The prognostic impact of KRAS, TP53, STK11 and KEAP1 mutations and their influence on the NLR in NSCLC patients treated with immunotherapy

被引：10

作者：

Proulx-Rocray, Francis ^{[1
]}

Routy, Bertrand ^{[1
,2
]}

Nassabein, Rami ^{[1
]}

Belkaid, Wiam ^{[2
]}

Tran-Thanh, Danh ^{[2
]}

Malo, Julie ^{[2
]}

Tonneau, Marion ^{[2
]}

El Ouarzadi, Omar ^{[2
]}

Florescu, Marie ^{[1
,2
]}

Tehfe, Mustapha ^{[1
,2
]}

Blais, Normand ^{[1
,2
]}

机构：

[1] Ctr Hosp Univ Montreal CHUM, Med Oncol Dept, 1051 Sanguinet St, Montreal, PQ, Canada

[2] Ctr Hosp Univ Montreal, Pathol Dept, 1051 Sanguinet St, Montreal, PQ, Canada

来源：

CANCER TREATMENT AND RESEARCH COMMUNICATIONS | 2023年 / 37卷

关键词：

NSCLC; Immunotherapy; KRAS; STK11; KEAP1; CELL LUNG-CANCER; IMMUNE CHECKPOINT INHIBITORS; PD-1; BLOCKADE; OPEN-LABEL; PEMBROLIZUMAB; DOCETAXEL; SUSCEPTIBILITY; ATEZOLIZUMAB; CHEMOTHERAPY; INFLAMMATION;

D O I：

10.1016/j.ctarc.2023.100767

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Background: PD-L1 expression is used to predict NSCLC response to ICIs, but its performance is suboptimal. The impact of KRAS mutations in these patients is unclear. Studies evaluating co-mutations in TP53, STK11 and KEAP1 as well as the NLR showed that they may predict the benefit of ICIs. Patients & methods: This is a retrospective study of patients with NSCLC treated with ICIs at the CHUM between July 2015 and June 2020. OS and PFS were compared using Kaplan-Meier and logrank methods. Co-mutations in TP53, STK11 and KEAP1 as well as the NLR were accounted for. ORR and safety were compared using Wald method. Results: From 100 patients with known KRAS status, 50 were mutated (KRASMut). Mutation in TP53, STK11 and KEAP1 were present, and their status known in, respectively, 19/40 (47.5 %), 8/39 (20.5 %) and 4/38 (10.5 %) patients. STK11Mut and KEAP1Mut were associated with shorter overall survival when compared with wild type tumors (respectively median OS of 3.3 vs 20.4, p = 0.0001 and 10.1 vs 17.7, p = 0.24). When KRAS status was compounded with STK11/KEAP1, KRASMut trended to a better prognosis in STK11+KEAP1WT tumors (median OS 21.1 vs 15.8 for KRASWT, p = 0.15), but not for STK11+/-KEAP1Mut tumors. The NLR was strongly impacted by STK11 (6.0Mut vs 3.6WT, p = 0.014) and TP53 (3.2Mut vs 4.8WT, p = 0.048), but not by KEAP1 or KRAS mutations. Conclusion: STK11Mut and KEAP1Mut are adverse predictors of ICI therapy benefit. The NLR is strongly impacted by STK11Mut but not by KEAP1Mut, suggesting differences in their resistance mechanism. In STK11-KEAP1WT tumors, KRASMut seem associated with improved survival in NSCLC patients treated with ICIs. MicroAbstract: Response of NSCLC to immunotherapy is not easily predictable. We conducted a retrospective study in 100 patients with NSCLC and a known KRAS status. By accounting for different co-mutations, KRAS mutation was found to be associated with a better median overall survival in STK11 and KEAP1 wild-type tumors (21.1 vs 15.8, p = 0.15). NLR was impacted by STK11, but not KEAP1 mutation, suggesting a difference in their resistance mechanism.

引用

页数：8

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