GI-pediab‘å’°Šà‚̃gƒsƒbƒN‚ÉŠÖ‚·‚éƒGƒrƒfƒ“ƒX‚âî•ñ‚ð‚Ü‚Æ‚ßAŽžŒn—ñ‚È‚Ç‚É®—‚µ‚ÄЉ‚Ü‚·B

‘æ1‰ñ ‘å’°Šà‰»Šw—Ö@‚Ì•Ï‘JiisÄ”­Šàj

3. Targeted therapy
›””n —²_ æ¶AŽRú± Œ’‘¾˜Y æ¶

@2000”N‘ã‚É“ü‚èA‘å’°Šà‚̗̈æ‚É‚àŠà‚Ì‘BE“]ˆÚ‚É‚©‚©‚í‚é“Á’è‚Ì•ªŽq‚É•W“I‚ði‚Á‚½•ªŽq•W“IŽ¡—ª—Õ°“±“ü‚³‚êAŠù‘¶‚̉»Šw—Ö@‚Æ‚Ì•¹—p‚É‚æ‚Á‚ÄA‚³‚ç‚Ȃ鶑¶ŠúŠÔ‚̉„’·‚¨‚æ‚Ñ‘tŒø—¦‚ÌŒüオ}‚ç‚ꂽB‚Ü‚½AgƒoƒCƒIƒ}[ƒJ[‚É‚æ‚銳ŽÒ‘I‘ðh‚Æ‚¢‚¤ŠT”O‚ªŒ»ŽÀ‚Ì‚à‚Ì‚Æ‚È‚èApersonalized therapy‚Æ‚¢‚¤V‚½‚ÈŽž‘ã‚Ì–‹ŠJ‚¯‚ðŒ}‚¦‚½B

}5 Žå‚ȃŒƒWƒƒ“‚ƶ‘¶ŠúŠÔ -Targeted therapy
ƒNƒŠƒbƒN‚·‚é‚ƕʃEƒBƒ“ƒhƒE‚ªŠJ‚«‚Ü‚·
•\3 Žå‚ȃŒƒWƒƒ“‚ÆŠJ”­ŽžŠú -Targeted therapy
ƒNƒŠƒbƒN‚·‚é‚ƕʃEƒBƒ“ƒhƒE‚ªŠJ‚«‚Ü‚·
3.1@Bevacizumab

@ŒŒŠÇ“à”ç×–E‘BˆöŽqiVEGF: vascular endothelial growth factorj‚Í‘½‚­‚ÌŠàŽí‚Å”­Œ»‚µ‚Ä‚¢‚邱‚Æ‚ª’m‚ç‚ê‚Ä‚¨‚èA‚³‚ç‚É‚»‚Ì‚”­Œ»‚ÍŽîᇂÌZ‚â“]ˆÚAÄ”­‚¨‚æ‚Ñ—\Œã‚ÉŠÖ˜A‚·‚éBBevacizumabiƒAƒoƒXƒ`ƒ“®j‚ÍAVEGF‚ɑ΂·‚éƒLƒƒ‰Œ^ƒqƒg‰»IgG1ƒ‚ƒmƒNƒ[ƒiƒ‹R‘Ì‚Å‚ ‚èAŽîᇌŒŠÇV¶‚ð—}§‚·‚邱‚Æ‚É‚æ‚èAŽîᇂ̑B‚ ‚é‚¢‚Í“]ˆÚ‚ð—}§‚·‚邱‚Æ‚ªŠú‘Ò‚³‚ê‚éB
@ Bevacizumab‚É‹Nˆö‚·‚é“Á’¥“I‚È–ò•¨—LŠQ”½‰ž‚Æ‚µ‚Ä‚ÍAoŒŒi16.7%jAÁ‰»ŠÇúEi0.9%jAá‘Ei0.3%jAŒŒðÇðÇA‚ŒŒˆ³«”]Çi•p“x•s–¾j‚È‚Ç‚ª’m‚ç‚ê‚Ä‚¢‚é44)B

3.1.1@5-FU/LV{Bevacizumab
3.1.1 5-FU/LV{Bevacizumab
ƒNƒŠƒbƒN‚·‚é‚ƕʃEƒBƒ“ƒhƒE‚ªŠJ‚«‚Ü‚·

@Kabbinavar‚ç‚ÍABevacizumab‚𕹗p‚µ‚½3‚‚̖³ìˆ×‰»”äŠrŽŽŒ±‚̃ƒ^ƒAƒiƒŠƒVƒX‚É‚¨‚¢‚ÄA5-FU/LV‚Ü‚½‚ÍIFL‚ɑ΂µA5-FU/LV{Bevacizumab‚Í‘tŒø—¦i5-FU/LV{Bevacizumab vs. 5-FU/LV or IFL=34.1% vs. 24.5%, p=0.019jAPFSiŠeX8.8ƒ•ŒŽ vs. 5.6ƒ•ŒŽ, HR=0.63, p=0.0001jAOSiŠeX17.9ƒ•ŒŽ vs. 14.6ƒ•ŒŽ, HR=0.74, p=0.008j‚Ì‚¢‚¸‚ê‚É‚¨‚¢‚Ä‚à—LˆÓ‚Éã‰ñ‚邱‚Æ‚ðŽ¦‚µ‚½39)B5-FU/LV{Bevacizumab‚ÍACPT-11‚¨‚æ‚ÑL-OHP•s‘Ï—á‚ɑ΂·‚鎡—ÃIƒvƒVƒ‡ƒ“‚Æ”FŽ¯‚³‚ê‚Ä‚¢‚éB

3.1.2@Capecitabine{Bevacizumab

@‰‰ñŽ¡—×á‚ð‘ÎÛ‚Æ‚µ‚ÄACapecitabine’PÜ‚ÆCapecitabine{BevacizumabiCBjACapecitabine{Bevacizumab{Mitomycin C‚ð”äŠr‚µ‚½‘æIII‘ŠŽŽŒ±iMAXŽŽŒ±j‚É‚¨‚¢‚ÄACBŒQ‚ÍCapecitabine’PÜŒQ‚ɑ΂µAOS‚Å‚Í—LˆÓ·‚ð”F‚ß‚È‚©‚Á‚½‚à‚Ì‚ÌiCB vs. Capecitabine’PÜ=18.9ƒ•ŒŽ vs. 18.9ƒ•ŒŽ, HR=0.88, p=0.31jAŽå—v•]‰¿€–Ú‚Å‚ ‚éPFSiŠeX8.5ƒ•ŒŽ vs. 5.7ƒ•ŒŽ, HR=0.63, p<0.001j‚Å—LˆÓ‚Éã‰ñ‚èACapecitabine‚ɑ΂·‚éBevacizumab‚Ìã悹Œø‰Ê‚ªŽ¦‚³‚ꂽBCapecitabine{Bevacizumab‚ÍA5-FU/LV{Bevacizumab‚Æ“¯—l‚ÉACPT-11‚¨‚æ‚ÑL-OHP•s‘Ï—á‚ɑ΂·‚鎡—ÃIƒvƒVƒ‡ƒ“‚Æ‚µ‚Ä”FŽ¯‚³‚ê‚Ä‚¢‚é40)B

3.1.3@IFL{Bevacizumab
3.1.3 IFL{Bevacizumab
ƒNƒŠƒbƒN‚·‚é‚ƕʃEƒBƒ“ƒhƒE‚ªŠJ‚«‚Ü‚·

@Hurwitz‚ç‚͉‰ñŽ¡—×á‚ð‘ÎÛ‚ÉAIFL‚ðƒRƒ“ƒgƒ[ƒ‹ƒA[ƒ€‚Æ‚µ‚ÄAIFL{Bevacizumab‚Æ5-FU/LV{Bevacizumab‚Ì–³ìˆ×‰»”äŠrŽŽŒ±‚ðs‚Á‚½iAVF2107gŽŽŒ±jB’†ŠÔ‰ðÍ‚É‚¨‚¢‚ÄAIFL{Bevacizumab‚̈À‘S«‚ª”E—e‰Â”\‚Å‚ ‚Á‚½‚±‚Æ‚æ‚èA–{ŽŽŒ±‚ÍIFL‚ÆIFL{Bevacizumab‚Ì2ŒQŠÔ‚Ì”äŠrŽŽŒ±‚Æ‚µ‚ÄŒp‘±‚³‚ꂽB‚»‚ÌŒ‹‰ÊAŽå—v•]‰¿€–Ú‚Å‚ ‚éOSiIFL{Bevacizumab vs. IFL=20.3ƒ•ŒŽ vs. 15.6ƒ•ŒŽ, HR=0.66, p<0.001j‚¨‚æ‚ÑPFSiŠeX10.6ƒ•ŒŽ vs. 6.2ƒ•ŒŽ, HR=0.54, p<0.001jA‘tŒø—¦iŠeX45% vs. 35%, p=0.004j‚Ì‚¢‚¸‚ê‚É‚¨‚¢‚Ä‚àBevacizumab•¹—pŒQ‚ªã‰ñ‚Á‚½B—LŠQŽ–Û‚ÍABevacizumab•¹—pŒQ‚Å‚ŒŒˆ³‚Ì”­¶—¦‚ª—LˆÓ‚É‘½‚©‚Á‚½‚à‚Ì‚ÌA‚»‚Ì‘¼‚ɂ‚¢‚Ä‚Í—LˆÓ‚È·‚ð”F‚ß‚È‚©‚Á‚½34)B

3.1.4@FOLFOX{Bevacizumab^XELOX{Bevacizumab
3.1.4 FOLFOX{Bevacizumab
ƒNƒŠƒbƒN‚·‚é‚ƕʃEƒBƒ“ƒhƒE‚ªŠJ‚«‚Ü‚·
3.1.4 XELOX{Bevacizumab
ƒNƒŠƒbƒN‚·‚é‚ƕʃEƒBƒ“ƒhƒE‚ªŠJ‚«‚Ü‚·

ENO 16966ŽŽŒ±
iŽŽŒ±ƒfƒUƒCƒ“‚ɂ‚¢‚Ä‚Í2.2.3 XELOXŽQÆj

@Saltz‚炪•ñ‚µ‚½XELOX/FOLFOX{Bevacizumab‚ÆXELOX/FOLFOX‚Ì”äŠr‚Å‚ÍA‘tŒø—¦iŠeX47% vs. 49%, p=0.31j‚¨‚æ‚ÑOSiŠeX21.3ƒ•ŒŽ vs. 19.9ƒ•ŒŽ, HR=0.89, p=0.077j‚ɂ‚¢‚Ä‚Í—LˆÓ·‚ð”F‚ß‚È‚©‚Á‚½‚à‚Ì‚ÌAŽå—v•]‰¿€–Ú‚Å‚ ‚éPFS‚Å‚ÍBevacizumab•¹—pŒQ‚ª—LˆÓ‚Éã‰ñ‚Á‚½iŠeX9.4ƒ•ŒŽ vs. 8.0ƒ•ŒŽ, HR=0.83, p=0.0023j19)B

EE3200ŽŽŒ±

@‚Ü‚½A“ñŽŸŽ¡—ÂƂµ‚ÄA5-FU‚ÆCPT-11•s‰ž—á‚ð‘ÎÛ‚ÉFOLFOX}Bevacizumab‚Ì”äŠrŽŽŒ±‚ªs‚í‚ꂽBŽå—v•]‰¿€–Ú‚Å‚ ‚éOS‚Å‚ÍABevacizumab•¹—pŒQ‚ª—LˆÓ‚Éã‰ñ‚èiFOLFOX{Bevacizumab vs. FOLFOX=12.9ƒ•ŒŽ vs. 10.8ƒ•ŒŽ, HR=0.75, p=0.0011jAPFSiŠeX7.3ƒ•ŒŽ vs. 4.7ƒ•ŒŽ, HR=0.61Ap<0.0001jA‘tŒø—¦iŠeX22.7% vs. 8.6%, p<0.0001j‚É‚¨‚¢‚Ä‚àBevacizumab•¹—pŒQ‚ªã‰ñ‚Á‚½45)B
@ ‚±‚ê‚ç‚ÌŒ‹‰Ê‚æ‚èAˆêŽŸ‚¨‚æ‚Ñ“ñŽŸŽ¡—Âɂ¨‚¯‚éFOLFOX/XELOX‚Ö‚ÌBevacizumab•¹—p‚Ì—LŒø«‚ªŽ¦‚³‚ꂽB

3.1.5@SOX{Bevacizumab Updated

ESOFTŽŽŒ±
@SOX‚ÍAŒoŒûƒtƒb‰»ƒsƒŠƒ~ƒWƒ“Œn»Ü‚Å‚ ‚éS-1‚ÆL-OHP‚𕹗p‚·‚郌ƒWƒƒ“‚Å‚ ‚éB‰‰ñŽ¡—Âɂ¨‚¯‚é•W€Ž¡—ÂÌ1‚‚ł ‚émFOLFOX6{Bevacizumab—Ö@iFOLFOXŒQj‚ɑ΂·‚éSOX{Bevacizumab—Ö@iSOXŒQj‚Ì”ñ—ò«‚ðŒŸØ‚µ‚½–³ìˆ×‰»‘æIII‘ŠŽŽŒ±‚Å‚ ‚éSOFTŽŽŒ±‚ª–{–M‚©‚ç•ñ‚³‚ꂽB
@RECIST‚Å’è‹`‚³‚ê‚éPD‚Í•W“I•a•Ï‚ÌŬ’·Œa˜a‚©‚ç20%ˆÈã‚Ì’·Œa˜a‘‘å‚Å‚ ‚邪A–{ŽŽŒ±‚Å‚ÍPFS‚̃Cƒxƒ“ƒg‚Æ‚µ‚Ä‚ÌPD‚ðAƒx[ƒXƒ‰ƒCƒ“‚Ì•W“I•a•Ï‚Ì’·Œa˜a‚©‚ç20%ˆÈã‚Ì‘‘å‚Æ’è‹`‚µ‚½BŽå—v•]‰¿€–Ú‚Å‚ ‚éPFS‚Ì’†‰›’l‚ÍAŠÏŽ@ŠúŠÔ’†‰›’l18.4ƒ•ŒŽ‚ÌŽž“_‚ÅFOLFOXŒQ11.5ƒ•ŒŽASOXŒQ11.7ƒ•ŒŽ‚Å‚ ‚èiHR=1.043, 95% CI: 0.860-1.266jAݒ肵‚½”ñ—ò«ƒ}[ƒWƒ“1.33‚ð‰º‰ñ‚Á‚½‚½‚ßASOX—Ö@‚ÌPFS‚É‚¨‚¯‚é”ñ—ò«‚ªŽ¦‚³‚ꂽ78)B‚È‚¨A‚±‚ÌŒ‹‰Ê‚ÍRECIST‚ÉŠî‚­•]‰¿‚Å‚à“¯—l‚Å‚ ‚Á‚½B‚Ü‚½A•›ŽŸ•]‰¿€–Ú‚Å‚ ‚éOS’†‰›’l‚àA‚»‚ꂼ‚ê30.9ƒ•ŒŽA29.6ƒ•ŒŽ‚Å‚ ‚èiHR=1.052, 95% CI: 0.805-1.376jA—¼ŒQŠÔ‚É·‚ð”F‚ß‚È‚©‚Á‚½B‘tŒø—¦‚ÍAFOLFOXŒQ62.7%ASOXŒQ61.5%ip=0.8026jA8TŽž“_‚Å‚Ì‘tŒø—¦‚Í‚»‚ꂼ‚ê42.9“A40.3%ip=0.5669) 79)AÅ‘åŽîá‡k¬Š„‡‚Í‚»‚ꂼ‚ê71.7%A72.3%ip=0.8944jAR0Øœ—¦‚Í‚»‚ꂼ‚ê8.6%A9.4%ip=0.7678j78)‚ÆA—¼ŒQŠÔ‚É·‚ð”F‚ß‚È‚©‚Á‚½B
@Grade 3ˆÈã‚ÌŽå‚È—LŠQŽ–Û‚Æ‚µ‚ÄFOLFOXŒQ‚ÅD’†‹…”Œ¸­ASOXŒQ‚ÅÁ‰»Ší“Å«i”S–Œ‰ŠAH—~•sUA‰º—Ÿj‚ª‘½‚¢ŒXŒü‚É‚ ‚Á‚½B‚Ü‚½A–{ŽŽŒ±‚É‚¨‚¢‚Ä‚ÍFOLFOXŒQ‚Å1—ái0.4%jASOXŒQ‚Å5—ái2.0%j‚ÌÁ‰»ŠÇúE—á‚ð”F‚ß‚½‚ªA–¾‚ç‚©‚È• –Œ“]ˆÚ‚ð—L‚·‚éÇ—á‚Æ‚“x‚ÌÁ‰»ŠÇ‹·ó‚ð”F‚ß‚éÇ—á‚ðœŠO‚·‚邱‚ƂňÈ~‚Ì”­¶‚ð‰ñ”ð‚·‚é‚±‚Æ‚ª‚Å‚«‚½B
@ˆÈã‚©‚çA‰‰ñŽ¡—ÂƂµ‚ÄSOX{Bevacizumab‚ÍŽ¡—ÑI‘ðŽˆ‚Ì1‚‚ł ‚é‚Æl‚¦‚ç‚ê‚éB

3.1.6@FOLFIRI{Bevacizumab

@Fuchs‚ç‚ÍA‰‰ñŽ¡—×á‚ð‘ÎÛ‚ÉAmodified IFLimIFLj{Bevacizumab‚ÆFOLFIRI{Bevacizumab‚ð”äŠr‚µ‚½‘æII‘ŠŽŽŒ±iBICC-CŽŽŒ± Period 2j‚ðs‚¢A‘tŒø—¦iFOLFIRI{Bevacizumab vs. mIFL{Bevacizumab=57.9% vs. 53.3%jAPFSiŠeX11.2ƒ•ŒŽ vs. 8.3ƒ•ŒŽ. p=0.28j‚É‚¨‚¢‚Ä‚Í—LˆÓ·‚Í”F‚ß‚È‚©‚Á‚½‚à‚Ì‚ÌAOS‚ÍFOLFIRI{Bevacizumab‚ªã‰ñ‚邱‚ÆiŠeX28.0ƒ•ŒŽ vs. 19.2ƒ•ŒŽ, p=0.037j‚ð•ñ‚µ‚½B
@ –{•ñ‚æ‚èABevacizumab‚Æ•¹—p‚·‚éÛ‚Ì5-FU/LV{CPT-11ƒŒƒWƒƒ“‚ÍFOLFIRI‚ªÅ“K‚Å‚ ‚é‚Æ”FŽ¯‚³‚ê‚Ä‚¢‚é27)B

3.1.7@FOLFOXIRI{Bevacizumab@Updated

ETRIBEŽŽŒ±
@TRIBEŽŽŒ±‚Å‚ÍA‰‰ñŽ¡—Âɂ¨‚¯‚éFOLFIRI{Bevacizumab‚ÆFOLFOXIRI{Bevacizumab‚ª”äŠr‚³‚ꂽBFOLFOXIRIŒQ‚Ì—p—Ê‚ÍACPT-11: 165mg/m2AL-OHP: 85mg/m2ALV: 200mg/m2A5-FU ci: 3,200mg/m2ABevacizumab: 5mg/kg‚Å‚ ‚èAFOLFIRIŒQAFOLFOXIRIŒQ‚Æ‚à‚ÉÅ‘å12ƒTƒCƒNƒ‹“Š—^‚µ‚½ŒãA5-FU/LV{Bevacizumab‚É‚æ‚éˆÛŽ—Ö@‚ðs‚Á‚½B
@ŠÏŽ@ŠúŠÔ’†‰›’l32.3ƒ•ŒŽ‚ÌŽž“_‚ÅAPFS’†‰›’l‚ÍFOLFIRIŒQ9.7ƒ•ŒŽAFOLFOXIRIŒQ12.1ƒ•ŒŽ‚ÆAFOLFOXIRIŒQ‚Å—LˆÓ‚ȉ„’·‚ð”F‚ß‚½iHR=0.77, 95% CI: 0.64-0.93, p=0.006j80)B‚Ü‚½AOS’†‰›’l‚Í‚»‚ꂼ‚ê25.8ƒ•ŒŽA31.0ƒ•ŒŽ‚ÆAFOLFOXIRIŒQ‚Å—ÇD‚ÈŒXŒü‚ð”F‚ß‚½iHR=0.83, 95% CI: 0.66-1.05, p=0.125jBˆâ“`Žq•ÏˆÙ•Ê‚ÌPFS‚ÌHR‚ÍAKRAS exon 2–춌^/•ÏˆÙŒ^‚Å0.83/0.84ABRAF–춌^/•ÏˆÙŒ^‚Å0.83/0.55‚ÆAˆâ“`Žq•ÏˆÙ‚Ì—L–³‚É‚©‚©‚í‚炸FOLFOXIRIŒQ‚Ì—LŒø«‚ªŽ¦´‚³‚êA‚Æ‚è‚킯—\Œã‚ª•s—Ç‚ÈBRAF•ÏˆÙŒ^‚É‚¨‚¯‚é—LŒø«‚ªŠú‘Ò‚³‚ê‚錋‰Ê‚Å‚ ‚Á‚½B
@‘tŒø—¦‚ÍFOLFIRIŒQ53%AFOLFOXIRIŒQ65%‚ÆFOLFOXIRIŒQ‚Å—LˆÓ‚É—ÇD‚Å‚ ‚Á‚½‚ªip=0.006jAŠÌŒÀ‹Ç“]ˆÚ—á‚É‚¨‚¯‚éconversion therapy‚ÌŠ„‡‚¨‚æ‚ÑR0Øœ—¦‚Í—¼ŒQŠÔ‚Å—LˆÓ·‚ð”F‚ß‚È‚©‚Á‚½B‚È‚¨A‘ŠúŽîá‡k¬‚Æ‘tŒø‚Ì[‚³‚É‚æ‚錟“¢‚Å‚ÍA‘ŠúŽîá‡k¬‚𓾂½Ç—á‚Å‚ÍA“¾‚È‚©‚Á‚½Ç—á‚Æ”äŠr‚µ‚ÄPFS‚̉„’·‚ð”F‚ßip < 0.0001jAÅ‘åŽîá‡k¬Š„‡‚Ì’†‰›’l (38.9%) ‚ð’´‚¦‚éŽîá‡k¬‚𓾂½Ç—á‚ÍA’†‰›’lˆÈ‰º‚Å‚ ‚Á‚½Ç—á‚Æ”äŠr‚µ‚ÄPFS‚̉„’·‚ð”F‚ß‚½ip<0.0001j81)B
@Žå‚Ègrade 3ˆÈã‚Ì—LŠQŽ–Û‚ÍAD’†‹…”Œ¸­‚¨‚æ‚Ñ––½_ŒoáŠQ‚ªFOLFOXIRIŒQ‚Å—LˆÓ‚É‘½‚©‚Á‚½‚à‚Ì‚Ìi‚Æ‚à‚Ép<0.001jA”­”M«D’†‹…Œ¸­Ç‚Í“¯’ö“x‚ÅA‚»‚Ì‘¼‚Ì”ñŒŒ‰t“Å«‚à—¼ŒQŠÔ‚Å·‚ð”F‚ß‚¸A”E—e‰Â”\‚Å‚ ‚é‚Æl‚¦‚ç‚ꂽB
@ˆÈã‚©‚çA‰‰ñŽ¡—ÂÌA“Á‚ÉRAS•ÏˆÙ‚ð—L‚µREGFRR‘Ì–ò‚ÌŒø‰Ê‚ªŠú‘Ò‚Å‚«‚È‚¢Ç—á‚É‚¨‚¢‚ÄFOLFOXIRI{Bevacizumab‚ÍAOS‚̉„’·‚ðŠú‘Ò‚µ“¾‚é—L–]‚ȃŒƒWƒƒ“‚Å‚ ‚é‚Æl‚¦‚ç‚ê‚éB‚½‚¾‚µOS‚̉ð͂ɂ‚¢‚Ä‚ÍŠÏŽ@ŠúŠÔ‚ª\•ª‚Å‚Í‚È‚­A2nd-lineˆÈ~‚̉e‹¿‚É‚æ‚èPFS‚Ì·‚ªOS‚É‚¨‚¢‚Ă͈ێ‚Å‚«‚È‚¢‰Â”\«‚ð”O“ª‚É‚¨‚­•K—v‚ª‚ ‚éB

3.1.8@Bevacizumab beyond progression

EBRiTEAARIESiŠÏŽ@Œ¤‹†j

@Bevacizumab•¹—p‰»Šw—Ö@‚É‚æ‚鉉ñŽ¡—Âɕs‰ž‚Æ‚È‚Á‚½ŒãA“ñŽŸŽ¡—ÂÅBevacizumab‚ðŒp‘±‚µ‚Ä•¹—p‚·‚邱‚Æ (bevacizumab beyond progression: BBP) ‚Ì—L—p«‚ÍABRiTE‚¨‚æ‚ÑARIES‚Æ‚¢‚¤2‚‚̑å‹K–ÍŠÏŽ@Œ¤‹†‚É‚æ‚Á‚ÄŽ¦´‚³‚ê‚Ä‚¢‚½BBRiTE‚É‚¨‚¯‚éOS‚ÍBBPŒQ31.8ƒ•ŒŽA”ñBBPŒQ19.9ƒ•ŒŽ‚ÆABBPŒQ‚Ŷ‘¶ŠúŠÔ‚ª—ÇD‚ÅA‘±‚¢‚Ä•ñ‚³‚ꂽARIES‚É‚¨‚¢‚Ä‚àOS‚ÍBBPŒQ27.5ƒ•ŒŽA”ñBBPŒQ18.7ƒ•ŒŽ‚ÆABRiTE‚ÌŒ‹‰Ê‚ðŽxŽ‚·‚錋‰Ê‚Å‚ ‚Á‚½62, 63)B

EML18147ŽŽŒ±

@ML18147ŽŽŒ±‚ÍBBP‚Ì—LŒø«‚ð‘OŒü‚«‚ÉŒŸØ‚µ‚½–³ìˆ×‰»”äŠr‘æIII‘ŠŽŽŒ±‚Å‚ ‚éB•W€“I‚ÈBevacizumab•¹—p‚̉‰ñŽ¡—Õs‰ž—á‚ð‘ÎÛ‚ÉA“ñŽŸŽ¡—Âɂ¨‚¯‚éBevacizumab•¹—pŒQiBBPŒQj‚Æ”ñ•¹—pŒQi”ñBBPŒQj‚ð–³ìˆ×‰»”äŠr‚µ‚½i}7jBŽå—v•]‰¿€–Ú‚Å‚ ‚éOS‚Ì’†‰›’l‚ÍBBPŒQ 11.2ƒ•ŒŽA”ñBBPŒQ9.8ƒ•ŒŽiHR=0.81, 95% CI: 0.69-0.94, p=0.0062j‚ÆA—LˆÓ‚ÉBBPŒQ‚ª—ÇD‚Å‚ ‚Á‚½64)B•›ŽŸ•]‰¿€–Ú‚Å‚ÍA‘tŒø—¦‚É—LˆÓ·‚ð”F‚ß‚È‚©‚Á‚½‚à‚Ì‚Ìi5.4% vs. 3.9%, p=0.3113jAPFS‚ÍBBPŒQ‚Å—LˆÓ‚ɉ„’·‚µ‚½i5.7ƒ•ŒŽ vs. 4.1ƒ•ŒŽAHR=0.68, 95% CI: 0.59-0.78, p<0.0001jBƒTƒuƒOƒ‹[ƒv‰ðÍ‚Å‚ÍKRAS•ÏˆÙ‚Ì—L–³‚ɂ‚¢‚Ä‚Ìî•ñ‚ª“¾‚ç‚ꂽǗá‚ð‘ÎÛ‚ÉAKRAS status•Ê‚ÉBBP‚ÌŒø‰Ê‚ª‰ðÍ‚³‚ꂽBPFS‚ÍKRAS–춌^‚É‚¨‚¢‚ÄBBPŒQ6.4ƒ•ŒŽA”ñBBPŒQ4.5ƒ•ŒŽiHR=0.61, 95% CI: 0.49-0.77, p<0.0001jAKRAS•ÏˆÙŒ^‚É‚¨‚¢‚ÄBBPŒQ5.5ƒ•ŒŽA”ñBBPŒQ4.1ƒ•ŒŽiHR=0.70, 95% CI: 0.56-0.89, p=0.0027j‚ÆAKRAS status‚É‚æ‚炸BBP‚É‚æ‚éPFS‚̉„’·Œø‰Ê‚ªŽ¦‚³‚ꂽ‚ªAOS‚ÍKRAS–춌^‚Å‚Í—LˆÓ·‚ð”F‚ß‚½‚à‚Ì‚Ìi15.4ƒ•ŒŽ vs. 11.1ƒ•ŒŽ, HR=0.69, p=0.0052)AKRAS•ÏˆÙŒ^‚É‚¨‚¢‚Ä‚Í—LˆÓ·‚ð”F‚ß‚È‚©‚Á‚½i10.4ƒ•ŒŽ vs. 10.0ƒ•ŒŽ, HR=0.92, p=0.4969j65)B‚Ü‚½AESMO 2012‚Å‚Í”N—î•Ê‚̉ðÍ‚ª”­•\‚³‚êAOS‚Í65Ζ¢–ž‚É‚¨‚¢‚ÄBBPŒQ11.6ƒ•ŒŽA”ñBBPŒQ9.9ƒ•ŒŽiHR=0.79, 95% CI: 0.65-0.98, p=0.0274jA65ΈÈã‚Å‚ÍBBPŒQ10.7ƒ•ŒŽA”ñBBPŒQ9.8ƒ•ŒŽiHR=0.83, 95% CI: 0.66-1.04, p=0.1056j‚ÆA”N—î‚É‚æ‚炸BBPŒQ‚Å—ÇD‚Å‚ ‚Á‚½66)B
@ˆÈã‚ÌŒ‹‰Ê‚æ‚èABBP‚Í•W€“I‚ÈŽ¡—Ãí—ª‚Ì1‚‚Æl‚¦‚ç‚êANCCNƒKƒCƒhƒ‰ƒCƒ“ i2013”N”ÅAversion1j‚É‚àŒfÚ‚³‚ê‚é‚悤‚É‚È‚Á‚½67)B‚½‚¾‚µAML18147ŽŽŒ±‚Ì‘Îۂ͉‰ñŽ¡—ÂÌPFS‚ª3ƒ•ŒŽˆÈã‚Å‚ ‚èA‰‰ñŽ¡—Âɂ¨‚¯‚éBevacizumab‚ª˜A‘±‚µ‚Ä3‰ñˆÈã“Š—^‚³‚êA‚©‚ÂBevacizumabÅI“Š—^Œã3ƒ•ŒŽˆÈ“à‚É‘ˆ«‚µ‚½Ç—Ⴊ‘ÎÛ‚Æ‚È‚Á‚Ä‚¢‚邱‚Æ‚ð”O“ª‚É’u‚­•K—v‚ª‚ ‚éB

EBEBYPŽŽŒ±

@2012”N‚ÌESMO‚ł̓Cƒ^ƒŠƒA‚æ‚èML18147ŽŽŒ±‚É‘ŠŽ—‚µ‚½ƒfƒUƒCƒ“‚Ì–³ìˆ×‰»”äŠr‘æII‘ŠŽŽŒ± iBEBYPŽŽŒ±j‚ÌŒ‹‰Ê‚ª•ñ‚³‚ꂽB‚±‚ÌŽŽŒ±‚ÍML18147ŽŽŒ±‚ÌŒö•\‚¨‚æ‚ÑÇ—áWÏ‚Ì’x‚ê‚©‚玎Œ±‚ª“r’†’†Ž~‚Æ‚È‚Á‚½‚ªAŽå—v•]‰¿€–Ú‚Å‚ ‚éPFS‚ÍBBPŒQ6.77ƒ•ŒŽA”ñBBPŒQ4.97ƒ•ŒŽiHR=0.65, 95% CI: 0.48-0.89, p=0.0062j‚ÆA—LˆÓ‚ÉBBPŒQ‚ª—ÇD‚Å‚ ‚Á‚½68)B‚È‚¨A•›ŽŸ•]‰¿€–Ú‚Ì‘tŒø—¦‚ÍBBPŒQ21%A”ñBBPŒQ18%ip=0.71j‚Æ—¼ŒQ‚Å·‚ð”F‚ß‚¸AOS‚Í\•ª‚ȃCƒxƒ“ƒg”‚É’B‚µ‚Ä‚¢‚È‚¢‚½‚ߌö•\‚³‚ê‚È‚©‚Á‚½B

}7 ML18147 study design(phase‡V)
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3.2@Cetuximab

@ã”ç×–E‘BˆöŽqŽó—e‘ÌiEGFR: Epidermal growth factor receptorj‚ÍAã”ç×–E‚È‚Ç‚É”­Œ»‚·‚é–ŒŠÑ’ÊŒ^‚ÌŽó—e‘Ì‚Å‚ ‚èAƒŠƒKƒ“ƒh‚ªŒ‹‡‚·‚é‚ÆEGFRƒ`ƒƒVƒ“ƒLƒi[ƒ[‚ªŠˆ«‰»‚³‚êA×–E“àƒVƒOƒiƒ‹“`’B‚ð‰î‚µ‚Ä×–E‘B‚╪‰»‚ª‘£i‚³‚ê‚éBCetuximabiƒA[ƒrƒ^ƒbƒNƒX®j‚ÍAEGFR‚ɑ΂·‚éIgG1ƒTƒuƒNƒ‰ƒX‚̃qƒg/ƒ}ƒEƒXƒLƒƒ‰Œ^‚̃‚ƒmƒNƒ[ƒiƒ‹R‘Ì‚ÅAEGFR‚ÉŒ‹‡‚·‚邱‚Æ‚É‚æ‚èA×–E‘B‚â“]ˆÚ‚Ì—}§‚ªŠú‘Ò‚³‚ê‚éB
@ Cetuximab‚É‚æ‚é–ò•¨—LŠQ”½‰ž‚Æ‚µ‚ÄAd“x‚Ìinfusion reactioni<5%jAd“x‚̔畆áŠQi10`15%jAŠÔŽ¿«”xŽ¾Š³i<0.5%jA’áƒ}ƒOƒlƒVƒEƒ€ŒŒÇA‰º—Ÿ‚È‚Ç‚ª•ñ‚³‚ê‚Ä‚¢‚é46)B

Eƒƒ‚FREGFRR‘Ì–ò‚ÌRŽîᇌø‰Ê‚ÆEGFR”­Œ»

@“–‰AREGFRR‘Ì–ò‚Í‚»‚Ìì—p‹@˜‚æ‚èA–Ɖu‘gD‰»ŠwõFiIHCj‚ÅEGFR‚ð”­Œ»‚µ‚Ä‚¢‚é‘å’°Šà‚ð‘ÎÛ‚ÉŠJ”­‚³‚ê‚Ä‚«‚½‚ªA‚»‚ÌŒã‚̉ðÍ‚É‚æ‚èAIHC‚É‚æ‚éEGFR”­Œ»‚Ì’ö“xiEGFR×–E–ŒõF‚ÌŠ„‡AEGFR×–E–ŒõF‹­“xj‚ÆREGFRR‘Ì–ò‚ÌRŽîᇌø‰Ê‚É‚Í–¾‚ç‚©‚È‘ŠŠÖ‚ð”F‚ß‚È‚¢‚Æ‚Ì•ñ47, 48)‚ª‚È‚³‚êAIHC‚É‚æ‚éEGFR”­Œ»‚Ì—L–³‚ÍREGFRR‘Ì‚ðŽg—p‚·‚éÛ‚Él—¶‚µ‚È‚­‚Ä‚æ‚¢‚Æl‚¦‚ç‚ê‚é‚悤‚É‚È‚Á‚Ä‚¢‚éB

Eƒƒ‚FREGFRR‘Ì–ò‚ÌRŽîᇌø‰Ê‚ÆKRASˆâ“`Žq

@EGFR×–E“àƒVƒOƒiƒ‹“`’BŒo˜H‚Ì1‚‚ł ‚éKRAS/RAF/MAPK“`’BŒo˜H‚É‚¨‚¢‚ÄAKRASˆâ“`Žq‚É“_“Ë‘R•ÏˆÙ‚ª‹N‚±‚é‚Ɖº—¬‚Ö‚ÌPí“I‚ȃVƒOƒiƒ‹“`’B‚ª‹N‚±‚èAEGFR‘jŠQ‚É‚æ‚éRŽîᇌø‰Ê‚ª–³Œø‚É‚È‚é‚Æl‚¦‚ç‚ê‚Ä‚¢‚éBREGFRR‘Ì–ò‚ð—p‚¢‚½‘½”‚Ì—Õ°ŽŽŒ±‚̉ðÍ‚©‚ç‚à“¯—l‚Ì•ñ‚ªs‚í‚êAŒ»ÝAKRASˆâ“`Žq•ÏˆÙ‚ð—L‚·‚éÇ—á‚ɑ΂·‚éREGFRR‘Ì–ò‚Ì“Š—^‚Í„§‚³‚ê‚Ä‚¢‚È‚¢B

3.2.1@Cetuximab’PÜ
3.2.1 Cetuximab’PÜ
ƒNƒŠƒbƒN‚·‚é‚ƕʃEƒBƒ“ƒhƒE‚ªŠJ‚«‚Ü‚·

@NCI CTG CO.17ŽŽŒ±‚Å‚ÍAƒtƒb‰»ƒsƒŠƒ~ƒWƒ“‚¨‚æ‚ÑCPT-11AL-OHP‚É•s‰ž‚Æ‚È‚Á‚½Ç—á‚ɑ΂µABSC‚Æ‚Ì”äŠr‚ÅŽå—v•]‰¿€–Ú‚Å‚ ‚éOSiCetuximab vs. BSC=6.1ƒ•ŒŽ vs. 4.6ƒ•ŒŽ, HR=0.77, p=0.005jA‚¨‚æ‚ÑPFSiŠeX1.9ƒ•ŒŽ vs. 1.8ƒ•ŒŽ, HR=0.68, p<0.001jA‘tŒø—¦iŠeX8% vs. 0%, p<0.001j‚É‚¨‚¢‚Ä—LˆÓ‚Éã‰ñ‚èA‘å’°Šà‚É‚¨‚¯‚éCetuximab’PÜ“Š—^‚Ì—LŒø«‚ªŽ¦‚³‚ꂽ49)B
@‚»‚ÌŒãAKRASˆâ“`Žq•ÏˆÙ—L–³•Ê‚̃ŒƒgƒƒXƒyƒNƒeƒBƒu‚ȉðÍ‚ªs‚í‚êAKRAS–춌^‚Å‚ÍOS‚ÍŠeX9.5ƒ•ŒŽ vs. 4.8ƒ•ŒŽiHR=0.55, p<0.001jAPFS‚ÍŠeX3.7ƒ•ŒŽ vs. 1.9ƒ•ŒŽiHR=0.40, p<0.001jA‘tŒø—¦‚Í12.8% vs. 0%‚Æ—LŒø«‚ªŽ¦‚³‚ꂽBˆê•ûAKRASˆâ“`Žq•ÏˆÙŒ^‚Å‚ÍOS‚ÍŠeX4.5ƒ•ŒŽ vs. 4.6ƒ•ŒŽiHR=0.98, p=0.89jAPFS‚ÍŠeX1.8ƒ•ŒŽ vs. 1.8ƒ•ŒŽiHR=0.99, p=0.96jA‘tŒø—¦‚Í1.2% vs. 0%‚Æ—LŒø«‚ð”F‚ß‚È‚©‚Á‚½50)B
@ —LŠQŽ–ۂɂ‚¢‚Ä‚ÍA”ç]A’áƒ}ƒOƒlƒVƒEƒ€ŒŒÇ“™‚Ì•p“x‚ªCetuximabŒQ‚Å—LˆÓ‚É‘½‚©‚Á‚½49)B

3.2.2@CPT-11{Cetuximab
3.2.2 CPT-11{Cetuximab
ƒNƒŠƒbƒN‚·‚é‚ƕʃEƒBƒ“ƒhƒE‚ªŠJ‚«‚Ü‚·

EEPICŽŽŒ±

@EPICŽŽŒ±‚Å‚ÍA5-FUAL-OHP•s‰ž—á‚ɑ΂·‚éCPT-11‚Ö‚ÌCetuximab‚Ìã悹Œø‰Ê‚ªŒŸ“¢‚³‚ꂽB‚»‚ÌŒ‹‰ÊAPFS‚Å‚ÍCPT-11{CetuximabŒQ‚ª—LˆÓ‚Éã‰ñ‚Á‚½‚à‚Ì‚ÌiCPT-11{Cetuximab vs. CPT-11=4.0ƒ•ŒŽ vs. 2.6ƒ•ŒŽ, HR=0.69, p≤0.0001jAŽå—v•]‰¿€–Ú‚Å‚ ‚éOS‚ɂ‚¢‚Ä‚Í—¼Ž¡—ÃŒQŠÔ‚Å·‚ª‚‚©‚È‚©‚Á‚½iŠeX10.7ƒ•ŒŽ vs. 10.0ƒ•ŒŽ, HR=0.98, p=0.71jB‚±‚ê‚ÍACPT-11’P“ÆŒQ‚Ì–ñ47%‚Ō㎡—ÂƂµ‚ÄCetuximab‚ªŽg—p‚³‚ꂽ‚±‚Æ‚É‚æ‚é‚Æl‚¦‚ç‚ê‚Ä‚¢‚é51)B
@–{Œ‹‰Ê‚æ‚èA¶‘¶ŠúŠÔ‚ÌŠÏ“_‚©‚ç‚ÍCetuximab‚Ì“±“üŽžŠú‚Í“ñŽŸŽ¡—ÃAŽOŽŸŽ¡—Â̂¢‚¸‚ê‚Å‚à‚æ‚¢‚Æl‚¦‚ç‚ê‚Ä‚¢‚éB

EBONDŽŽŒ±

@BONDŽŽŒ±‚Å‚ÍACPT-11•s‰ž—á‚ɑ΂·‚éCPT-11{Cetuximab‚ÆCetuximab’PÜ‚ª”äŠr‚³‚ꂽBOS‚Å‚Í—LˆÓ·‚ð”F‚ß‚È‚¢‚à‚Ì‚ÌACPT-11•¹—pŒQ‚Å—ÇD‚ÈŒXŒü‚ð”F‚ßiCPT-11{Cetuximab vs. CPT-11=8.6ƒ•ŒŽ vs. 6.9ƒ•ŒŽ, HR=0.91, p=0.48jAŽå—v•]‰¿€–Ú‚Å‚ ‚é‘tŒø—¦iŠeX23% vs. 11%, p=0.007j‚¨‚æ‚ÑTTPiŠeX4.1ƒ•ŒŽ vs. 1.5ƒ•ŒŽ, HR=0.54, p<0.001j‚É‚¨‚¢‚ÄCPT-11•¹—pŒQ‚ª—LˆÓ‚Éã‰ñ‚Á‚½B‚»‚ÌŒ‹‰ÊACPT-11•s‰ž—á‚ɑ΂µ‚Ä‚àCPT-11{Cetuximab‚ªCetuximab’PÜ‚æ‚è‚à—LŒø‚Å‚ ‚邱‚Æ‚ªŽ¦‚³‚ê52)ACPT-11•s‘Ï—á‚Å‚È‚¯‚ê‚ÎCPT-11‚𕹗p‚·‚邱‚Æ‚ª„§‚³‚ê‚Ä‚¢‚éB

3.2.3@FOLFIRI{Cetuximab Updated
3.2.3@FOLFIRI{Cetuximab
ƒNƒŠƒbƒN‚·‚é‚ƕʃEƒBƒ“ƒhƒE‚ªŠJ‚«‚Ü‚·

ECRYSTALŽŽŒ±
@CRYSTALŽŽŒ±‚Å‚ÍA‰‰ñŽ¡—Âð‘ÎÛ‚ÉFOLFIRI‚ɑ΂·‚éCetuximab‚Ìã悹Œø‰Ê‚ªŒŸ“¢‚³‚ꂽBKRASˆâ“`Žq•ÏˆÙ—á‚ðŠÜ‚Þ‘S‘Ì‚Å‚ÍAOS‚É‚¨‚¢‚Ä‚Í—LˆÓ·‚ª‚È‚©‚Á‚½‚à‚Ì‚ÌiFOLFIRI{Cetuximab vs. FOLFIRI=19.9ƒ•ŒŽ vs. 18.6ƒ•ŒŽ, HR=0.93, p=0.31jAŽå—v•]‰¿€–Ú‚Å‚ ‚éPFS‚ÍACetuximab•¹—pŒQ‚ª—LˆÓ‚É—ÇD‚Å‚ ‚Á‚½iŠeX8.9ƒ•ŒŽ vs. 8.0ƒ•ŒŽ, HR=0.85, p=0.048jB
@‚»‚ÌŒãAKRASˆâ“`Žq•ÏˆÙ—L–³•Ê‚̃ŒƒgƒƒXƒyƒNƒeƒBƒu‚ȉðÍ‚ªs‚í‚êAKRAS–춌^‚Å‚ÍPFSiŠeX9.9ƒ•ŒŽ vs. 8.7ƒ•ŒŽ, HR=0.68, p=0.02jAOSiŠeX24.9ƒ•ŒŽ vs. 21.0ƒ•ŒŽ, HR=0.84jA‘tŒø—¦iŠeX59% vs. 43%, ƒIƒbƒY”ä1.91j‚Ì‚·‚ׂĂÌRŽîᇌø‰Ê‚Å—LˆÓ‚ÉCetuximab•¹—pŒQ‚ªã‰ñ‚Á‚½‚ªAKRASˆâ“`Žq•ÏˆÙŒ^‚Å‚ÍPFSiŠeX7.6ƒ•ŒŽ vs. 8.1ƒ•ŒŽ, HR=1.07, p=0.75jAOSiŠeX17.5ƒ•ŒŽ vs. 17.7ƒ•ŒŽ, HR=1.03jA‘tŒø—¦iŠeX36% vs. 40%, ƒIƒbƒY”ä0.80j‚ÆCetuximab‚Ìã悹Œø‰Ê‚ÍŽ¦‚¹‚È‚©‚Á‚½53)B‚±‚ÌŒ‹‰Ê‚æ‚èAKRASˆâ“`Žq–춌^‚̉‰ñŽ¡—×á‚ɑ΂·‚éCetuximab‚Ìã悹Œø‰Ê‚ªŽ¦‚³‚ꂽB
EFIRE-3ŽŽŒ±
@FIRE-3ŽŽŒ±‚Å‚ÍA‰‰ñ‰»Šw—Ö@‚É‚¨‚¢‚ÄAFOLFIRI—Ö@‚ðƒx[ƒX‚Æ‚µ‚ÄCetuximab‚ÆBevacizumab‚ª’¼Ú”äŠr‚³‚ꂽBŽŽŒ±ŠJŽnŽž‚É‚ÍKRAS status‚É‚æ‚炸“o˜^‚ªs‚í‚ꂽ‚ªAŒã‚ÉKRAS exon 2–춌^‚ÉŒÀ’肵‚Ä“o˜^‚³‚êAŽå‰ðÍ‚Ì‘ÎÛ‚Æ‚È‚Á‚Ä‚¢‚éB
@Žå—v•]‰¿€–Ú‚Å‚ ‚é‘tŒø—¦‚ÍACetuximabŒQ62.0%ABevacizumabŒQ58.0%‚ÅA—¼ŒQŠÔ‚É—LˆÓ·‚ð”F‚ß‚È‚©‚Á‚½iodds ratio=1.18, 95% CI: 0.85-1.64, p=0.183j82)B‚Ü‚½APFS’†‰›’l‚Í‚»‚ꂼ‚ê10.0ƒ•ŒŽA10.3ƒ•ŒŽ‚Æ“¯’ö“x‚Å‚ ‚Á‚½‚à‚Ì‚ÌiHR=1.06, 95% CI: 0.88-1.26, p=0.547jAOS’†‰›’l‚Í‚»‚ꂼ‚ê28.7ƒ•ŒŽA25.0ƒ•ŒŽ‚ÆACetuximabŒQ‚Å—LˆÓ‚ȉ„’·‚ð”F‚ß‚½iHR=0.77, 95% CI: 0.62-0.96, p=0.017jB‚È‚¨AKRAS exon 2ˆÈŠO‚ÌRASˆâ“`Žq•ÏˆÙA‚·‚È‚í‚¿KRAS exon 3, 4ANRAS exon 2, 3, 4‘S‚Ăɕψقð—L‚³‚È‚¢Ç—áiRAS–춌^j‚ð‘ÎÛ‚Æ‚·‚é‚ÆAOS’†‰›’l‚ÍCetuximabŒQ33.1ƒ•ŒŽABevacizumabŒQ25.6ƒ•ŒŽ‚ÆA—¼ŒQ‚Ì·‚Í‚æ‚è‘å‚«‚­‚È‚Á‚½iHR=0.70, 95% CI: 0.53-0.92, p=0.011j83)B‹t‚ÉAKRAS exon 2–춌^‚©‚ÂRAS•ÏˆÙŒ^‚É‚¨‚¢‚Ä‚ÍACetuximabŒQ‚ÅPFS‚ª—LˆÓ‚É’Z‚­iHR=2.22, p=0.004jAOS‚à’Z‚¢ŒXŒü‚ª‚Ý‚ç‚ꂽiHR=1.20, p=0.57jB
@Grade 3ˆÈã‚ÌŽå‚È—LŠQŽ–Û‚Æ‚µ‚ÄACetuximabŒQ‚Ŕ畆áŠQiŽè‘«ÇŒóŒQA‚´áŒ—l”ç]j‚â’áƒ}ƒOƒlƒVƒEƒ€ŒŒÇAinfusion reaction‚ð‚æ‚葽‚­”F‚ß‚½‚à‚Ì‚Ì82)A‹–—e‚³‚ê‚é”͈͓à‚Æl‚¦‚ç‚ꂽB‘¼‚Ì—LŠQŽ–ۂɂ‚¢‚Ä‚Í—¼ŒQ‚Å·‚ð”F‚ß‚È‚©‚Á‚½B
@‘tŒø—¦‚âPFS‚Å·‚ª‚‚©‚¸AOS‚Å‚Ì‚Ý—LˆÓ·‚ª‚‚¢‚½——R‚Í–¾Šm‚Å‚Í‚È‚¢‚ªAPEAKŽŽŒ±‚ÌŒ‹‰Ê‚Ƈ‚킹ARAS–춌^‚̉‰ñŽ¡—Âɂ¨‚¢‚ÄREGFRR‘Ì–ò•¹—p—Ö@‚ªBevacizumab•¹—p—Ö@‚æ‚è‚àOS‚̉„’·‚ÉŠñ—^‚·‚é‰Â”\«‚ªŽ¦´‚³‚ꂽB‚½‚¾‚µAOS‚Í–{ŽŽŒ±‚ÌŽå—v•]‰¿€–Ú‚Å‚Í‚È‚¢‚±‚ÆABevacizumab•¹—pŒQ‚ÅBBPibevacizumab beyond progressionj‚ªs‚í‚ꂽǗႪ­‚È‚¢‚±‚Æ‚È‚ÇAŒ»Žž“_‚ÅREGFRR‘Ì–ò‚Ì—D‰z«‚ª–¾Šm‚Å‚ ‚é‚Æ‚ÍŒ¾‚¢Ø‚ê‚È‚¢B¡ŒãA•ñ‚³‚ê‚é—\’è‚Ì“¯—l‚̃Rƒ“ƒZƒvƒg‚Å‚ ‚éCALGB80405ŽŽŒ±‚ÌŒ‹‰Ê‚𓥂܂¦A‹c˜_‚ðs‚¤‚ׂ«‚Å‚ ‚낤B‚Ü‚½PEAKŽŽŒ±APRIMEŽŽŒ±‚̒ljÁ‰ðÍŒ‹‰Ê‚Ƈ‚킹AREGFRR‘Ì–ò‚ÌŽg—p‚ÍRAS–춌^‚Éi‚é‚ׂ«‚Æl‚¦‚ç‚ê‚邪A–{–M‚É‚¨‚¢‚Ä‘Oq‚ÌRASŒŸ¸‚Í•ÛŒ¯“K‰žŠO‚Å‚ ‚èi2013”N11ŒŽŒ»ÝjAƒŒƒWƒƒ“‘I‘ð‚Ìá•Ç‚Æ‚È‚Á‚Ä‚¢‚éB

3.2.4@FOLFOX{Cetuximab
3.2.4@FOLFOX{Cetuximab
ƒNƒŠƒbƒN‚·‚é‚ƕʃEƒBƒ“ƒhƒE‚ªŠJ‚«‚Ü‚·

EOPUSŽŽŒ±

@OPUSŽŽŒ±i‘æII‘ŠŽŽŒ±j‚Å‚ÍA‰‰ñŽ¡—×á‚ɑ΂·‚éFOLFOX’P“Æ‚ÆCetuximab•¹—p‚ª”äŠr‚³‚ꂽBKRAS–춌^‚Å‚ÍAOS‚É‚¨‚¢‚Ä‚Í—LˆÓ·‚ð”F‚ß‚È‚©‚Á‚½‚à‚Ì‚ÌiFOLFOX{Cetuximab vs. FOLFOX=22.8ƒ•ŒŽ vs. 18.5ƒ•ŒŽ, HR=0.855, p=0.385jAŽå—v•]‰¿€–Ú‚Å‚ ‚é‘tŒø—¦iŠeX57.3% vs. 34.0%, p=0.0027j‚¨‚æ‚ÑPFSiŠeX8.3ƒ•ŒŽ vs. 7.2ƒ•ŒŽ, HR=0.567, p=0.0064j‚É‚¨‚¢‚ÄCetuximab•¹—pŒQ‚ª—LˆÓ‚Éã‰ñ‚Á‚½B
@ ˆê•ûAKRAS•ÏˆÙŒ^‚Å‚Í‘tŒø—¦iŠeX34% vs. 53%, p=0.029jAPFSiŠeX 5.5ƒ•ŒŽ vs. 8.6ƒ•ŒŽ, HR=1.72, p=0.0153jAOSiŠeX13.4ƒ•ŒŽ vs. 17.5ƒ•ŒŽ, HR=1.29, p=0.2004j‚ÆCetuximab•¹—pŒQ‚ª‰º‰ñ‚éŒXŒü‚Å‚ ‚Á‚½42)B

ECOINŽŽŒ±

@‰‰ñŽ¡—Âɂ¨‚¯‚éFOLFOX / XELOX‚ɑ΂·‚éCetuximab‚ÌOS‚É‚¨‚¯‚éã悹‚ðŒŸØ‚µ‚½ŽŽŒ±‚ªCOINŽŽŒ±‚Å‚ ‚éBKRAS–춌^‚É‚¨‚¢‚ÄA‘tŒø—¦‚ÍCetuximab•¹—pŒQ64%A‰»Šw—Ö@’P“ÆŒQ57%ip=0.049j‚ÆCetuximab•¹—p‚É‚æ‚éã悹‚ð”F‚ß‚½‚à‚Ì‚ÌAŽå—v•]‰¿€–Ú‚Å‚ ‚éOS‚ÍŠeX17.0ƒ•ŒŽ vs. 17.9ƒ•ŒŽiHR=1.04, 95% CI: 0.87-1.23, p=0.67j‚ÆACetuximab•¹—p‚É‚æ‚é—D‰z«‚ðŽ¦‚·‚±‚Æ‚ª‚Å‚«‚È‚©‚Á‚½B‚Ü‚½PFS‚É‚¨‚¢‚Ä‚àŠeX8.6ƒ•ŒŽ vs. 8.6ƒ•ŒŽiHR=0.96, 95% CI: 0.82-1.12, p=0.60j‚Æ—LˆÓ·‚ð”F‚ß‚È‚©‚Á‚½69)B‚È‚¨AƒTƒu‰ðÍ‚Å‚ÍKRAS–춌^‚ÌFOLFOX•¹—p‚©‚“]ˆÚ•””1ˆÈ‰º‚ÌÇ—á‚É‚¨‚¢‚Ä‚Ì‚ÝACetuximab‚Ìã悹Œø‰Ê‚ª”F‚ß‚ç‚ꂽiHR=0.55, 95% CI: 0.35-0.87jB

ENORDIC VIIŽŽŒ±

@NORDIC VIIŽŽŒ±‚ÍA–k‰¢‚É‚¨‚¢‚ÄŽg—p‚³‚ê‚Ä‚¢‚éFLOXƒŒƒWƒƒ“‚ðƒx[ƒX‚Æ‚µ‚ÄA‰‰ñŽ¡—Âɂ¨‚¢‚ÄFLOX{CetuximabAFLOXŠÔŒ‡“Š—^{CetuximabˆÛŽ—Ö@AFLOX’P“Æ‚Ì3ŒQ–³ìˆ×‰»”äŠrŽŽŒ±‚Æ‚µ‚Äs‚í‚ꂽBŽå—v•]‰¿€–Ú‚Å‚ ‚éPFS‚ÍAŠeX8.3ƒ•ŒŽ vs. 7.3ƒ•ŒŽ vs. 7.9ƒ•ŒŽ‚Å‚ ‚èAFLOX’P“ÆŒQ‚ÆFLOX{CetuximabŒQ‚Æ‚ÌŠÔ‚É—LˆÓ·‚Í”F‚ß‚ç‚ê‚È‚©‚Á‚½iHR=0.89, p=0.31j70)BKRAS–춌^‚¨‚æ‚ÑKRAS–춌^‚©‚ÂBRAF–춌^‚ÌÇ—á‚É‚¨‚¢‚Ä‚àACetuximab•¹—p‚É‚æ‚éPFS‰„’·Œø‰Ê‚Í”F‚ß‚ç‚ê‚È‚©‚Á‚½Bˆê•ûAKRAS•ÏˆÙŒ^‚É‚¨‚¯‚éPFS‚ÍAFLOX{CetuximabŒQ9.2ƒ•ŒŽAFLOXŒQ7.8ƒ•ŒŽiHR=0.71, p=0.07j‚ÆAFLOX{CetuximabŒQ‚Å—ÇD‚ÈŒXŒü‚ª‚Ý‚ç‚ꂽB‚Ü‚½AOS‚É‚¨‚¢‚Ä‚àAKRAS–춌^AKRAS–춌^‚©‚ÂBRAF–춌^AKRAS•ÏˆÙŒ^‚ÌŠeƒOƒ‹[ƒv‚ÅŽ¡—ÃŒƒWƒƒ“‚É‚æ‚é·‚ð”F‚ß‚È‚©‚Á‚½B

@OPUSŽŽŒ±‚ÌŒ‹‰Ê‚ª•ñ‚³‚ꂽŒãANCCNƒKƒCƒhƒ‰ƒCƒ“‚Å‚ÍKRAS–춌^‚É‚¨‚¯‚鉉ñŽ¡—ÂÌ1‚‚Ƃµ‚ÄFOLFOX{Cetuximab‚ªŒfÚ‚³‚ê‚Ä‚¢‚½‚ªA‚»‚ÌŒã‚Ì2‚‚̑æIII‘ŠŽŽŒ±iCOINANORDIC VIIj‚Ńtƒb‰»ƒsƒŠƒ~ƒWƒ“Œn»Ü{L-OHP•¹—p—Ö@‚ɑ΂·‚éCetuximab‚Ìã悹Œø‰Ê‚ðŽ¦‚·‚±‚Æ‚ª‚Å‚«‚È‚©‚Á‚½‚½‚ßANCCNƒKƒCƒhƒ‰ƒCƒ“‚Ì2011”Nversion 3.2012ˆÈ~AFOLFOX{Cetuximab‚Í휂³‚ꂽB
@‚±‚ê‚ç2‚‚̑æIII‘ŠŽŽŒ±‚ÅCetuximab‚Ì—L—p«‚ðŽ¦‚¹‚È‚©‚Á‚½Œ´ˆö‚Í–¾‚ç‚©‚Å‚Í‚È‚¢‚ªACOINŽŽŒ±‚É‚¨‚¯‚éPFS‚ÉŠÖ‚·‚éƒTƒu‰ðÍ‚É‚¨‚¢‚ÄOPUSŽŽŒ±‚Æ“¯—l‚ÉFOLFOX‚ɑ΂µ‚Ä‚ÍCetuximab‚Ìã悹Œø‰Ê‚ð”F‚ß‚Ä‚¢‚邱‚Æ‚æ‚è69)AXELOX‚É‚¨‚¯‚éCapecitabine‚âFLOX‚É‚¨‚¯‚é5-FU/LV‹}‘¬Ã’‚È‚ÇA•¹—p‚·‚éƒtƒb‰»ƒsƒŠƒ~ƒWƒ“Œn»Ü‚Æ‚Ì‘ŠŒÝì—p‚É–â‘肪‚ ‚Á‚½‰Â”\«‚àŽw“E‚³‚ê‚Ä‚¢‚éB

3.3@Panitumumab

@PanitumumabiƒxƒNƒeƒBƒrƒbƒNƒX®j‚ÍEGFR‚ɑ΂·‚éƒqƒgŒ^IgG2ƒ‚ƒmƒNƒ[ƒiƒ‹R‘Ì‚Å‚ ‚èACetuximab“¯—lEGFR‚ÉŒ‹‡‚·‚邱‚Æ‚É‚æ‚èAŽîᇑB‚¨‚æ‚Ñ“]ˆÚ—}§‚ªŠú‘Ò‚³‚ê‚éBCetuximab‚ªƒLƒƒ‰Œ^‚ÌR‘Ì‚Å‚ ‚èAinfusion reaction—\–h‚Ì‚½‚ß‚ÉRƒqƒXƒ^ƒ~ƒ“–ò‚Ì‘O“Š—^‚ð—v‚·‚é‚̂ɑ΂µAPanitumumab‚ÍŠ®‘SƒqƒgŒ^R‘Ì‚Å‚ ‚邱‚Æ‚©‚çinfusion reaction‚Ì•p“x‚ª­‚È‚­iGrade 3ˆÈã <1%j54)A‘O“Š–ò‚Ì‹K’è‚Í‚È‚¢B‚Ü‚½A“Š–òŠÔŠu‚ÍCetuximab‚ª–ˆT“Š—^‚Å‚ ‚é‚̂ɑ΂µAPanitumumab‚ÍŠuT“Š—^‚Å‚ ‚éB
@–ò•¨—LŠQ”½‰ž‚Æ‚µ‚ÄAinfusion reaction‚Ì‚Ù‚©A”畆áŠQAŠÔŽ¿«”xŽ¾Š³A‰º—Ÿ‚È‚ÇACetuximab‚ÆŠT‚Ë“¯—l‚Ì•ñ‚ª‚È‚³‚ê‚Ä‚¢‚éB

3.3.1@Panitumumab’PÜ Updated
3.3.1 Panitumumab’PÜ
ƒNƒŠƒbƒN‚·‚é‚ƕʃEƒBƒ“ƒhƒE‚ªŠJ‚«‚Ü‚·

E20020408ŽŽŒ±
@5-FUACPT-11AL-OHP‚É•s‰ž‚Æ‚È‚Á‚½Ç—á‚ɑ΂µABSC‚Æ‚Ì”äŠrŽŽŒ±i20020408ŽŽŒ±j‚ªs‚í‚êAŽå—v•]‰¿€–Ú‚Å‚ ‚éPFS‚̉„’·iPanitumumab vs. BSC=8T vs. 7.3T, HR=0.54, p<0.0001j‚ð”F‚ßA‘tŒø—¦‚É‚¨‚¢‚Ä‚à—LˆÓ‚Éã‰ñ‚Á‚½iŠeX10% vs. 0%Ap<0.0001jBOS‚Í—¼ŒQŠÔ‚Å·‚ª‚È‚©‚Á‚½‚ªiHR=1.00, p=0.81jABSCŒQ‚Ì76%‚ÌŠ³ŽÒ‚ª–{ŽŽŒ±‚Æ•Às‚µ‚Äs‚í‚ê‚Ä‚¢‚½Panitumumab’PÜ“Š—^‚Ì‘æII‘ŠŽŽŒ±‚É“o˜^‚³‚êAPanitumumab‚ªŽg—p‚³‚ꂽŒ‹‰Ê‚Æl‚¦‚ç‚ê‚Ä‚¢‚é55)B
@ ‚»‚ÌŒãKRAS•ÏˆÙ‚Ì—L–³‚É‚æ‚é‰ðÍ‚ª‚È‚³‚êABSC‚Æ‚Ì”äŠr‚É‚¨‚¢‚ÄKRAS–춌^‚Å‚Í‘tŒø—¦17%APFSiPanitumumab vs. BSC=12.3T vs. 7.3T, HR=0.45, p<0.0001j‚Åã‰ñ‚Á‚½‚ªAKRAS•ÏˆÙŒ^‚Å‚ÍPFSiPanitumumab vs. BSC=7.4T vs. 7.3T, HR=0.99j‚ÆBSC‚Æ“¯’ö“x‚ÅA‘tŒø—á‚Í”F‚ß‚È‚©‚Á‚½56)B
EASPECCTŽŽŒ±
@20020408ŽŽŒ±‚Å‚ÍBSCŒQ‚Ì76%‚ÅPanitumumab‚ª“Š—^‚³‚ꂽ‚±‚Æ‚©‚çOS‚É—LˆÓ·‚ð”F‚ß‚È‚©‚Á‚½‚½‚ßANCI CTG CO.17ŽŽŒ±‚ÅOS‚É—LˆÓ·‚ð”F‚ß‚½Cetuximab‚ɑ΂µ‚ÄPanitumumab‚Ì”ñ—ò«‚ðŒŸØ‚·‚é‘æIII‘ŠŽŽŒ±AASPECCTŽŽŒ±‚ªs‚í‚ꂽB
@ƒtƒb‰»ƒsƒŠƒ~ƒWƒ“AL-OHPACPT-11‚É•s‰ž‚ÅA‚©‚ÂREGFRR‘Ì–ò‚ÌŽg—p—ð‚Ì‚È‚¢KRAS exon 2–춌^‚ÌÇ—á‚ð‘ÎÛ‚Æ‚µAŽå—v•]‰¿€–Ú‚Å‚ ‚éOS’†‰›’l‚ÍACetuximabŒQ10.0ƒ•ŒŽAPanitumumabŒQ10.4ƒ•ŒŽ‚ÅiHR=0.97, 95% CI: 0.84-1.11, ”ñ—ò«ŒŸ’èp=0.0007, retention rate=1.06jACetuximab‚ɑ΂·‚éPanitumumabŒQ‚Ì”ñ—ò«‚ªŽ¦‚³‚ꂽ84)B‚Ü‚½APFS’†‰›’l‚Í‚»‚ꂼ‚ê4.1ƒ•ŒŽA4.4ƒ•ŒŽiHR=1.002, 95% CI: 0.882-1.138jA‘tŒø—¦‚Í‚»‚ꂼ‚ê22.0%A19.8%‚Å‚ ‚èA—¼ŒQŠÔ‚É·‚ð”F‚ß‚È‚©‚Á‚½B‚È‚¨AŒãŽ¡—Â̎{s—¦‚â‚»‚Ì“à—e‚à—ÞŽ—‚µ‚Ä‚¢‚½B
@Žå‚È—LŠQŽ–Û‚Í—¼ŒQ‚ÅŠT‚Ë“¯’ö“x‚Å‚ ‚Á‚½‚ªA’áƒ}ƒOƒlƒVƒEƒ€ŒŒÇ‚ÍPanitumumabŒQ28.8%ACetuximabŒQ18.9%‚ÆPanitumumabŒQ‚Å‘½‚­Ainfusion reaction‚Í‚»‚ꂼ‚ê2.8%A12.5%‚ÆCetuximabŒQ‚Å‘½‚¢ŒXŒü‚É‚ ‚Á‚½B
@ˆÈã‚æ‚èAƒtƒb‰»ƒsƒŠƒ~ƒWƒ“AL-OHPACPT-11‚É‚æ‚鎡—×ð‚Ì‚ ‚éKRAS exon 2–춌^‚É‚¨‚¯‚éPanitumumab’PÜ‚ÍACetuximab’PÜ‚Æ“¯’ö“x‚ÌRŽîᇌø‰Ê‚ð—L‚µA“Å«ƒvƒƒtƒ@ƒCƒ‹‚à—ÞŽ—‚µ‚Ä‚¢‚½B

3.3.2@FOLFOX{Panitumumab Updated
3.3.2 FOLFOX{Panitumumab
ƒNƒŠƒbƒN‚·‚é‚ƕʃEƒBƒ“ƒhƒE‚ªŠJ‚«‚Ü‚·

EPRIMEŽŽŒ±
@PRIMEŽŽŒ±‚Å‚ÍA‰‰ñŽ¡—×á‚É‚¨‚¯‚éFOLFOX‚ɑ΂·‚éPanitumumab‚Ìã悹Œø‰Ê‚ªŒŸ“¢‚³‚ꂽB
@ KRAS–춌^‚É‚¨‚¢‚ÄA‘tŒø—¦iFOLFOX{Panitumumab vs. FOLFOX=55% vs. 48%, p=0.07jAOSiŠeX23.9ƒ•ŒŽ vs. 19.7ƒ•ŒŽ, HR=0.83, p=0.07j‚Å‚Í—LˆÓ·‚ð”F‚ß‚È‚©‚Á‚½‚à‚Ì‚ÌPanitumumab•¹—pŒQ‚Å—ÇD‚ÈŒXŒü‚É‚ ‚èAŽå—v•]‰¿€–Ú‚Å‚ ‚éPFS‚ÍAPanitumumab•¹—pŒQ‚Å—LˆÓ‚ÉFOLFOX’P“ÆŒQ‚ðã‰ñ‚Á‚½iŠeX 9.6ƒ•ŒŽ vs. 8.0ƒ•ŒŽ, HR=0.80, p=0.02jB
@ˆê•ûAKRAS•ÏˆÙŒ^‚Å‚ÍPFSiŠeX7.3ƒ•ŒŽ vs. 8.8ƒ•ŒŽ, HR=1.29, p=0.02jAOSiŠeX15.5ƒ•ŒŽ vs. 19.3ƒ•ŒŽ, HR=1.24, p=0.07jA‘tŒø—¦iŠeX40% vs. 40%, p=0.98j‚ÆAPanitumumab•¹—pŒQ‚ª‰º‰ñ‚éŒXŒü‚É‚ ‚Á‚½43)B‚±‚ÌŒ‹‰Ê‚©‚çAKRAS–춌^‚̈ꎟŽ¡—Âɂ¨‚¯‚éPanitumumab‚Ì—LŒø«‚ªŽ¦‚³‚ꂽB
@‚È‚¨A2011”N•Ä‘—Õ°Žîᇊw‰ï”NŽŸW‰ï‚É‚ÄPRIMEŽŽŒ±‚ÌÅI•ñ‚Æ‚µ‚Ä“o˜^I—¹30ƒ•ŒŽŒã‚É‚¨‚¯‚é‰ðÍŒ‹‰Ê‚ª•ñ‚³‚ꂽBPFS‚ÍFOLFOX{PanitumumabŒQ10.0ƒ•ŒŽAFOLFOXŒQ8.6ƒ•ŒŽiHR=0.80, 95% CI: 0.67-0.95, p=0.01jA‘tŒø—¦‚ÍŠeX57% vs. 48%ip=0.02j‚ÆPanitumumab•¹—pŒQ‚ª—LˆÓ‚É—ÇD‚Å‚ ‚Á‚½‚ªAOS‚ɂ‚¢‚Ă͉‰ñ•ñ‚Æ“¯—lAŠeX23.9ƒ•ŒŽ vs. 19.7ƒ•ŒŽiHR=0.88, 95% CI: 0.73-1.06, p=0.17j‚ÆAPanitumumab•¹—pŒQ‚Å—ÇD‚ÈŒXŒü‚Å‚ ‚é‚à‚Ì‚Ì—LˆÓ·‚Í”F‚ß‚È‚©‚Á‚½71)B‚Ü‚½AKRAS•ÏˆÙŒ^‚É‚¨‚¢‚Ä‚à‰‰ñ•ñ‚Æ“¯—lAPanitumumab•¹—pŒQ‚ÅPFS‚Í‚Æ‚à‚ɉº‰ñ‚éŒXŒü‚É‚ ‚Á‚½iHR=1.27, 95% CI: 1.04-1.55, p=0.02jAOS‚à’Z‚¢ŒXŒü‚É‚ ‚Á‚½iHR=1.17, 95% CI: 0.95-1.45, p=0.15jB
@2013”N•Ä‘—Õ°Žîᇊw‰ï”NŽŸW‰ï‚Å‚ÍA’Tõ“I‰ðÍ‚Æ‚µ‚ăCƒxƒ“ƒg”­¶—¦82%Žž“_‚É‚¨‚¯‚éOS‰ðÍ‚ª•ñ‚³‚ꂽBKRAS exon 2–춌^‚É‚¨‚¯‚éOS’†‰›’l‚ÍFOLFOX4ŒQ19.4ƒ•ŒŽAPanitumumab•¹—pŒQ23.8ƒ•ŒŽ‚Å‚ ‚èAPanitumumab•¹—pŒQ‚ª—LˆÓ‚Éã‰ñ‚Á‚½iHR=0.83, 95% CI: 0.70-0.98, p=0.027j85)Bˆê•ûKRAS exon 2•ÏˆÙŒ^‚É‚¨‚¢‚Ä‚Í‘O‰ñ‚Ì•ñ‚Æ“¯—lAPanitumumab•¹—pŒQ‚ª‰º‰ñ‚éŒXŒü‚É‚ ‚Á‚½iHR=1.16, 95% CI: 0.94-1.41, p=0.162jB
@‚Ü‚½AŽ–‘O‚ÉŒv‰æ‚³‚ê‚Ä‚¢‚½’Tõ“IƒoƒCƒIƒ}[ƒJ[Œ¤‹†‚Æ‚µ‚ÄAKRAS exon 3, 4ANRAS exon 2, 3, 4•ÏˆÙ‚Ì—L–³‚É‚æ‚éRAS‰ðÍ‚ª•ñ‚³‚êAÅV‚ÌOS‰ðÍŽž“_‚É‚¨‚¯‚éRAS‰ðÍ‚ÌŒ‹‰Ê‚àESMO 2013‚Å•ñ‚³‚ꂽB‚±‚ê‚çRASˆâ“`Žq‚̕ψقÍ90%‚ÌÇ—á‚ʼnð͉”\‚Å‚ ‚èAKRAS exon 2–춌^‚Ì‚¤‚¿17%‚É‘¼‚Ì‚¢‚¸‚ê‚©‚ÌRAS•ÏˆÙ‚ð”F‚ß‚½86)B‘S‚Ä‚ÌRAS‚ɕψقð”F‚ß‚È‚¢RAS–춌^‚É‚¨‚¯‚éPFS‚ÌHR=0.72iKRAS exon 2–춌^‚ÌHR=0.80jAOS‚ÌHR=0.77iKRAS exon 2–춌^‚ÌHR=0.83j87)‚Å‚ ‚èARAS–춌^‚ÅPanitumumab•¹—p‚ÌŒø‰Ê‚ª‚æ‚è‚‚¢‚±‚Æ‚ªŽ¦‚³‚ꂽBˆê•ûA‚¢‚¸‚ê‚©‚ÌRAS•ÏˆÙ‚ð—L‚·‚銳ŽÒŒQ‚É‚¨‚¢‚Ä‚ÍAPFS‚ÌHR=1.31ip=0.008j86)AOS‚ÌHR=1.21ip=0.040j87)‚ÅA—LˆÓ‚ÉPanitumumab•¹—pŒQ‚ª—ò‚Á‚Ä‚¢‚½B
@‚±‚ÌRAS‰ðÍ‚É‚æ‚錟“¢‚É‚¨‚¢‚ÄAPanitumumab‚ÍRAS–ì«Œ^‚Å‚Ì‚Ý‚»‚ÌŒø‰Ê‚ð‹Žó‚Å‚«‚邱‚Æ‚ªŽ¦‚³‚ꂽBPanitumumab‚ÌŽg—p‚É‚¨‚¢‚Ä‚Í‘S‚Ä‚ÌRASŒŸ¸‚ª‹‚ß‚ç‚ê‚é‚Æl‚¦‚ç‚ê‚éB
EPEAKŽŽŒ±
@PEAKŽŽŒ±‚ÍAKRAS exon 2–춌^‚̉‰ñŽ¡—×á‚É‚¨‚¢‚ÄAFOLFOX{Panitumumab‚ÆFOLFOX{Bevacizumab‚ð”äŠr‚µ‚½–³ìˆ×‰»‘æII‘ŠŽŽŒ±‚Å‚ ‚éB‰‰ñ•ñ‚Å‚ÍPanitumumabŒQ142—áABevacizumabŒQ143—ႪITT‰ðÍ‚Ì‘ÎÛ‚Å‚ ‚èAŽå—v•]‰¿€–Ú‚Å‚ ‚éPFS‚ÍPanitumumabŒQ10.9ƒ•ŒŽABevacizumabŒQ10.1ƒ•ŒŽ‚ÅA—¼ŒQŠÔ‚É—LˆÓ·‚ð”F‚ß‚È‚©‚Á‚½iHR=0.87, 95% CI: 0.65-1.17, p=0.35j88)B‚Ü‚½A‘tŒø—¦‚Í‚»‚ꂼ‚ê58%A54%A—LŠQŽ–Û‚É‚æ‚鎡—Ã’†Ž~‚Í‚»‚ꂼ‚ê24%A27%‚ÆA‚¢‚¸‚ê‚à—¼ŒQ‚Å“¯“™‚Å‚ ‚Á‚½Bˆê•ûOS‚ÍAPanitumumabŒQ‚Å‚Í’†‰›’l–¢“ž’BABevacizumabŒQ25.4ƒ•ŒŽ‚Å‚ ‚èA—LˆÓ·‚Í‚È‚¢‚à‚Ì‚ÌPanitumumabŒQ‚Å—ÇD‚ÈŒXŒü‚Å‚ ‚Á‚½iHR=0.72, 95% CI: 0.47-1.11, p=0.14jB
@‚»‚ÌŒãAŽ–‘O‚ÉŒv‰æ‚³‚ê‚Ä‚¢‚½KRAS exon 3, 4ANRAS exon 2, 3, 4ABRAF exon 15‚É‚æ‚é’ljÁ‰ðÍ‚¨‚æ‚ÑOS‚Ìupdate‚ª•ñ‚³‚ꂽBITT‰ðÍW’c‚Ì80%‚ňâ“`Žq‰ðÍ‚ªs‚í‚êAPanitumumabŒQ88—áABevacizumabŒQ82—ႪAKRASANRAS‚Ì‚¢‚¸‚ê‚̕ψقà—L‚³‚È‚¢RAS–춌^‚Æ‚µ‚ĒljÁ‰ðÍ‘ÎÛ‚Æ‚È‚Á‚½BRAS–춌^‚É‚¨‚¯‚éPFS’†‰›’l‚ÍAPanitumumabŒQ13.0ƒ•ŒŽABevacizumabŒQ10.1ƒ•ŒŽ‚ÅAPanitumumabŒQ‚Å—LˆÓ‚ȉ„’·‚ð”F‚ß‚½iHR=0.66, 95% CI: 0.46-0.95, p=0.03j89)B‚Ü‚½AOS’†‰›’l‚à‚»‚ꂼ‚ê41.3ƒ•ŒŽA28.9ƒ•ŒŽ‚ÆAPanitumumabŒQ‚Å—ÇD‚ÈŒXŒü‚Å‚ ‚Á‚½iHR=0.63, 95% CI: 0.39-1.02, p=0.06jB‚È‚¨A2nd-line‚É‚¨‚¯‚éPanitumumabŒQ‚ÌRVEGF»Ü‚É‚æ‚鎡—צABevacizumabŒQ‚ÌREGFRR‘Ì–ò‚É‚æ‚鎡—צ‚ÍA‚Æ‚à‚É40%’ö“x‚Å‚ ‚Á‚½B
@ˆÈãA–{ŽŽŒ±‚ÍŽ–‘O‚̉¼àݒ肪‚È‚©‚Á‚½‚±‚Æ‚ªŽw“E‚³‚ê‚é‚à‚Ì‚ÌA‰‰ñŽ¡—ÂƂµ‚Ä‚ÌFOLFOX{Panitumumab‚ÍA‘ÎÛ‚ðRAS–춌^‚ÉŒÀ’è‚·‚邱‚Æ‚ÅAFOLFOX{Bevacizumab‚æ‚è‚à—LŒø‚Å‚ ‚é‰Â”\«‚ªŽ¦´‚³‚ꂽB

3.3.3@FOLFIRI{Panitumumab Updated
3.3.3 FOLFIRI{Panitumumab
ƒNƒŠƒbƒN‚·‚é‚ƕʃEƒBƒ“ƒhƒE‚ªŠJ‚«‚Ü‚·

E20050181ŽŽŒ±
@20050181ŽŽŒ±‚Å‚ÍA“ñŽŸŽ¡—×á‚É‚¨‚¯‚éFOLFIRI‚ɑ΂·‚éPanitumumab‚Ìã悹Œø‰Ê‚ªŒŸ“¢‚³‚ꂽB
@ KRAS–춌^‚Å‚ÍAOS‚É‚¨‚¢‚Ä‚Í—LˆÓ·‚ð”F‚ß‚È‚©‚Á‚½‚à‚Ì‚ÌiFOLFIRI{Panitumumab vs. FOLFIRI=14.5ƒ•ŒŽ vs. 12.5ƒ•ŒŽ, HR=0.85, p=0.12jAŽå—v•]‰¿€–Ú‚Ì1‚‚ł ‚éPFSiŠeX5.9ƒ•ŒŽ vs. 3.9ƒ•ŒŽ, HR=0.73, p=0.004j‚¨‚æ‚Ñ‘tŒø—¦iŠeX35% vs. 10%, p<0.001j‚É‚¨‚¢‚ÄAPanitumumab•¹—pŒQ‚ª—LˆÓ‚ÉFOLFIRI’P“ÆŒQ‚ðã‰ñ‚Á‚½Bˆê•ûAKRAS•ÏˆÙŒ^‚Å‚ÍAPFSAOSA‘tŒø—¦‚Ì‚¢‚¸‚ê‚É‚¨‚¢‚Ä‚àAPanitumumab•¹—p‚É‚æ‚éŒø‰Ê‚Ìã悹‚Í”F‚ß‚ç‚ê‚È‚©‚Á‚½57)B
@ –{Œ‹‰Ê‚æ‚èAKRAS–춌^‚Ì“ñŽŸŽ¡—Âɂ¨‚¯‚éPanitumumab‚Ì—LŒø«‚ªŽ¦‚³‚ꂽB
@‚È‚¨A2012”N•Ä‘—Õ°Žîᇊw‰ï”NŽŸW‰ï‚É‚¨‚¢‚Ä–{ŽŽŒ±‚ÌÅI“o˜^30ƒ•ŒŽŒã‚̉ðÍ‚ª•ñ‚³‚ꂽBKRAS–춌^‚É‚¨‚¯‚éPFS‚ÍFOLFIRI{PanitumumabŒQ6.7ƒ•ŒŽAFOLFIRI’P“ÆŒQ4.9ƒ•ŒŽiHR=0.82, 95% CI: 0.69-0.97, p=0.023jA‘tŒø—¦‚ÍŠeX36.0% vs. 9.8%iƒIƒbƒY”ä5.50, 95% CI: 3.32-8.87, p<0.0001j‚ÆAPanitumumab•¹—pŒQ‚ª—LˆÓ‚Éã‰ñ‚Á‚½72)BOS‚ÍŠeX14.5ƒ•ŒŽ vs. 12.5ƒ•ŒŽiHR=0.92, 95% CI: 0.78-1.10, p=0.366j‚ÆPanitumumab•¹—pŒQ‚Å’·‚¢ŒXŒü‚É‚ ‚Á‚½‚à‚Ì‚Ì—LˆÓ·‚Í”F‚ß‚ç‚ê‚È‚©‚Á‚½BGrade 3/4‚Ì—LŠQŽ–ۂɂ‚¢‚Ä‚à”畆áŠQ iŠeX37% vs. 2%j‚≺—ŸiŠeX14% vs. 9%j“™APanitumumab•¹—pŒQ‚Å‘½‚­”F‚ß‚ç‚ꂽ‚ªA’·ŠúŠÏŽ@‚É‚æ‚é–¾‚ç‚©‚È—LŠQŽ–Û‚Ì‘‰Á‚Í”F‚ß‚È‚©‚Á‚½B‚Ü‚½AKRAS•ÏˆÙŒ^‚É‚¨‚¢‚Ä‚ÍOSAPFSA‘tŒø—¦‚Æ‚à“¯’ö“x‚Å‚ ‚Á‚½B
ESPIRITTŽŽŒ±
@SPIRITTŽŽŒ±‚ÍAKRAS exon 2–춌^‚ÅBevacizumab‚ÆL-OHPƒx[ƒX‚Ì•¹—p—Ö@‚É•s‰ž‚Æ‚È‚Á‚½Ç—á‚ð‘ÎÛ‚ÉA2nd-line‚É‚¨‚¢‚ÄFOLFIRI{Panitumumab‚ÆFOLFIRI{Bevacizumab‚ð”äŠr‚µ‚½–³ìˆ×‰»‘æII‘ŠŽŽŒ±‚Å‚ ‚éBŽå—v•]‰¿€–Ú‚Å‚ ‚éPFS’†‰›’l‚ÍAPanitumumabŒQ7.7ƒ•ŒŽABevacizumabŒQ9.2ƒ•ŒŽiHR=1.01, 95% CI: 0.68-1.50jAOS’†‰›’l‚Í‚»‚ꂼ‚ê18.0ƒ•ŒŽA21.4ƒ•ŒŽ‚ÅiHR=1.06, 95% CI: 0.75-1.49jA‚Æ‚à‚É—¼ŒQŠÔ‚É—LˆÓ·‚ð”F‚ß‚È‚©‚Á‚½90)B‚È‚¨A‘tŒø—¦‚Í‚»‚ꂼ‚ê32%A19%‚ÆAPanitumumabŒQ‚Å—ÇD‚Å‚ ‚Á‚½B
@Grade 3/4‚Ì—LŠQŽ–Û‚ÍPanitumumabŒQ78%ABevacizumabŒQ65%‚É”F‚ßA—LŠQŽ–Û‚É‚æ‚鎡—Ã’†Ž~‚ÍA‚»‚ꂼ‚ê29%A25“‚Æ—¼ŒQ‚Å“¯’ö“x‚Å‚ ‚Á‚½BREGFRR‘Ì–ò‚É‚æ‚éŒãŽ¡—ÂÍAPanitumumabŒQ26%ABevacizumabŒQ54%ARVEGF»Ü‚É‚æ‚éŒãŽ¡—Â͂»‚ꂼ‚ê20%A24%‚Å‚ ‚Á‚½B
@PEAKŽŽŒ±“¯—lA–{ŽŽŒ±‚͉¼àÝ’è‚Ì‚È‚¢ŽŽŒ±‚Å‚ ‚Á‚½‚ªAL-OHP‚¨‚æ‚ÑBevacizumab•s‰ž‚ÌKRAS exon 2–춌^‚É‚¨‚¢‚ÄAFOLFIRI + Panitumumab‚ÆFOLFIRI + Bevacizumab‚ÌOS‚Í“¯’ö“x‚Å‚ ‚Á‚½B

3.3.4@CPT-11{Panitumumab
3.1.3 IFL{Bevacizumab
ƒNƒŠƒbƒN‚·‚é‚ƕʃEƒBƒ“ƒhƒE‚ªŠJ‚«‚Ü‚·

EGERCORŽŽŒ±

@GERCORŽŽŒ±‚̓tƒb‰»ƒsƒŠƒ~ƒWƒ“Œn»ÜAL-OHPACPT-11‚É•s‰ž‚Æ‚È‚Á‚½KRAS–춌^‚É‚¨‚¯‚éCPT-11i180mg/m2j{Panitumumabi6mg/kgj‚Ì—LŒø«‚ðŒŸ“¢‚µ‚½’PƒA[ƒ€‘æII‘ŠŽŽŒ±‚Å‚ ‚éBŽå—v•]‰¿€–Ú‚Í‘tŒø—¦‚ÅAŠú‘Ò’l‚ð30%‚Éݒ肵‚½B’†‰›”»’è‚É‚æ‚éKRASˆâ“`ŽqŒŸ¸‚ɂĕψقð”F‚ß‚È‚©‚Á‚½61—Ⴊ‰ðÍ‘ÎÛ‚Æ‚È‚èA‘tŒø—¦‚Í32.8%i20/61—ájA•a¨ƒRƒ“ƒgƒ[ƒ‹—¦‚Í68.9%i42/61—áj‚Å‚ ‚Á‚½73)BŠÏŽ@ŠúŠÔ’†‰›’l16.8ƒ•ŒŽ‚ÌŽž“_‚ÅAPFS‚Í6.0ƒ•ŒŽi95% CI: 4.6-7.9jAOS‚Í14.5ƒ•ŒŽi95% CI: 6.8-18.2j‚Å‚ ‚Á‚½B
@CPT-11•s‰ž—á‚ɑ΂·‚éREGFRR‘Ì–ò‚ÆCPT-11‚Ì•¹—p‚ɂ‚¢‚Ä‚ÍAæ‚ÉBONDŽŽŒ±‚ÅCetuximab•¹—p‚É‚æ‚éPFS‚̉„’·Œø‰Ê‚ªŽ¦‚³‚ê‚Ä‚¢‚½‚ª52)APanitumumab‚ɂ‚¢‚Ä‚à“¯—l‚ÈŒ‹‰Ê‚ªŽ¦´‚³‚ꂽB

EPICCOLOŽŽŒ±

@PICCOLOŽŽŒ±‚ÍAƒtƒb‰»ƒsƒŠƒ~ƒWƒ“Œn»Ü‚É‚æ‚鎡—Ã—ð‚ª‚ ‚èACPT-11Žg—p—ð‚Ì‚È‚¢Ç—á‚ð‘ÎÛ‚ÉACPT-11{PanitumumabACPT-11{CiclosporinACPT-11’P“Æ‚Ì3ŒQ‚ð”äŠr‚µ‚½‘æIII‘ŠŽŽŒ±‚Å‚ ‚éB2008”N6ŒŽ‚ɃvƒƒgƒR[ƒ‹‚ª‰ü’ù‚³‚êAKRAS–춌^‚É‚¨‚¯‚éCPT-11’P“Æ‚ÆCPT-11{Panitumumab‚ð”äŠr‚·‚éÝ’è‚É•ÏX‚Æ‚È‚Á‚½B
@KRAS–춌^460—Ⴊ“o˜^‚³‚êAŽå—v•]‰¿€–Ú‚Å‚ ‚éOS‚ÍCPT-11{PanitumumabŒQ10.4ƒ•ŒŽACPT-11’P“ÆŒQ10.5ƒ•ŒŽ‚Å‚ ‚èA—LˆÓ·‚ð”F‚ß‚È‚©‚Á‚½iHR=0.91, 95% CI: 0.73-1.14, p=0.44j74)B•›ŽŸ“I•]‰¿€–Ú‚Å‚ ‚éPFS‚ÍAŠeX5.5ƒ•ŒŽ vs. 4.7ƒ•ŒŽiHR=0.78, 95% CI: 0.64-0.95, p=0.01jA‘tŒø—¦‚ÍŠeX34% vs. 12%ip<0.0001j‚ÆA‚¢‚¸‚ê‚àPanitumumab•¹—pŒQ‚Å—LˆÓ‚É—ÇD‚Å‚ ‚Á‚½B
@‚Ü‚½A–{ŽŽŒ±‚Å‚Í‚ ‚ç‚©‚¶‚ßKRASˆÈŠO‚ÌBRAFAPIK3CAANRASˆâ“`Žq‚̉ðÍ‚ª—\’肳‚ê‚Ä‚¢‚½B‚·‚ׂĂ̈â“`Žq‚ª–춌^‚ÌÇ—á‚É‚¨‚¢‚ÄPanitumumab•¹—p‚ÍPFS‚̉„’·‚ðŽ¦‚µ‚½‚ªiHR=0.70, p=0.01jAOS‚Å‚Í—LˆÓ·‚ð”F‚ß‚È‚©‚Á‚½iHR=0.86, p=0.32jBˆê•ûA‚¢‚¸‚ê‚©‚̈â“`Žq‚ɕψقð—L‚µ‚Ä‚¢‚éÇ—á‚Å‚ÍCPT-11’P“ÆŒQ‚ÅOS‚ª—LˆÓ‚É—ÇD‚Å‚ ‚èiHR=2.03, p<0.01jAŠù•ñ‚Æ“¯—l‚ÉBRAFAPIK3CAANRASˆâ“`Žq‚àPanitumumabŽg—p‚É‚¨‚¯‚éƒoƒCƒIƒ}[ƒJ[‚Æ‚È‚é‰Â”\«‚ªŽ¦´‚³‚ꂽB

3.4@Aflibercept

@Aflibercept‚Í2Ží‚ÌVEGFŽó—e‘ÌiVEGFR-1AVEGFR-2j‚Ì×–EŠOƒhƒƒCƒ“‚̈ꕔ‚ðƒqƒg–ƉuƒOƒƒuƒŠƒ“G1iIgG1j‚ÌFc—̈æ‚É—Z‡‚³‚¹‚½‘gŠ·‚¦—Z‡’`”’Ž¿‚Å‚ ‚éBì—p‹@˜‚Æ‚µ‚Ä‚ÍAVEGFŽó—e‘̃ŠƒKƒ“ƒh‚Å‚ ‚éVEGF-AAVEGF-B‚¨‚æ‚Ñ‘Ù”Õ‘BˆöŽqiPlGFj‚ÉŒ‹‡‚µ‚ÄŽîᇂɂ¨‚¯‚錌ŠÇV¶‚ÆŒŒŠÇ“§‰ß«‚ð‘jŠQ‚·‚邱‚Æ‚ªl‚¦‚ç‚ê‚Ä‚¢‚éB

3.4.1@FOLFIRI{Aflibercept

@VELOURŽŽŒ±‚Å‚ÍAL-OHPƒx[ƒX‚̉‰ñŽ¡—Âɕs‰ž‚Æ‚È‚Á‚½Ç—á‚ð‘ÎÛ‚ÉAFOLFIRI‚ɑ΂·‚éAflibercept‚Ìã悹Œø‰Ê‚ªŒŸ“¢‚³‚ꂽBŽå—v•]‰¿€–Ú‚ÌOS‚ÍFOLFIRI{AfliberceptŒQ13.5ƒ•ŒŽAFOLFIRI’P“ÆŒQ12.1ƒ–ŒŽiHR=0.82, 95.34% CI: 0.71-0.94, p=0.0032jA•›ŽŸ•]‰¿€–Ú‚ÌPFS‚ÍŠeX6.9ƒ•ŒŽ vs. 4.7ƒ•ŒŽiHR=0.76, 99.99% CI: 0.58-1.10, p=0.00007jA‘tŒø—¦‚ÍŠeX19.8% vs. 11.1%ip=0.0001j‚Æ‚¢‚¸‚ê‚àAflibercept‚É‚æ‚éã悹Œø‰Ê‚ª”F‚ß‚ç‚ꂽ75)B
@ˆÈã‚ÌŒ‹‰Ê‚æ‚èA2012”N8ŒŽ‚É•Ä‘FDA‚ų”F‚³‚êANCCNƒKƒCƒhƒ‰ƒCƒ“i2013”N”Åversion1j‚É‚¨‚¢‚Ä‚à„§‚³‚ê‚鎡—Ö@‚Ì1‚‚Ƃµ‚ÄŒfÚ‚³‚ê‚Ä‚¢‚éi2012”N12ŒŽŽž“_‚Å–{–M–¢³”Fj67)B
@‚Ü‚½AŽ–‘O‚É—\’肳‚ê‚Ä‚¢‚½‘OŽ¡—Âɂ¨‚¯‚éBevacizumab“Š—^‚Ì—L–³‚É‚æ‚éAflibercept‚ÌŒø‰Ê‚ɂ‚¢‚Ä‚à‰ðÍ‚ªs‚í‚êABevacizumabŽg—p—ð‚Ì‚ ‚éÇ—á‚É‚¨‚¯‚éOS‚ÍŠeX12.5ƒ•ŒŽ vs. 11.7ƒ•ŒŽiHR=0.862, 95.34% CI: 0.673-1.104jABevacizumabŽg—p—ð‚Ì‚È‚¢Ç—á‚É‚¨‚¢‚Ä‚ÍAŠeX13.9ƒ•ŒŽ vs. 12.4ƒ•ŒŽiHR=0.788, 95.34% CI: 0.699-0.927j‚Å‚ ‚èABevacizumab“Š—^—ð‚Ì—L–³‚É‚æ‚éŒðŒÝì—p‚Í”F‚ß‚È‚©‚Á‚½ip=0.57jB
@Grade 3/4‚Ì—LŠQŽ–ۂ͉º—ŸAŒ‘‘ÓŠ´AŒû“à‰ŠAŠ´õA‚ŒŒˆ³A• ’ÉAD’†‹…Œ¸­A’`”’”A‚ªAflibercept•¹—pŒQ‚Å‘½‚­”F‚ß‚ç‚êA—LŠQŽ–Û‚É”º‚¤Ž¡—Ã’†Ž~—á‚ÍAflibercept•¹—pŒQ‚Å26.6%AFOLFIRI’P“ÆŒQ‚Å12.1%‚ÆAflibercept•¹—pŒQ‚Å‘½‚¢ŒXŒü‚É‚ ‚Á‚½B

3.5@Regorafenib

@Regorafenib‚ÍŽîᇂ̑BE¶‘¶AŒŒŠÇV¶‚ÉŠÖ—^‚·‚éVEGFRAKITARETAFGFRAPDGFR‚È‚Ç‚ð•W“I‚Æ‚·‚éŒoŒûƒ}ƒ‹ƒ`ƒLƒi[ƒ[‘jŠQÜ‚Å‚ ‚éB

3.5.1@Regorafenib’PÜ Updated
3.5.1@Regorafenib’PÜ
ƒNƒŠƒbƒN‚·‚é‚ƕʃEƒBƒ“ƒhƒE‚ªŠJ‚«‚Ü‚·

@CORRECTŽŽŒ±‚Å‚ÍA•W€‰»Šw—Ö@A‚·‚È‚í‚¿ƒtƒb‰»ƒsƒŠƒ~ƒWƒ“Œn»ÜAL-OHPACPT-11ABevacizumabAKRAS–춌^‚É‚¨‚¯‚éREGFRR‘Ì–ò‚É•s‰ž‚Æ‚È‚Á‚½Ç—á‚ð‘ÎÛ‚ÉARegorafenib‚Ì—L—p«‚ªŒŸ“¢‚³‚ꂽBŽå—v•]‰¿€–Ú‚Å‚ ‚éOS‚ÍAŽ–‘O‚É‹K’肳‚ꂽ’†ŠÔ‰ðÍ‚ÌŽž“_‚ÅARegorafenibŒQ6.4ƒ•ŒŽAplaceboŒQ5.0ƒ•ŒŽiHR=0.77, 95% CI: 0.64-0.94, p=0.0052j‚ÆRegorafenibŒQ‚ª—LˆÓ‚Éã‰ñ‚èA—LŒø’†Ž~‚Æ‚È‚Á‚½76)B•›ŽŸ“I•]‰¿€–Ú‚Å‚ ‚éPFS‚É‚¨‚¢‚Ä‚àŠeX1.9ƒ•ŒŽ vs. 1.7ƒ•ŒŽiHR=0.525, 95% CI: 0.42-0.58, p<0.000001j‚ÆRegorafenibŒQ‚Å—LˆÓ‚É—ÇD‚Å‚ ‚Á‚½B—LŠQŽ–Û‚ÍARegorafenibŒQ‚Ågrade 3ˆÈã‚̔畆áŠQAŠÌ‹@”\áŠQA”æ˜J“™‚ª‘½‚­”F‚ß‚ç‚ꂽB
@‚Ü‚½AKRAS•ÏˆÙ‚Ì—L–³‚É‚æ‚éƒTƒuƒOƒ‹[ƒv‰ðÍ‚à•ñ‚³‚êAKRAS–춌^‚É‚¨‚¯‚éOS‚ÍŠeX7.3ƒ•ŒŽ vs. 5.0ƒ•ŒŽiHR=0.653, 95% CI: 0.476-0.895jAKRAS•ÏˆÙŒ^‚É‚¨‚¯‚éOS‚ÍŠeX6.2ƒ•ŒŽ vs. 5.1ƒ•ŒŽiHR=0.867, 95% CI: 0.670-1.123j‚ÆKRAS•ÏˆÙ‚Ì—L–³‚É‚©‚©‚í‚炸RegorafenibŒQ‚Å—ÇD‚Å‚ ‚Á‚½B
@ˆÈã‚ÌŒ‹‰Ê‚æ‚èA2012”N9ŒŽ‚É•Ä‘FDA‚ų”FBNCCNƒKƒCƒhƒ‰ƒCƒ“i2013”N”Åversion1j‚É‚¨‚¢‚Ä‚à„§‚³‚ê‚鎡—Ö@‚Ì1‚‚Ƃµ‚ÄŒfÚ‚³‚ꂽ67)B‚Ü‚½A–{–M‚Å‚à2013”N3ŒŽ25“ú‚ɳ”F‚ðŽæ“¾‚µ‚½B
@‚È‚¨AESMO 2012‚łͶ‘¶ŠúŠÔ‚Ìup date‚ª•ñ‚³‚êA‚»‚ꂼ‚ê‚ÌŽŽŒ±ŒQ‚ÌOS‚Í6.4ƒ•ŒŽ vs. 5.0ƒ•ŒŽiHR=0.79, 95% CI: 0.66-0.94, p=0.0038) ‚ÆA2012”N•Ä‘—Õ°Žîᇊw‰ï”NŽŸW‰ï‚Å‚Ì’†ŠÔ•ñ‚Æ“¯—l‚ÌŒ‹‰Ê‚Å‚ ‚Á‚½77jB

Combination therapy –ÚŽŸ‚Ö Øœ•s”\isÄ”­‘å’°Šà‚ɑ΂·‚鉻Šw—Ö@‚Ì•Ï‘J‚ÆŽ¡—Õûj
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