Survival Outcome According to KRAS Mutation Status in Newly Diagnosed Patients with Stage IV Non-small Cell Lung Cancer Treated with Platinum Doublet Chemotherapy

Overview

Journal Oncotarget

Specialty Oncology

Date 2015 Oct 17

PMID 26471290

Citations 15

Authors

Anna K Brady

Jonathan D McNeill

Brendan Judy

Joshua Bauml

Tracey L Evans

Roger B Cohen

Corey Langer

Anil Vachani

Charu Aggarwal

Affiliations

Soon will be listed here.

Abstract

Introduction: Mutations (MT) of the KRAS gene are the most common mutation in non-small cell lung cancer (NSCLC), seen in about 20-25% of all adenocarcinomas. Effect of KRAS MT on response to cytotoxic chemotherapy is unclear.

Methods: We undertook a single-institution retrospective analysis of 93 consecutive patients with stage IV NSCLC adenocarcinoma with known KRAS and EGFR MT status to determine the association of KRAS MT with survival. All patients were treated between January 1, 2008 and December 31, 2011 with standard platinum based chemotherapy at the University of Pennsylvania. Overall and progression free survival were analyzed using Kaplan-Meier and Cox proportional hazard methods.

Results: All patients in this series received platinum doublet chemotherapy, and 42 (45%) received bevacizumab. Overall survival and progression free survival for patients with KRAS MT was no worse than for patients with wild type KRAS. Median overall survival for patients with KRAS MT was 19 months (mo) vs. 15.6 mo for KRAS WT, p = 0.34, and progression-free survival was 6.2 mo in patients with KRAS MT vs. 7 mo in patients with KRAS WT, p = 0.51. In multivariable analysis including age, race, gender, and ECOG PS, KRAS MT was not associated with overall survival (HR 1.12, 95% CI 0.58-2.16, p = 0.74) or progression free survival (HR 0.80, 95% CI 0.48-1.34, p = 41). Of note, receipt of bevacizumab was associated with improved overall survival only in KRAS WT patients (HR 0.34, p = 0.01).

Conclusions: KRAS MT are not associated with inferior progression-free and overall survival in advanced NSCLC patients treated with standard first-line platinum-based chemotherapy.

Citing Articles

MYC and KRAS cooperation: from historical challenges to therapeutic opportunities in cancer.

Casacuberta-Serra S, Gonzalez-Larreategui I, Capitan-Leo D, Soucek L Signal Transduct Target Ther. 2024; 9(1):205.

PMID: 39164274 PMC: 11336233. DOI: 10.1038/s41392-024-01907-z.

Additional impact of genetic ancestry over race/ethnicity to prevalence of KRAS mutations and allele-specific subtypes in non-small cell lung cancer.

Wang X, Hou K, Ricciuti B, Alessi J, Li X, Pecci F HGG Adv. 2024; 5(3):100320.

PMID: 38902927 PMC: 11452329. DOI: 10.1016/j.xhgg.2024.100320.

Assessing the prognostic value of mutation combined with tumor size in stage I-II non-small cell lung cancer: a retrospective analysis.

Eklund E, Mourad A, Wiel C, Sayin S, Fagman H, Hallqvist A Front Oncol. 2024; 14:1396285.

PMID: 38884086 PMC: 11176435. DOI: 10.3389/fonc.2024.1396285.

KRAS as a Prognostic and Predictive Marker in Metastatic Non-Small Cell Lung Carcinoma: A Systematic Review.

Fatima S, Pansuriya N, Lakhani A, Madhuri S, Ajmal R, Clementina R Cureus. 2024; 16(5):e60061.

PMID: 38860089 PMC: 11162968. DOI: 10.7759/cureus.60061.

A single center analysis of first-line treatment in advanced KRAS mutant non-small cell lung cancer: real-world practice.

Liu Y, Gao Y, Wang Y, Zhao C, Zhang Z, Li B BMC Cancer. 2022; 22(1):1175.

PMID: 36376839 PMC: 9664628. DOI: 10.1186/s12885-022-10236-9.

References

Slebos R, Kibbelaar R, Dalesio O, Kooistra A, Stam J, Meijer C . K-ras oncogene activation as a prognostic marker in adenocarcinoma of the lung. N Engl J Med. 1990; 323(9):561-5. DOI: 10.1056/NEJM199008303230902. View

Mascaux C, Iannino N, Martin B, Paesmans M, Berghmans T, Dusart M . The role of RAS oncogene in survival of patients with lung cancer: a systematic review of the literature with meta-analysis. Br J Cancer. 2004; 92(1):131-9. PMC: 2361730. DOI: 10.1038/sj.bjc.6602258. View

Eberhard D, Johnson B, Amler L, Goddard A, Heldens S, Herbst R . Mutations in the epidermal growth factor receptor and in KRAS are predictive and prognostic indicators in patients with non-small-cell lung cancer treated with chemotherapy alone and in combination with erlotinib. J Clin Oncol. 2005; 23(25):5900-9. DOI: 10.1200/JCO.2005.02.857. View

Tsao M, Aviel-Ronen S, Ding K, Lau D, Liu N, Sakurada A . Prognostic and predictive importance of p53 and RAS for adjuvant chemotherapy in non small-cell lung cancer. J Clin Oncol. 2007; 25(33):5240-7. DOI: 10.1200/JCO.2007.12.6953. View

Zhu C, da Cunha Santos G, Ding K, Sakurada A, Cutz J, Liu N . Role of KRAS and EGFR as biomarkers of response to erlotinib in National Cancer Institute of Canada Clinical Trials Group Study BR.21. J Clin Oncol. 2008; 26(26):4268-75. DOI: 10.1200/JCO.2007.14.8924. View

Karapetis C, Khambata-Ford S, Jonker D, OCallaghan C, Tu D, Tebbutt N . K-ras mutations and benefit from cetuximab in advanced colorectal cancer. N Engl J Med. 2008; 359(17):1757-65. DOI: 10.1056/NEJMoa0804385. View

Mok T, Wu Y, Thongprasert S, Yang C, Chu D, Saijo N . Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma. N Engl J Med. 2009; 361(10):947-57. DOI: 10.1056/NEJMoa0810699. View

Ferte C, Besse B, Dansin E, Parent F, Buisine M, Copin M . Durable responses to Erlotinib despite KRAS mutations in two patients with metastatic lung adenocarcinoma. Ann Oncol. 2010; 21(6):1385-1387. DOI: 10.1093/annonc/mdq153. View

Kalikaki A, Koutsopoulos A, Hatzidaki D, Trypaki M, Kontopodis E, Stathopoulos E . Clinical outcome of patients with non-small cell lung cancer receiving front-line chemotherapy according to EGFR and K-RAS mutation status. Lung Cancer. 2009; 69(1):110-5. DOI: 10.1016/j.lungcan.2009.09.010. View

10.

Kwak E, Bang Y, Camidge D, Shaw A, Solomon B, Maki R . Anaplastic lymphoma kinase inhibition in non-small-cell lung cancer. N Engl J Med. 2010; 363(18):1693-703. PMC: 3014291. DOI: 10.1056/NEJMoa1006448. View

11.

Roberts P, Stinchcombe T, Der C, Socinski M . Personalized medicine in non-small-cell lung cancer: is KRAS a useful marker in selecting patients for epidermal growth factor receptor-targeted therapy?. J Clin Oncol. 2010; 28(31):4769-77. DOI: 10.1200/JCO.2009.27.4365. View

12.

Lababede O, Meziane M, Rice T . Seventh edition of the cancer staging manual and stage grouping of lung cancer: quick reference chart and diagrams. Chest. 2011; 139(1):183-9. DOI: 10.1378/chest.10-1099. View

13.

Lozano M, Zulueta J, Echeveste J, Gurpide A, Seijo L, Martin-Algarra S . Assessment of epidermal growth factor receptor and K-ras mutation status in cytological stained smears of non-small cell lung cancer patients: correlation with clinical outcomes. Oncologist. 2011; 16(6):877-85. PMC: 3228207. DOI: 10.1634/theoncologist.2010-0155. View

14.

Fukuoka M, Wu Y, Thongprasert S, Sunpaweravong P, Leong S, Sriuranpong V . Biomarker analyses and final overall survival results from a phase III, randomized, open-label, first-line study of gefitinib versus carboplatin/paclitaxel in clinically selected patients with advanced non-small-cell lung cancer in Asia (IPASS). J Clin Oncol. 2011; 29(21):2866-74. DOI: 10.1200/JCO.2010.33.4235. View

15.

OByrne K, Gatzemeier U, Bondarenko I, Barrios C, Eschbach C, Martens U . Molecular biomarkers in non-small-cell lung cancer: a retrospective analysis of data from the phase 3 FLEX study. Lancet Oncol. 2011; 12(8):795-805. DOI: 10.1016/S1470-2045(11)70189-9. View

16.

Brugger W, Triller N, Blasinska-Morawiec M, Curescu S, Sakalauskas R, Manikhas G . Prospective molecular marker analyses of EGFR and KRAS from a randomized, placebo-controlled study of erlotinib maintenance therapy in advanced non-small-cell lung cancer. J Clin Oncol. 2011; 29(31):4113-20. DOI: 10.1200/JCO.2010.31.8162. View

17.

Thunnissen F, Prinsen C, Hol B, Van der Drift M, Vesin A, Brambilla C . Smoking history and lung carcinoma: KRAS mutation is an early hit in lung adenocarcinoma development. Lung Cancer. 2011; 75(2):156-60. DOI: 10.1016/j.lungcan.2011.07.013. View

18.

Kim H, Shim H, Chung J, Lee Y, Hong Y, Rha S . Distinct clinical features and outcomes in never-smokers with nonsmall cell lung cancer who harbor EGFR or KRAS mutations or ALK rearrangement. Cancer. 2011; 118(3):729-39. DOI: 10.1002/cncr.26311. View

19.

Rosell R, Carcereny E, Gervais R, Vergnenegre A, Massuti B, Felip E . Erlotinib versus standard chemotherapy as first-line treatment for European patients with advanced EGFR mutation-positive non-small-cell lung cancer (EURTAC): a multicentre, open-label, randomised phase 3 trial. Lancet Oncol. 2012; 13(3):239-46. DOI: 10.1016/S1470-2045(11)70393-X. View

20.

Janne P, Shaw A, Pereira J, Jeannin G, Vansteenkiste J, Barrios C . Selumetinib plus docetaxel for KRAS-mutant advanced non-small-cell lung cancer: a randomised, multicentre, placebo-controlled, phase 2 study. Lancet Oncol. 2012; 14(1):38-47. DOI: 10.1016/S1470-2045(12)70489-8. View