vs T 790 M EGFRM T 790 EGFR

奥希替尼vs埃克替尼 药物名称 奥希替尼 埃克替尼-一代 艾维替尼-三代 机理 T 790 M抑制剂（一线 和二线） EGFRM+（一线） T 790抑制剂（一线 和二线） EGFR一线无进展期 (PFS，月) 19. 3 11. 6 ORR 80 %（76%）（QD） 71 41. 7% （BID） 艾维替尼： 2016年ESCO年会公布的临床I/II期（NCT 02274337）研究数据中， 结果显示ORR和DCR分别为 41. 7％和75. 0％。在≥ 350 mg，两次服药。 https: //mp. weixin. qq. com/s/2 IKx 8 f. Kb. F 30 etnb. CBm. Bm 2 w 奥希替尼：At data cutoff (November 1, 2016), median follow-up was 19. 1 months. Overall ORR was 67% (95% CI, 47% to 83%) in the 80 -mg group, 87% (95% CI, 69% to 96%) in the 160 -mg group, and 77% (95% CI, 64% to 87%) across doses. Median PFS time was 22. 1 months (95% CI, 13. 7 to 30. 2 months) in the 80 -mg group, 19. 3 months (95% CI, 13. 7 to 26. 0 months) in the 160 -mg group, https: //ascopubs. org/doi/full/10. 1200/JCO. 2017. 74. 7576 哆希替尼是奥希替尼的�代衍生物，�床前�效、毒理两者相当 10

显著减少N-脱甲基代谢产物的生成 10000 Mean PO(Male) Mean. . . Mean Mean Mean PO(Femal PO(Femal Mean PO(Male) Mean PO(Femal PO(Male) 2, 000 e)4, 000 e)6, 000 e) 8, 000 e)e)1, 000 PO(Male) 2, 000 8, 000 PO(Femal e)Mean 0, 500 1, 000 197, 7 195, 0 193, 0 191, 7 138, 5 0, 500 108, 10 106, 27 89, 57 PO(Male) 77, 50 e) 0, 250 67, 9 58, 10 29, 70 0, 250 15, 98, 94 1000 10 1 0 4 8 12 16 20 PO(Femal e) Mean 24, 000 PO(Male) 54, 2 24, 000 4, 31 24 Time (h) Concentration (ng/m. L) 10000 Mean Plasma Concentration of metabolite 1000 AZ 5104 -D 2 after PO Dosing of 90 -1408 100 Mean PO(Male) Mean PO(Female) Mean 10 Mean Mean PO(Femal Mean PO(Femal 1 PO(Femal PO(Male) PO(Femal PO(Male) e) 8, 00 e) 6, 00 PO(Male) e) 24, 00 e)4, 00 e) 2, 00 0, 1 6, 00 8, 00 e)1, 00 2, 00 0, 813 0, 600 0, 483 0, 458 0, 287 0, 2557 0, 2190 0, 2050 0, 01 0, 156 0, 1353 0, 0714 0, 001 0 4 8 12 16 20 24 Time (h) Mean Plasma Concentration of Mean PO(Male) Mean AZD 9291(Mesylate) after PO Dosing of Mean 1000 Mean. . . Mean PO(Femal Mean. PO(Male) AZD 9291(Mesylate) PO(Femal Mean PO(Male) PO(Femal PO(Male) 100 e) 6, 000 e) 8, 000 e) 4, 000 e)1, 000 2, 000 PO(Male) e) 6, 000 PO(Femal Mean PO(Femal 8, 000 PO(Male) 4, 000 e) 0, 500 2, 000 Mean 200, 3 187, 7 183, 0 167, 7 1, 000 119, 3 106, 43 e) 24, 000 PO(Male) 10 e)0, 500 0, 250 76, 93 72, 07 65, 7 55, 30 PO(Male) 36, 40 24, 0 0, 250 18, 7 17, 32 24, 000 1 5, 05 0 4 8 12 16 20 24 2, 79 Time (h) 10000 Mean Plasma Concentration of metabolite 1000 AZ 5104 after Dosing of AZD 9291(Mesylate) Mean PO(Male) Mean Mean 100 Mean PO(Male) Mean PO(Male) PO(Femal Mean. . . Mean PO(Male) PO(Femal Mean 10 PO(Femal Mean PO(Femal PO(Male) PO(Femal 8, 000 PO(Femal 6, 000 4, 000 e) 8, 000 Mean 2, 000 e) 6, 000 PO(Male) 1 e) 4, 000 PO(Femal e) 2, 000 1, 000 e) 24, 000 9, 2233 e) 1, 000 7, 3700 7, 3400 5, 787 PO(Male) 4, 6167 4, 537 0, 500 24, 000 2, 843 e) 1, 9053 0, 500 0, 1 1, 920 1, 897 0, 945 0, 250 0, 5490 0, 5337 0, 320 0, 01 0, 0749 0, 001 0 4 8 12 16 20 24 Time (h) Concentration (ng/m. L) Chart Title Concentration (ng/m. L) 10000 Male/female Male/Female 90 -1406 AZ 5104 -D AZD 9291 AZ 5104 Cmax (ng/m. L) 115/208 0. 256/0. 813 106/207 10. 8/5. 79 T 1/2 (h) 3. 87/6. 85 AUC 0 -last (ng·h/m. L) 1100/3105 3. 40/5. 59 2. 22/13. 7 907/2592 94. 4/79. 6 Ø N-脱甲基产物AZ 5104 -D较AZ 5104雄鼠少 98%，雌鼠少 83%。可望减少皮疹和胃肠道副作用 Ø 生物利用度提高了21. 2% （male), 19. 8% 14