Fig. 4: Assessment of triple drug combinations using SynergyLMM.

a, b Heregulin + Fulvestrant + Trastuzumab triple drug combination effects on tumor growth in the MAS98.06 luminal-like breast cancer PDX model. The measurements for Control and Heregulin, Fulvestrant, and Trastuzumab single treatments correspond to the same data shown in Fig. 4b. Each curve corresponds to an individual mouse: control n = 5, Heregulin n = 5, Fulvestrant n = 5, Trastuzumab n = 5, Heregulin + Fulvestrant + Trastuzumab n = 5. c, d In vivo evaluation of Osimertinib + AZD2014 + Docetaxel triple drug combination effect on tumor growth in U87-MG FM orthotopic glioblastoma model. Each curve corresponds to an individual mouse: control n = 6, AZD2014 n = 7, Osimertinib n = 7, Docetaxel n = 7, AZD-2014 + Osimertinib + Docetaxel n = 7. a, c display tumor growth data for the different drug combinations across the distinct cancer models. The bold lines in the plots represent the fitted regression lines for the fixed effects of each treatment estimated by the linear mixed-effects models. The x-axis of the plot in c represents the original time in square-root scale. b, d show the synergy evaluation using SynergyLMM for MAS98.06 (b) and U87-MG FM (d) tumor models for Bliss, highest single agent (HSA), and response additivity (RA) synergy models. The horizontal dashed lines indicate the synergy score threshold of 0 to assess synergy or antagonism. The error bars indicate the 95% confidence intervals for the synergy score. The dot in the centers indicate the estimated synergy score value. The dot colors indicate the two-sided (non-adjusted) p value from SynergyLMM. Ctrl Control, Her Heregulin, Fulv Fulvestrant, Trast Trastuzumab, AZD AZD2014, Osi Osimertinib, Doc Docetaxel. Source data are provided as a Source data file.