Dong-Wan Kim nyanzvi kubva kuSeoul National University Hospital muSouth Korea ichapa chirevo chemuromo pamusangano unokosha wekenza yemapapu isiri-diki yekenza yemapapu pa52nd Annual Meeting yeAmerican Society of Oncology (ASCO) muChicago musi waChikumi 6. , 2016 nguva yemunharaunda: mushumo wekutanga An important randomized phase II kliniki yekuedza kwehutano uye kuchengeteka kwekushandisa Brigatinib (BRG) kune varwere vane ALK + crizotinib-resistant isiri-small cell lung cancer (NSCLC).
BRG inonzi oral tyrosine kinase inhibitor (TKI) munguva yekucherechedza. Iyo ine preclinical chiitiko ichipokana neAlK rearrangements uye CRZ-inodzivirira shanduko. Ichi chekiriniki chikamu 1/2 chiyedzo chinoratidza tarisiro yakanaka yeBRG. Ose ari maviri chiyero chemhinduro yeBRG uye maAE anogona kusiyana nedosi yekutanga, saka, muchidzidzo ichi chirikuenderera mberi, sarudzo mbiri dzekushandisa dzeBRG dzakaongororwa.
Mhedzisiro yechidzidzo ichi inoratidza kuti BRG ine mhinduro yakajeka pakurapa, yakagadzikana PFS, uye inogamuchirwa chengetedzo maitiro. Nokudaro, vanoronga kuita chikamu chechitatu chekliniki yekuedza kuenzanisa CRZ BRG 90 mg qd * 7 mazuva uye 180 mg qd kune varwere vane ALK + advanced NSCLC uye CRZ kune varwere vasina kushandisa TKI.
Muchiyedzo ichi, varwere ≥ makore gumi nemasere, ALK + NSCLC yakafambira mberi mushure mekushandisa CRZ uye hapana vamwe varwere veALK TKI vaivepo. Zvinoenderana nekuti murwere ane mamiriro ekutanga e intracranial metastasis uye mhinduro yakanakisa kukushandiswa kwekare kweCRZ, varwere vakakamurwa zvisina tsarukano mu18: 1 oral BRG 1 mg qd (boka A) kana 90 mg qd x 90d uye 7 mg. qd (B boka).
Mhedziso yekutanga ndeyekutarisa-kuongorora-kusimbisa kweORR pane RECIST v1.1. Makiyi echipiri ekupedzisira anosanganisira PFS uye IRC kuongorora zviri pamutemo ORR uye CNS mhinduro. Varwere ve222 vakaparadzaniswa zvisina kumira muboka reA / B, n = 112 / n = 110. Kubva munaSeptember 21, 2015, murwere wekupedzisira akabatanidzwa. Avhareji yezera yaive 51/57 yemakore, uye 71% / 67% yaive nehuropi metastases.
Chiyero chevarwere mumapoka A uye B chaiva 63% / 74% apo kuedza kwakanga kuchiri kuitika musi waDecember 7, 2015, uye nguva yenguva yekurapa yaiva mavhiki e25 / 23 mavhiki. Kucherechedza-kuongororwa kweboka A: 46% yeORR yakasimbiswa (39 yakasimbiswa maitiro + 12 mhinduro imwe chete yakamirira kusimbiswa), kusanganisira 1 yakasimbisa mhinduro yakakwana (CRs); ORR yeboka B: 54% (49 yakasimbiswa maitiro) + 10 mhinduro dzakamirira kusimbiswa), kusanganisira 5 yakasimbiswa CRs. Iyo yepakati PFS yeA / B ndeye 8.8 mwedzi / 11.1 mwedzi.
Zviitiko zvine chepfu muboka A / B zvaive 44/25, iyo yakajairika kurapwa kwekukurumidzira AEs yegiredhi ≥ 3, boka A / B raisanganisira: yakawedzera CPK (3% / 8%), hypertension (4% / 5%), Utachiona hwemapapu. (3% / 5%), mapundu (1% / 4%), yakakwira lipids yeropa (3% / 2%) uye mabayo (2% / 3%). Mu6% yevarwere, zviitiko zvemapapu zvakaitika panguva yekutanga (3% ≥ giredhi 3 mukati me7 mazuva ekutanga kurapwa); chiitiko ichi hachina kuonekwa muboka B uye chakawedzera kusvika 180 mg mukati memazuva 7 ekutanga kurapwa uye pashure. Kuvhiringidzwa uye kudzikiswa kweboka reA / B nekuda kweAEs kwaive 3% / 6% uye 7% / 18%, zvichiteerana.
