作者
Ferdinandos Skoulidis, Michael E Goldberg, Danielle M Greenawalt, Matthew D Hellmann, Mark M Awad, Justin F Gainor, Alexa B Schrock, Ryan J Hartmaier, Sally E Trabucco, Laurie Gay, Siraj M Ali, Julia A Elvin, Gaurav Singal, Jeffrey S Ross, David Fabrizio, Peter M Szabo, Han Chang, Ariella Sasson, Sujaya Srinivasan, Stefan Kirov, Joseph Szustakowski, Patrik Vitazka, Robin Edwards, Jose A Bufill, Neelesh Sharma, Sai-Hong I Ou, Nir Peled, David R Spigel, Hira Rizvi, Elizabeth Jimenez Aguilar, Brett W Carter, Jeremy Erasmus, Darragh F Halpenny, Andrew J Plodkowski, Niamh M Long, Mizuki Nishino, Warren L Denning, Ana Galan-Cobo, Haifa Hamdi, Taghreed Hirz, Pan Tong, Jing Wang, Jaime Rodriguez-Canales, Pamela A Villalobos, Edwin R Parra, Neda Kalhor, Lynette M Sholl, Jennifer L Sauter, Achim A Jungbluth, Mari Mino-Kenudson, Roxana Azimi, Yasir Y Elamin, Jianjun Zhang, Giulia C Leonardi, Fei Jiang, Kwok-Kin Wong, J Jack Lee, Vassiliki A Papadimitrakopoulou, Ignacio I Wistuba, Vincent A Miller, Garrett M Frampton, Jedd D Wolchok, Alice T Shaw, Pasi A Jänne, Philip J Stephens, Charles M Rudin, William J Geese, Lee A Albacker, John V Heymach
发表日期
2018/7/1
期刊
Cancer discovery
卷号
8
期号
7
页码范围
822-835
出版商
American Association for Cancer Research
简介
KRAS is the most common oncogenic driver in lung adenocarcinoma (LUAC). We previously reported that STK11/LKB1 (KL) or TP53 (KP) comutations define distinct subgroups of KRAS-mutant LUAC. Here, we examine the efficacy of PD-1 inhibitors in these subgroups. Objective response rates to PD-1 blockade differed significantly among KL (7.4%), KP (35.7%), and K-only (28.6%) subgroups (P < 0.001) in the Stand Up To Cancer (SU2C) cohort (174 patients) with KRAS-mutant LUAC and in patients treated with nivolumab in the CheckMate-057 phase III trial (0% vs. 57.1% vs. 18.2%; P = 0.047). In the SU2C cohort, KL LUAC exhibited shorter progression-free (P < 0.001) and overall (P = 0.0015) survival compared with KRASMUT;STK11/LKB1WT LUAC. Among 924 LUACs, STK11/LKB1 alterations were the only marker significantly associated with PD-L1 negativity in TMBIntermediate/High LUAC …
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F Skoulidis, ME Goldberg, DM Greenawalt… - Cancer discovery, 2018