KRASG12C/TP53 co-mutations identify long-term responders to first line palliative treatment with pembrolizumab monotherapy in PD-L1 high (≥50%) lung adenocarcinoma

被引:41
作者
Frost, Nikolaj [1 ,2 ,3 ]
Kollmeier, Jens [4 ]
Vollbrecht, Claudia [1 ,2 ,5 ]
Grah, Christian [6 ]
Matthes, Burkhard [6 ]
Pultermann, Dennis [1 ,2 ,3 ]
von Laffert, Maximilian [1 ,2 ,5 ]
Lueders, Heike [7 ]
Olive, Elisabeth [7 ]
Raspe, Matthias [1 ,2 ,3 ]
Mairinger, Thomas [8 ]
Ochsenreither, Sebastian [1 ,2 ,9 ]
Blum, Torsten [4 ]
Hummel, Michael [1 ,2 ,5 ]
Suttorp, Norbert [1 ,2 ,3 ]
Witzenrath, Martin [1 ,2 ,3 ]
Grohe, Christian [7 ]
机构
[1] Charite Univ Med Berlin, Berlin, Germany
[2] Humboldt Univ, Freie Univ Berlin, Berlin, Germany
[3] Berlin Inst Hlth, Dept Infect Dis & Pulm Med, Berlin, Germany
[4] Lungenklin Heckeshorn, Helios Klinikum Emil von Behring, Berlin, Germany
[5] Berlin Inst Hlth, Dept Pathol, Berlin, Germany
[6] Gemeinschaftskrankenhaus Havelhohe, Dept Pneumonol, Berlin, Germany
[7] Klin Pneumol Evangel Lungenklin Berlin Buch, Berlin, Germany
[8] Helios Klinikum Emil von Behring, Dept Pathol, Berlin, Germany
[9] Berlin Inst Hlth, Dept Hematol Oncol & Tumorimmunol, Berlin, Germany
关键词
Non-small cell lung cancer (NSCLC); checkpoint inhibitors; KRAS mutations; TP53; mutations; IMMUNE CHECKPOINT INHIBITORS; PREDICTIVE-VALUE; KRAS MUTATIONS; CANCER; ASSOCIATION; EXPRESSION; BLOCKADE; OUTCOMES; TP53;
D O I
10.21037/tlcr-20-958
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Background: Pembrolizumab is a standard of care as first line palliative therapy in PD-L1 overexpressing (>= 50%) non-small cell lung cancer (NSCLC). This study aimed at the identification of KRAS and TP53-defined mutational subgroups in the PD-L1 high population to distinguish long-term responders from those with limited benefit. Methods: In this retrospective, observational study, patients from 4 certified lung cancer centers in Berlin, Germany, having received pembrolizumab monotherapy as first line palliative treatment for lung adenocarcinoma (LuAD) from 2017 to 2018, with PD-L1 expression status and targeted NGS data available, were evaluated. Results: A total of 119 patients were included. Rates for KRAS, TP53 and combined mutations were 52.1%, 47.1% and 21.9%, respectively, with no association given between KRAS and TP53 mutations (P=0.24). By trend, PD-L1 expression was higher in KRAS-positive patients (75% vs. 65%, P=0.13). Objective response rate (ORR), median progression-free survival (PFS) and overall survival (OS) in the KRAS(G12C) group (n=32, 51.6%) were 63.3%, 19.8 months (mo.) and not estimable (NE), respectively. Results in KRAS(other) and wild type patients were similar and by far lower (42.7%, P=0.06; 6.2 mo., P<0.001; 23.4 mo., P=0.08). TP53 mutations alone had no impact on response and survival. However, KRAS(G12C)/TP53 co-mutations (n=12) defined a subset of long-term responders (ORR 100.0%, PFS 33.3 mo., OS NE). In contrast, patients with KRAS(other)/TP53 mutations showed a dismal prognosis (ORR 27.3%, P=0.002; PFS 3.9 mo., P=0.001, OS 9.7 mo., P=0.02). Conclusions: A comprehensive assessment of KRAS subtypes and TP53 mutations allows a highly relevant prognostic differentiation of patients with metastatic, PD-L1 high LuAD treated upfront with pembrolizumab.
引用
收藏
页码:737 / 752
页数:16
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