KRAS Mutations in Lung Cancer

Karachaliou, Niki; Mayo, Clara; Costa, Carlota; Magrí, Ignacio; Giménez‐Capitán, Ana; Molina-Vila, Miguel Ángel; Rosell, Rafael

doi:10.1016/j.cllc.2012.09.007

Cited by 190 publications

(155 citation statements)

References 82 publications

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“…In part because of ethical objections our study did not involve a cohort of patients with KRASmutated NSCLCs. However, the relatively high median PFS and OS data observed in our study do not only suggest that second or thirdline erlotinib therapy confers significant benefit to patients with advanced stage KRAS WT lung adenocarcinoma but our findings also support the well-known but still ambiguous concept [35][36][37][38] that KRAS mutation analysis might predict treatment non-response to EGFR TKI therapy in NSCLC.…”

Section: Discussionsupporting

confidence: 77%

“…In conclusion, the clinical value of KRAS mutation to predict therapeutic response to EGFR-TKI treatment in NSCLC remains ambiguous and thus EGFR mutational status analysis is currently the preferred test in this setting [35][36][37][38]. In part because of ethical objections our study did not involve a cohort of patients with KRASmutated NSCLCs.…”

Section: Discussionmentioning

confidence: 99%

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Effectiveness of erlotinib treatment in advanced KRAS mutation-negative lung adenocarcinoma patients: Results of a multicenter observational cohort study (MOTIVATE)

et al. 2014

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a b s t r a c tObjectives: Erlotinib is an epidermal growth factor receptor tyrosine-kinase inhibitor (EGFR-TKI), used for the treatment of non-small cell lung cancer. As the clinical significance of KRAS mutational status has not yet been clearly determined in this setting, our aim was to investigate the efficacy of erlotinib in advanced KRAS mutation-negative lung adenocarcinoma patients. Materials and methods:MOTIVATE is an open-label, multicenter, observational trial with Tarceva ® (erlotinib) monotherapy. Enrolled patients with advanced (stage IIIB/IV) KRAS wild type (WT) lung adenocarcinoma refractory to one or two courses of prior chemotherapy were treated with erlotinib at 150 mg/day. The primary endpoint was progression-free survival (PFS). Secondary endpoints were overall survival (OS) and best tumor response rate (RR). Results and conclusion: In total, 327 patients were included. Median PFS and OS were 3.3 and 14.4 months, respectively. Three patients (1.2%) had complete response, 51 patients (20.2%) had partial response and 123 patients (48.8%) had SD.Significantly longer median PFS and OS were observed in Eastern Oncology Cooperative Group Performance Status (ECOG PS) 0-1 patients, as compared to ECOG PS 2-3 patients. The longest median OS (20.5 months) was found in patients with ECOG PS 0-1 who received erlotinib as a second-line therapy. There was no difference in median OS in cohorts stratified to disease stage and smoking status. Female patients had both longer median PFS and OS. Disease control rate was 70.2%.Our results suggest that erlotinib represents a valid treatment option for patients with KRAS WT lung adenocarcinoma and, moreover, that KRAS mutation analysis could help to identify clinically relevant subgroups of NSCLC patients that may benefit from EGFR-TKI therapy.

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Section: Discussionsupporting

confidence: 77%

Section: Discussionmentioning

confidence: 99%

Effectiveness of erlotinib treatment in advanced KRAS mutation-negative lung adenocarcinoma patients: Results of a multicenter observational cohort study (MOTIVATE)

et al. 2014

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“…Studies of some researchers have revealed that proper expression of EGFR in epithelium-derived tumor cells (breast cancer or NSCLC, etc.) not only regulate cell proliferation, but also has critical impact on the development of tumors, formation of vessels as well as metastasis and spreading of tumor cells, whereas over-expression of EGFR is insensitive to chemotherapy and radiotherapy, which can easily bring about distant metastasis and poor prognosis Karachaliou et al, 2013;Lopez-Rios et al, 2013). Results of other studies have indicated that EGFR is over expressed in 40~80% of NSCLC patients with poor prognosis but it can be activated by selective inhibition of targeted therapy on the activity of tyrosine kinase (TK) to inhabit proliferation, invasion and metastasis of tumor cells and strengthen chemotherapeutic effect Chen et al, 2013).…”

Section: Discussionmentioning

confidence: 99%

Serum CEA Level Change and Its Significance Before and after Gefitinib Therapy on Patients with Advanced Non-small Cell Lung Cancer

Qin

Qu²,

Liu³

et al. 2013

Asian Pacific Journal of Cancer Prevention

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Objective: The aim of this study was to explore change and significance of serum carcino-embryonic antigen (CEA) before and after gefitinib therapy in patients with advanced non-small-cell lung cancer (NSCLC). Methods: Forty patients with advanced NSCLCs in Ⅲ~Ⅳ stages were selected as study objects given gefitinib therapy combined with routine local radiotherapy until tumor progression or intolerable toxicity. After treatment, all patients were divided into control and non-control groups according to the results of evaluation based on RECIST 1.1 (Response Evaluation Criteria in Solid Tumors in 2009). Peripheral fasting blood from all patients was collected in the early morning and serum CEA was assessed by electro-chemiluminescence immunoassay (ECLIA) before and after treatment. Before treatment, patients were divided into high CEA group (CEA level > 50 ng/mL) and low CEA group (CEA level ≤ 50 ng/mL). Adverse reactions were noted and progression-free survival (PFS) in both groups was recorded after long-term follow-up that ended in December, 2012. Results: There was no difference between control and non-control groups in CEA level before treatment (P>0.05), whereas serum CEA decreased more markedly lower in the control group after treatment (P<0.01). All patients were divided into high CEA group (26) and low CEA group (14) according to serum CEA level. There was no statistically significant difference between two groups in adverse reactions (P>0.05) but the rate in former group was lower. Additionally, survival rates at 9 and 12 months in high CEA group were clearly higher than in the low CEA group (P<0.01). Conclusions: Serum CEA level can serve as a biochemical index to evaluate the prognosis with gefitinib treatment for NSCLC.

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“…The majority of KRAS-mutant cases in NSCLC present single point mutations at codon 12, while mutations in others positions are relatively rare (in codons 13 and 61) (7). Within codon 12, the most frequent point mutations are G12C (42%), G12V (21%), G12D (17%) and G12A (7%) (8). Current or former smokers have a significantly higher frequency of KRAS mutations than never smokers (9) and it is possible to identify the primary mutagenic signature of DNA damage by tobacco smoke.…”

mentioning

confidence: 93%

“…Some data show that adjuvant chemotherapy is unlikely to benefit NSCLC patients harboring KRAS mutations. Nevertheless, in a recent study KRAS codon 13 mutations appeared to be deleterious and the patients had significantly worse OS with adjuvant chemotherapy (6,8).…”

Section: Kras Mutations As a Predictive Factor Of Resistancementioning

confidence: 99%

KRAS mutations in the circulating free DNA (cfDNA) of non-small cell lung cancer (NSCLC) patients

Garzón¹,

Villatoro²,

Teixidó³

et al. 2016

Transl. Lung Cancer Res.

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KRAS Mutations in Lung Cancer

Cited by 190 publications

References 82 publications

Effectiveness of erlotinib treatment in advanced KRAS mutation-negative lung adenocarcinoma patients: Results of a multicenter observational cohort study (MOTIVATE)

Effectiveness of erlotinib treatment in advanced KRAS mutation-negative lung adenocarcinoma patients: Results of a multicenter observational cohort study (MOTIVATE)

Serum CEA Level Change and Its Significance Before and after Gefitinib Therapy on Patients with Advanced Non-small Cell Lung Cancer

KRAS mutations in the circulating free DNA (cfDNA) of non-small cell lung cancer (NSCLC) patients

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