Figure 5

Phosphoinositide 3-kinase inhibition combined with HER2 inhibition is more effective at inducing tumor regression than HER2 inhibition alone. (A) Mice were injected with BT474 cells, and, after tumor formation, mice were treated with trastuzumab (T), lapatinib (L) or BKM120 (B) in the combinations indicated. Tumor growth was measured twice weekly. The log₂ tumor volume data is shown over the 28-day treatment course (bars = SEM). (B) Kaplan-Meier plot showing the number of mice in each treatment group whose tumors regressed to below 100 mm³ in volume during treatment. The number of responses and the total number in each group are displayed above the curve. (C) After 28 days of treatment, mice whose tumors had regressed were followed for recurrence. Tumor volume for individual mice is plotted with the color according to the initial treatment group. Arrows indicate retreatment with T + L + B. (D) Mice were injected with HCC1954 cells (H1047R PIK3CA mutant), and, after tumor formation, mice were treated with trastuzumab (T), lapatinib (L) or BKM120 (B) alone or in the combinations indicated. Tumor growth was measured twice weekly. The log₂ tumor volume data are shown over the 28-day treatment course (bars = SEM). Control, T and L alone mice were killed at day 21 of treatment because of excessive tumor volume. (E) After 28 days of treatment, mice from the T + L + B group whose tumors had regressed were followed for recurrence. Tumor volumes for individual mice are plotted. Red indicates mice whose tumors regrew, and those retreated with T + L + B are indicated by the arrow.