Figure 3.

The combination of afatinib plus crizotinib (a MET inhibitor) was effective against the afatinib‐resistant cell line showing MET amplification. A, Cell growth inhibition assay revealed that the combination of afatinib plus crizotinib was highly effective against the Calu3‐ARS cells showing MET amplification. B, Western blot analysis showed that afatinib inhibited the expression of p‐HER2 and crizotinib inhibited the expression of p‐MET in both the parental Calu3 and Calu3‐ARS cells. C, Mice with Calu3‐ARS tumors were given vehicle, afatinib, crizotinib, or afatinib plus crizotinib. The tumor volumes were determined on the indicated days after the start of treatment. Data represent the mean ± SE (n = 8). *P < .05 vs vehicle control by the t test. D, Appearance of the Calu3‐ARS tumors after treatment at the time of sacrifice of the mice