Figure 6.

Ribociclib and paxalisib treatment of G3MB and SHHMB in vivo. A, Treatment schedule after enrollment. B–G, Mice bearing PDXs HD-MB03 (B and C) MB002 (D and E) or SJMBSHH-13–5634 (F and G) tumor cells treated with vehicle (black lines), ribociclib (100 mg/kg, continuous daily by oral gavage (OG), red lines), paxalisib (10 mg/kg, continuous daily OG, green lines), or the combined formulation (continuous daily OG, blue lines) until moribund. (B, D, F) Kaplan-Meier survival plots for all treatment groups. Comparison between treatment groups using log-rank test adjusted for multiple comparisons [not significant (n.s.), adjusted *, P ≤ 0.05, adjusted **, P ≤ 0.01, and adjusted ***, P ≤ 0.001]. Median survival for HD-MB03–bearing mice in days: Vehicle: 20; ribociclib: 25; paxalisib: 27; combination: 32; ribociclib versus vehicle: adjusted P = 0.0795; combination versus vehicle: adjusted P = 0.003; combination versus ribociclib: adjusted P = 0.3674. Median survival for MB002-bearing mice in days: Vehicle: 28.5; ribociclib: 42.5; paxalisib: 33.5; combination: 51.5; ribociclib versus vehicle: adjusted P = 0.0005; combination versus vehicle: adjusted P = 0.0005; combination versus ribociclib: adjusted P = 0.1456. Median survival for SJMBSHH-13–5634-bearing mice in days: vehicle: 48; ribociclib: 71.5; paxalisib: 46; combination: 73; ribociclib versus vehicle: Adjusted P = 0.0005; combination versus vehicle: Adjusted P = 0.0028; combination versus ribociclib: Adjusted P = 0.4886. Mice were imaged twice weekly by bioluminescence imaging (BLI). C, E, and G, BLI pictures at different time points from enrollment through moribund stage represented for one mouse per treatment group. Mice selected on the basis of tumor and spinal growth median behavior. For BLI signal curves see Supplementary Fig. S7.