001; ns, not significant.