Figure 4. Rapamycin prolongs PFS and OS after treatment with an irreversible EGFR TKI.
(A) Schema of switch maintenance therapy. See also Table S2.
(B) WZ4002 inhibits EGFR and the downstream Akt/mTOR pathway in mEGFRL+T-driven lung tumors. As a biomarker study, 6 lung tumor-bearing C/L858R+T790M mice on Dox for 7 weeks were given 2 doses of vehicle or WZ4002 (25 mg/kg once a day) by gavage. Lung tumors were extracted 3 hours after last administration. IB was performed using the indicated antibodies. (Note- the 2 doses administration of WZ4002 did not induce tumor regression (data not shown)).
(C) Two representative mice from the switch maintenance study. Mouse No. 8699 in vehicle group showed PD by day 14; on the other hand, rapamycin prevented disease progression to day 55 in mouse No. 6009. H, heart. L, left side. Red arrows indicate dense areas of lung tumors. See also Table S2.
(D) Rapamycin prolongs PFS. PD of mice in vehicle or rapamycin groups was assessed by criteria to classify tumor responses as described in Supplemental Experimental Procedures. Median PFS in vehicle and rapamycin group was 13.0 days and 17.5 days, respectively. HR, hazard ratio. See also Table S2.
(E) Rapamycin prolongs OS. Median OS in vehicle and rapamycin group was 37 days and 68 days, respectively. HR, hazard ratio. See also Table S2.