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Potential Predictive Value of TP53 and KRAS Mutation Status for Response to PD-1 Blockade Immunotherapy in Lung Adenocarcinoma

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PD-L1 expression¹ïanti-PD 1ªºÃĪ«¦³¦h­«­n¡H²{¦bªº¶i«×¨ì¨º¸Ì¡HÁÙ­n§JªAªº¬O¤°»ò¡H

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¡´Àù²Ó­M¤Wªº±µ¦XÅé¡]ligand) PD-L1/PD-L2¥i¥H©MT²Ó­M¤WªºPD-1µ²¦X¦ÓÁקK¾D¨ìT²Ó­MªººR·´¡A©Ò¥H·í

PD-L1 »P PD-1 µ²¦X«á¡A´N·|§í¨î§K¬Ì¨t²Î T ²Ó­Mªº¬¡¤Æ¤Î¼W¥Í¡C

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Keynote001(ªø¦¿¤@¸¹)------ClinicalTrials.gov no. NCT01295827

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Training group=182¡÷171¦³±µ¨ü¹L¨ä¥LªvÀø, 11­Ó¨S¦³¡÷Á`¦@¦³129­Ó¦³¤ÀªRPD-L1 expression

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Response°»´ú=every 9 wks (½Ö¨Ó´ú¡H¡÷central review= central read)

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Fatigue¡÷Any grade= 96(19.4%); Grade 3-5=4(0.8%)

Pruritus¡÷Any grade= 53(10.7%); Grade 3-5=0

Decreased appetite¡÷ Any grade= 52(10.5%); Grade 3-5=5(1%)

ORR= 19.4% (RECIST 1.1)---394¦³±µ¨ü¹L¨ä¥LªvÀøªº¯f¤HORR 18%; 101¥¼±µ¨ü¹L¨ä¥LªvÀøªº¯f¤HORR 24.8%

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Á`¥­§¡¤ÏÀ³´Ámedian duration of response= 12.5¤ë (range, 1.0 to 23.3)

PD-L1 expression>=50%ªº¯f¤HÁ`¥­§¡¤ÏÀ³´Á= 12.5¤ë (range, 2.1 to 23.3)

PD-L1 expression 1%~49%ªº¯f¤HÁ`¥­§¡¤ÏÀ³´Á=7.2 months (range, 1.4 to 8.3)

PD-L1 expression <1%ªº¯f¤HÁ`¥­§¡¤ÏÀ³´Á=not reached(range, 1.0 to 10.8)

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PD-L1 expression¥Î50%¨Ó°µ¤ÁÂI

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Á`¦@73­Ó¯f¤HPD-L1 expression>=50%¡÷ ORR=45.2%;

PD-L1 expression>=50¤¤¡A¦³±µ¨ü¹L¨ä¥LªvÀøªº¯f¤H¡÷ ORR= 43.9%

PD-L1 expression>=50¤¤¡A¨S¦³±µ¨ü¹L¨ä¥LªvÀøªº¯f¤H¡÷ ORR=50.0%

©Ò¦³PD-L1 expression>=50%ªº¯f¤H¡÷mPFS=6.3¤ë

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PD-L1 expression>=50¤¤¡A¨S¦³±µ¨ü¹L¨ä¥LªvÀøªº¯f¤H¡÷mPFS= 12.5 months

©Ò¦³PD-L1 expression>=50%ªº¯f¤H¡÷mOS=13.7 months to notreached

PD-L1 expression>=50¤¤¡A¦³±µ¨ü¹L¨ä¥LªvÀøªº¯f¤H¡÷mOS= 9.3 months to not reached

PD-L1 expression>=50¤¤¡A¨S¦³±µ¨ü¹L¨ä¥LªvÀøªº¯f¤H¡÷mOS=not reached to not reached

PD-L1 expression>=50%ªºmPFS & mOS³£¤ñPD-L1 expression<1% & PD-L1 expression 1%~49%ªº¦n«Ü¦h¡I

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Go go Polaris!

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¦A¬Ý¬Ý¦Ñ´­´ÜÂIªº©ú¤é¥Í§ÞªÑ¤ý¡÷¥_·¥¬P¡I¤½§i¨p¶Ò9000±i¬O¤½§i¡A²{¦b¬O¦¬¨¬´Ú¶µ¡I¦¬¨¬´Ú¶µ¡I¦¬¨¬´Ú¶µ¡I

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§ó±N»´¨úX®®(¥ý¸ò¦Ñ¥v¤jsay sorry¡AÁn©ú¸òÃÄ©M¤½¥qµLÃö)¡B¦A¤U¤@«°¡I(¦Ñ´­µ£¤ß¤@°_¡A¤ñ»ù¯ÂÄݦnª±)

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·|­û¡G§ë¸êªÌ10141485  µoªí®É¶¡:2017/8/15 ¤U¤È 10:04:16²Ä 288 ½g¦^À³
1.¨Æ¹êµo¥Í¤é:106/08/15

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·|­û¡Gccc10136060  µoªí®É¶¡:2017/8/14 ¤U¤È 06:38:44²Ä 286 ½g¦^À³
The 18th World Conference on Lung Cancer of the International Association for the Study of Lung Cancer (IASLC) will take place from October 15 ¡V 18, 2017, in Yokohama, Japan

wclc2017.iaslc.org/conference-information/welcome-message/

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¸UºñÂO¤¤¤@ÂI¬õ¡A¤µ¤Ñ¤@¤ùºñªoªo¡A¤j³¡¤À¥Í§ÞªÑ¤]¶^ªº¬n¤C§á¤K¡A¦ý¥_·¥¬P¨ÌµM²H©w¨«¦Û¤vªº¸ô¡AÄ~Äò´ÂµÛ¥Ø¼Ð«e¶i!

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Go go Polaris!

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¤µ¤Ñ¦Ñ´­·Q±a¦U¦ì¬Ý¬Ý¬Q¤é©Ò¹w§iªº¡A

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2013¦~µoªíªºªÍÀù¼Ð¹v·sÃÄ¡G§´´_§J½¤¦ç¿õ(Afatinib)¡A¥D­n¾A¥Î©ó«D¤p²Ó­MªÍÀùªvÀø¡A³o¤]¬O¥xÆW

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Afatinib¥D­n¬OªvÀø¹ï²{¦³ªÍÀù¼Ð¹vªvÀøÃĪ«ªºIRESA(¦ã·ç²ï)¨ã¦³§ÜÃĩʪº±wªÌ¡AÄݤfªA¾¯«¬ªº¼Ð¹vÃĪ«

¼w°êÃļt¦ÊÆF¨Î(Boehringer-Ingelheim)ªºNintedanib+Cis+PemªºLUME-Meso study

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LUME-Meso: Design and Rationale of the Phase III Part of a Placebo-Controlled Study

of Nintedanib and Pemetrexed/Cisplatin Followed by Maintenance Nintedanib in Patients

With Unresectable Malignant Pleural Mesothelioma

Clin Lung Cancer 2017 Mar 22

Clinical trial identifier: NCT01907100

Nintedanib(¤fªA¨C¤Ñ¨â¦¸), ¾÷Âà©Mavastin¤@¼Ë¬OVEGFªº¼Ð¹vÃĪ«,

Nintedanib (Ofev) ³æ¤@¥ÎÃÄ´¿³QUSA and EU®Ö­ã¥Î©óidiopathic pulmonary fibrosis.

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locally advanced, metastatic or locally recurrent adenocarcinoma typeªºNSCLC«D¤p²Ó­MªÍÀù.

Chemo-naive patients(¥¼±µ¨ü¹L¤ÆÀø) from 27 countries

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randomized (1:1)

6 cycles of pemetrexed (500 mg/m2)/cisplatin (75 mg/m2) on Day 1 plus nintedanib

(200 mg bid) or placebo on Days 2-21.

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Primary endpoint= PFS

Secondary endpoint= OS, ORR, DCR

Phase 2¦b2016 WCLC(¥@¬ÉªÍÀù¤j·|)¤½¥¬ªº¼Æ¾Ú

87­Ó¯f¤H

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Estimated Study Completion Date: October 30, 2019

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ÄY­«°Æ§@¥Î= nintedanib+Cis+Pem²Õ36% vs Cis+Pem²Õ42%--¥[¤Fnintedanib¤Ï¦Ó°Æ§@¥ÎÅܤp¡H

>=grade 3 AEs= nintedanib+Cis+Pem34% vs Cis+Pem²Õ 10%--­ì¨ÓÁÙ¬OÅÜÄY­«¤F¡I

ALT increase= nintedanib+Cis+Pem14% vs Cis+Pem²Õ2%

gamma glutamyltransferase increase nintedanib+Cis+Pem14% vs Cis+Pem²Õ0%

¡´³Ì³Ì­«­nªº¬O¡÷nintedanib+Cis+Pem²Õphase 3¥u¦¬epitheloid type¡I¥u¦¬epitheloid type¡I¥u¦¬epitheloid type¡I

¬U¤l¬D³nªº¦Y¡I¦]¬°phase 2ªº¼Æ¾Ú§i¶DBoehringer-Ingelheim¡A¬D¾Ônon-epitheloid¬Onintedanib°µ¤£¨ìªº¡I

¦A·Å²ß¤@¤U¥_·¥¬P

²Ä¤K½b¡÷ªÍ¶¡¥ÖÀùnon-epithelioid MPM phaseII/IIIÁp¦X¥ÎÃÄADI+Cis+Pemªº¦¬®×¶i«×(Phase II±N¦¬®×176¤H¡A88:88¡A¹ï·Ó²Õ¬°Placebo+Cis+Pem)

¤]´N¬O©Ò¿×ªºATomic-meso study (ClinicalTrials.gov Identifier:NCT02709512)

FDA¤w¦P·N¥u­nPhase IIªºORR>=1­¿¥H¤W(¹w¦ô¹ï·Ó²Õ:¹êÅç²ÕORR=15%:35%)¡A´N·|ª½±µµ¹ÃÄÃÒ¡I

±q2017 ASCOªºTRAP expansion study(31­Ó¯f¤H)§i¶D§Ú­ÌADI+Cis+Pemªº

PR= 35.5% (95% CI 19.2%-54.6%)

DCR= 93.5% (95% CI 78.6%-99.2%)

ºâºâ­n²Å¦XFDAªº±ø¥ó¡AADI+Cis+PemªºORR­n¤ñCis+PemªºORR>=1­¿ªº³Óºâ¦³¦h¤Ö¡H

¨Ï¥Îz proportional test, two tail

Cis+Pem (88¤H) vs. ADI+Cis+Pem(88¤H)

p=0.05, power=90%ªº±¡ªp¤U¡÷Cis+PemªºORR­Y=15%«hADI+Cis+PemªºORR¥²¶·=36%

p=0.05, power=80%ªº±¡ªp¤U¡÷Cis+PemªºORR­Y=15%«hADI+Cis+PemªºORR¥²¶·=32.9%

p=0.05, power=90%ªº±¡ªp¤U¡÷Cis+PemªºORR­Y=13.9%«hADI+Cis+PemªºORR¥²¶·=34.6%

p=0.05, power=80%ªº±¡ªp¤U¡÷Cis+PemªºORR­Y=13.9%«hADI+Cis+PemªºORR¥²¶·=31.5%

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