|Table of Contents|

Analysis of molecular subtypes，treatment and outcomes in advanced non-small cell lung cancer patients with KRAS mutation

Journal Of Modern Oncology[ISSN:1672-4992/CN:61-1415/R]

Issue:
2023 04
Page:
669-674
Research Field:
Publishing date:

Info

Title:
Analysis of molecular subtypes，treatment and outcomes in advanced non-small cell lung cancer patients with KRAS mutation
Author(s):
WANG Diming1; YE Wei2; SHI Qingming1
1.Department of Oncology;2.Department of Pathology,Anhui Chest Hospital,Anhui Hefei 230022,China.
Keywords:
non-small cell lung cancer; KRAS mutation; TP53 co-mutation; treatment; outcome
PACS:
R734.2
DOI:
10.3969/j.issn.1672-4992.2023.04.014
Abstract:
Objective:To analyze the clinicopathological features,molecular variants,treatment options,and outcomes in patients with Kirsten rat sarcoma (KRAS) mutated advanced non-small cell lung cancer (NSCLC).Methods:We retrospectively analyzed the clinicopathological data of 33 patients with advanced KRAS-mutated NSCLC in our hospital between January 2019 and January 2022.The association between KRAS subtypes,TP53 co-mutations,and different treatment regimens and survival prognosis was analyzed.Results:A total of 33 patients with advanced KRAS-mutated NSCLC were included,with males accounting for approximately 90.9%(30/33).The most common KRAS subtype was p.G12C(14/33,42.4%).In addition,there were no significant differences in progression-free survival (PFS)(6.5 months vs 7.0 months,P=0.799) and overall survival (OS)(18.0 months vs 24.0 months,P=0.266) between the KRAS p.G12C and other KRAS mutations.In subgroup analysis,immunotherapy combined with chemotherapy prolonged PFS(13.5 months vs 7.5 months vs 5.5 months,P=0.033) compared with chemotherapy+anti-angiogenic and chemotherapy,but no significant difference was observed in OS(25.0 months vs 18.0 months vs 25.0 months,P=0.854).The PFS(5.5 months vs 7.5 months,P=0.019) and OS(18.0 months vs 28.0 months,P=0.004) were significantly shorter in KRAS+/TP53+ NSCLC compared with KRAS+/TP53-NSCLC.According to the multivariate Cox analysis,TP53 co-mutations(HR=3.394,P=0.005) and treatment regimens(HR=0.473,P=0.003) were the prognostic factors for PFS,and TP53 co-mutations(HR=8.235,P=0.004) was an independent prognostic factor for OS.Conclusion:This study revealed that the males in Chinese advanced KRAS mutated NSCLC patients were relatively common and p.G12C was the most common molecular subtype.Immunotherapy combined with chemotherapy might prolong PFS in advanced KRAS+NSCLC,but the further investigation should be needed.TP53 co-mutations may be a poor prognostic factor for advanced KRAS+NSCLC.The treatment and prognosis of patients with KRAS and TP53 co-mutations in advanced NSCLC need to be further explored.

References:

［1］SIEGEL RL,MILLER KD,FUCHS HE,et al.Cancer statistics,2022［J］.CA Cancer J Clin,2022,72(1):7-33.
［2］ROY-CHOWDHURI S.Molecular pathology of lung cancer ［J］.Surgical Pathology Clinics,2021,14(3):369-377.
［3］TAN AC,TAN DSW.Targeted therapies for lung cancer patients with oncogenic driver molecular alterations ［J］.J Clin Oncol,2022,40(6):611-625.
［4］LEE HJ,JEONG GH,LI H,et al.Efficacy and safety of epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) monotherapy for advanced EGFR-mutated non-small cell lung cancer:systematic review and meta-analysis ［J］.Eur Rev Med Pharmacol Sci,2021,25(20):6232-6244.
［5］KHAN M,LIN J,LIAO G,et al.ALK inhibitors in the treatment of ALK positive NSCLC ［J］.Frontiers in Oncology,2018,8:557.
［6］SUNAGA N,MIURA Y,KASAHARA N,et al.Targeting oncogenic KRAS in non-small-cell lung cancer ［J］.Cancers,2021,13(23):5956.
［7］CAI D,HU C,LI L,et al.The prevalence and prognostic value of KRAS co-mutation subtypes in Chinese advanced non-small cell lung cancer patients ［J］.Cancer Medicine,2020,9(1):84-93.
［8］GOULDING RE,CHENOWETH M,CARTER GC,et al.KRAS mutation as a prognostic factor and predictive factor in advanced/metastatic non-small cell lung cancer:A systematic literature review and meta-analysis ［J］.Cancer Treatment and Research Communications,2020,24:100200.
［9］SHEN M,QI R,REN J,et al.Characterization with KRAS mutant is a critical determinant in immunotherapy and other multiple therapies for non-small cell lung cancer ［J］.Frontiers in Oncology,2021,11:780655.
［10］WEST HJ,MCCLELAND M,CAPPUZZO F,et al.Clinical efficacy of atezolizumab plus bevacizumab and chemotherapy in KRAS-mutated non-small cell lung cancer with STK11,KEAP1,or TP53 comutations:subgroup results from the phase III IMpower150 trial ［J］.Journal for Immunotherapy of Cancer,2022,10(2):e003027.
［11］JEANSON A,TOMASINI P,SOUQUET-BRESSAND M,et al.Efficacy of immune checkpoint inhibitors in KRAS-mutant non-small cell lung cancer (NSCLC) ［J］.J Thorac Oncol,2019,14(6):1095-1101.
［12］SKOULIDIS F,LI BT,DY GK,et al.Sotorasib for lung cancers with KRAS p.G12C mutation ［J］.The New England Journal of Medicine,2021,384(25):2371-2381.
［13］JANNE PA,RIELY GJ,GADGEEL SM,et al.Adagrasib in non-small-cell lung cancer harboring a KRAS(G12C) mutation ［J］.The New England Journal of Medicine,2022,387(2):120-131.
［14］PIRLOG R,PITON N,LAMY A,et al.Morphological and molecular characterization of KRAS G12C-mutated lung adenocarcinomas ［J］.Cancers,2022,14(4):1030.
［15］JUDD J,ABDEL KARIM N,KHAN H,et al.Characterization of KRAS mutation subtypes in non-small cell lung cancer ［J］.Molecular Cancer Therapeutics,2021,20(12):2577-2584.
［16］BURNS EA,ENSOR JE,HSU J,et al.Outcomes and prognostic contributors in patients with KRAS mutated non-small cell pulmonary adenocarcinomas:a single institution experience ［J］.J Thorac Dis,2021,13(8):4785-4796.
［17］SPIRA AI,TU H,AGGARWAL S,et al.A retrospective observational study of the natural history of advanced non-small-cell lung cancer in patients with KRAS p.G12C mutated or wild-type disease ［J］.Lung Cancer,2021,159:1-9.
［18］LIU Y,LI H,ZHU J,et al.The prevalence and concurrent pathogenic mutations of KRAS (G12C) in Northeast Chinese non-small-cell lung cancer patients ［J］.Cancer Management and Research,2021,13:2447-2454.
［19］GADGEEL S,RODRIGUEZ-ABREU D,FELIP E,et al.KRAS mutational status and efficacy in KEYNOTE-189:Pembrolizumab (pembro) plus chemotherapy (chemo) vs placebo plus chemo as first-line therapy for metastatic non-squamous NSCLC ［J］.Annals of Oncology,2019,30:xi64-xi65.
［20］LEE J,TAN AC,ZHOU S,et al.Clinical characteristics and outcomes in advanced KRAS-mutated NSCLC:A multicenter collaboration in Asia (ATORG-005) ［J］.JTO Clinical and Research Reports,2022,3(1):100261.
［21］FAN Z,ZHANG Q,FENG L,et al.Genomic landscape and prognosis of patients with TP53-mutated non-small cell lung cancer ［J］.Annals of Translational Medicine,2022,10(4):188.
［22］QIN K,HOU H,LIANG Y,et al.Prognostic value of TP53 concurrent mutations for EGFR-TKIs and ALK-TKIs based targeted therapy in advanced non-small cell lung cancer:a meta-analysis ［J］.BMC Cancer,2020,20(1):328.
［23］LA FLEUR L,FALK-SORQVIST E,SMEDS P,et al.Mutation patterns in a population-based non-small cell lung cancer cohort and prognostic impact of concomitant mutations in KRAS and TP53 or STK11 ［J］.Lung Cancer,2019,130:50-58.
［24］TOMASINI P,MASCAUX C,JAO K,et al.Effect of coexisting KRAS and TP53 mutations in patients treated with chemotherapy for non-small-cell lung cancer ［J］.Clin Lung Cancer,2019,20(3):e338-e345.
［25］DONG ZY,ZHONG WZ,ZHANG XC,et al.Potential predictive value of TP53 and KRAS mutation status for response to PD-1 blockade immunotherapy in lung adenocarcinoma ［J］.Clin Cancer Res,2017,23(12):3012-3024.
［26］ARBOUR KC,JORDAN E,KIM HR,et al.Effects of co-occurring genomic alterations on outcomes in patients with KRAS-mutant non-small cell lung cancer ［J］.Clin Cancer Res,2018,24(2):334-340.
［27］FROST N,KOLLMEIER J,VOLLBRECHT C,et al.KRAS(G12C)/TP53 co-mutations identify long-term responders to first line palliative treatment with pembrolizumab monotherapy in PD-L1 high (≥50%) lung adenocarcinoma［J］.Translational Lung Cancer Research,2021,10(2):737-752.

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Last Update: 1900-01-01