Log rank P =0.0 1 2 three four five 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 MonthMedian estimated all round survival time (80 CI): High rilotumumab exposure (n =41) 13.2 (10.6sirtuininhibitor4.3) Low rilotumumab exposure (n =40) 9.five (7.5sirtuininhibitor1.1) Placebo (n =39) 8.9 (5.7sirtuininhibitor0.6) Log rank P=0.BRITISH JOURNAL OF CANCERMET subgroup PFS MET adverse High exposure group 13 0.73 (0.30sirtuininhibitor.77) Rilotumumab exposure groupRilotumumab exposure-response evaluation in gastric cancerInteraction P valuenHR (95 CI)P value0.Low exposure group2.03 (0.75sirtuininhibitor.49)0.MET positiveHigh exposure group0.33 (0.15sirtuininhibitor.72)0.0.Low exposure group0.60 (0.30sirtuininhibitor.17)0.0.OS MET damaging High exposure group 13 1.19 (0.49sirtuininhibitor.88) 0.Low exposure group MET positive1.29 (0.50sirtuininhibitor.35)0.Higher exposure group0.32 (0.15sirtuininhibitor.70)0.0.Low exposure group0.64 (0.32sirtuininhibitor.29)0.0.194 Favors rilotumumab + ECX 0.1 1 Favors placebo + ECXFigure two. Forest plots for progression-free survival (PFS) and all round survival (OS) with respect to low and high rilotumumab exposure and constructive and adverse tumour MET expression. Low rilotumumab exposure was defined as Cminsso94 mg ml sirtuininhibitor1, and higher rilotumumab exposure was defined as CminssX94 mg ml sirtuininhibitor1. MET positivity was defined as X25 membranous staining of tumour cells at any intensity, and MET negativity was defined as o25 membranous staining. CI, self-confidence interval; ECX, epirubicin, cisplatin, and capecitabine; HR, hazard ratio.A1.0 0.9 0.8 0.7 0.six 0.five 0.four 0.3 0.two 0.1 0.0 0Median estimated progression-free survival time (80 CI): MET-positive + rilotumumab 15 mg kgsirtuininhibitor (n =16) 5.1 (3.9sirtuininhibitor.0) MET-positive + rilotumumab 7.five mg kgsirtuininhibitor (n =25) six.9 (5.6sirtuininhibitor.five) MET-positive + placebo (n =17) four.4 (2.9sirtuininhibitor.9) Log rank P = 0.B1.0 0.9 0.8 0.7 0.6 0.five 0.TGF beta 2/TGFB2, Mouse/Rat (HEK293) four 0.SHH, Human (C24II) 3 0.two 0.1 0.0 0 two 4Median estimated overall survival time (80 CI): MET-positive + rilotumumab 15 mg kgsirtuininhibitor (n =16) 9.7 (7.7sirtuininhibitor3.four) MET-positive + rilotumumab 7.5 mg kgsirtuininhibitor (n =25) 11.1 (9.2sirtuininhibitor2.0) MET-positive + placebo (n =17) five.7 (four.7, ten.two) Log rank P = 0.Survival probabilitySurvival probability10 12 14 16 18 20 22 24 Month8 ten 12 14 16 18 20 22 24 26 MonthMedian estimated all round survival time (80 CI): MET-negative + rilotumumab 15 mg kgsirtuininhibitor (n =13) 11.PMID:24275718 1 (6.9sirtuininhibitor3.three) MET-negative + rilotumumab 7.five mg kgsirtuininhibitor (n =9) 12.1 (9.2sirtuininhibitor3.2)C1.0 0.9 0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 0.0 0Median estimated progression-free survival time (80 CI): MET-negative + rilotumumab 15 mg kgsirtuininhibitor (n =13) five.three (two.8sirtuininhibitor.7) MET-negative + rilotumumab 7.5 mg kgsirtuininhibitor (n =9) 4.0 (three.0sirtuininhibitor.0) MET-negative + placebo (n =11) five.4 (4.1sirtuininhibitor.6) Log rank P = 0.D1.0 0.9 0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 0.0 0 2 4MET-negative + placebo (n =11) 11.5 (eight.5sirtuininhibitor9.five) Log rank P = 0.Survival probabilitySurvival probability10 12 14 16 18 20 22 24 Month8 ten 12 14 16 18 20 22 24 26 MonthFigure 3. Kaplan eier analysis of progression-free survival (PFS) and general survival (OS). PFS is shown in a and C. OS is shown in B and D. PFS and OS had been examined primarily based on rilotumumab dose in the MET-positive (A, B) and MET-negative subgroups (C, D). MET positivity was defined as X25 membra.
