Izazi zika-Dong-Wan Kim zaseSeoul National University Hospital eSouth Korea zizonikeza umbiko ngomlomo mayelana nomhlangano okhethekile womdlavuza wamaphaphu ongewona omncane we-metastatic eMhlanganweni Wonyaka wama-52 we-American Society of Oncology (ASCO) eChicago ngoJuni 6. , Isikhathi sendawo sango-2016: umbiko wokuqala Ukuhlolwa komtholampilo okubalulekile kwesigaba II esibalulekile sokusebenza nokuphepha kokusebenzisa i-Brigatinib (BRG) ezigulini ezinomdlavuza we-ALK + crizotinib-resistant non-small cell lung cancer (NSCLC).
I-BRG iyi-oral tyrosine kinase inhibitor (TKI) ngesikhathi sokubuka. Inomsebenzi we-preclinical ngokumelene nokuhlelwa kabusha kwe-ALK kanye nezinguquko ezimelana ne-CRZ. Lesi sivivinyo sesigaba 1/2 somtholampilo sibonisa amathuba amahle e-BRG. Kokubili izinga lokuphendula le-BRG kanye nama-AE angahluka ngethamo lokuqala, ngakho-ke, kulolu cwaningo oluqhubekayo olungahleliwe, izinketho ezimbili zokusebenzisa i-BRG zihloliwe.
Imiphumela yalolu cwaningo ibonisa ukuthi i-BRG inempendulo ecacile yokwelashwa, i-PFS ezinzile, nezici zokuphepha ezamukelekayo. Ngakho-ke, bahlela ukwenza uhlolo lomtholampilo lwesigaba III oluqhathanisa ne-CRZ BRG 90 mg qd * izinsuku ezingu-7 kanye no-180 mg qd ezigulini ezine-ALK + i-NSCLC ethuthukisiwe ne-CRZ ezigulini ezingazange zisebenzise i-TKI.
Kulolu cwaningo, iziguli ≥ ezineminyaka engu-18 ubudala, i-ALK + NSCLC yathuthuka ngemva kokusebenzisa i-CRZ futhi azikho ezinye iziguli ze-ALK TKI ezazitholakala. Ngokusho kokuthi isiguli sinesimo sokuqala se-metastasis ye-intracranial kanye nempendulo engcono kakhulu ekusetshenzisweni kwangaphambili kwe-CRZ, iziguli zahlukaniswa ngokungahleliwe zibe yi-1: 1 yomlomo BRG 90 mg qd (iqembu A) noma 90 mg qd x 7d kanye ne-180 mg. qd (iqembu B).
The primary endpoint is observation-assessment-confirmation of ORR per RECIST v1.1. Key secondary endpoints include PFS and IRC to assess formal ORR and CNS responses. 222 patients were randomly divided into A / B group, n = 112 / n = 110. As of September 21, 2015, the last patient was included. The average age was 51/57 years old, and 71% / 67% had brain metastases.
The proportion of patients in groups A and B was 63% / 74% while the experiment was still in progress on December 7, 2015, and the average duration of treatment was 25 weeks / 23 weeks. Observation-assessment of group A: 46% of confirmed ORR (39 confirmed reactions + 12 single responses waiting to be confirmed), including 1 confirmed complete response (CRs); ORR of group B: 54% (49 confirmed reactions) + 10 responses awaiting confirmation), including 5 confirmed CRs. The median PFS for A / B is 8.8 months / 11.1 months.
Izehlakalo ezinobuthi eqenjini A / B zazingama-44/25, ukwelashwa okuphuthumayo okuvame kakhulu ama-AEs ebangeni ≥ 3, iqembu A / B lifakiwe: ukwanda kwe-CPK (3% / 8%), umfutho wegazi ophakeme (4% / 5%), ukutheleleka kwamaphaphu (3% / 5%), ukuqubuka (1% / 4%), ukukhuphuka kwe-lipids yegazi (3% / 2%) kanye nenyumoniya (2% / 3%). Ku-6% yeziguli, izenzakalo ze-pulmonary zenzeka ngesikhathi sokuqala (3% ≥ ibanga lesi-3 phakathi nezinsuku ze-7 zokuqaliswa kokwelashwa); lesi sigameko asizange sibonwe eqenjini B futhi senyukele ku-180 mg phakathi nezinsuku ze-7 zokuqaliswa kokwelashwa nangemva kwalokho. Ukuphazamiseka kanye nokwehliswa kweqembu le-A/B ngenxa yama-AE bekungu-3% / 6% no-7% / 18%, ngokulandelana.
