KRAS Mutation in Patients with Lung Cancer: A Predictor for Poor Prognosis but Not for EGFR-TKIs or Chemotherapy

Guan, Ji-Lin; Zhong, Wen‐Zhao; An, Shejuan; Yang, Jing; Su, Jian; Chen, Zhihong; Yan, Hong‐Hong; Chen, Zhiyong; Huang, Zhimin; Zhang, Xuchao; Nie, Qiang; Wu, Yi‐Long

doi:10.1245/s10434-012-2754-z

Cited by 80 publications

(98 citation statements)

References 34 publications

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“…without the knowledge of patients' EGFR status) has a predictive role for the second or third-line erlotinib therapy of NSCLC. Importantly, although the role of KRAS mutational analysis in NSCLC treatment is still debated [30][31][32], our data suggest a predictive role of KRAS status for NSCLC patients treated with erlotinib and, furthermore, are in line with subsequently published NCCN NSCLC guidelines which has been incorporated the proposal that "KRAS mutations are associated with intrinsic TKI resistance, and KRAS gene sequencing could be useful for the selection of patients as candidates for TKI therapy" [18].…”

Section: Discussionsupporting

confidence: 68%

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: 68%

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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“…We performed a comprehensive analysis of wellidentified driver genes in the former smokers with NSCLCs, and compared the results with those of the current and never with NSCLCs, demonstrating that the former harbored more EGFR but less KRAS mutations than the current. It has been reported that NSCLCs with EGFR mutations are associated with better outcomes, whereas KRAS mutations, with worse outcome [28,29]. Moreover, lung cancer of EGFR mutation can be treated with EGFR-TKI and prolong PFS overall than treated with chemotherapy, especially in those with exon 19 deletions, never smokers and women [30].…”

Section: Discussionmentioning

confidence: 99%

Former smokers with non‐small‐cell lung cancers: a comprehensive investigation of clinicopathologic characteristics, oncogenic drivers, and prognosis

et al. 2016

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The aim of this present investigation was to evaluate the clinicopathologic characteristics, oncogenic drivers, and prognosis of former smokers with non-smallcell lung cancer (NSCLC), and to compare them with those of the current and never smokers. This investigation was a single-institution retrospective study of 2289 NSCLC patients, who were classified as former, current, or never smokers. A collection was made of the clinicopathological characteristics, spectra of wellidentified driver genes and survival rates. The survival rates were compared using log-rank test, and independent prognostic factors, identified using Cox regression analysis. Of 2289 NSCLC patients, 257 (11.2%) were former smokers; 868 (37.9%), current smokers; and 1164 (50.9%), never smokers. Compared with the current, the former were characterized by older age at diagnosis (64.3y vs. 59.9y; P < 0.001), earlier TNM stage (stage I, 47.9% vs. 39.5%; P = 0.017), fewer solid predominance in adenocarcinomas (16.2% vs. 29.5%; P = 0.005), and more EGFR mutation (33.2% vs. 20.7%; P < 0.001) but less KRAS mutation (6.7% vs. 11.9%, P = 0.041). No statistically significant survival differences were observed between the former and current. However, the light former smokers presented favorable overall survival when compared with the light current and heavy former or current (the light former vs. the heavy former, P = 0.028; the light former vs. the light current, P = 0.048; and the light former vs. the heavy current, P = 0.048). Our findings suggest that the former smokers with NSCLCs can have distinctive clinicopathologic characteristics, oncogenic drivers, and prognosis, and they, especially the light former, can benefit from smoking cessation. Cancer Medicine Open Access 2118

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“…In this study, 6 adenocarcinoma patients with no lepidic component were included, all of whom succumbed to the disease within 2 years of recurrence, whereas patients with tumors with a lepidic component also exhibited poor postrecurrence prognosis. The KRAS mutation was previously reported to be a predictor of poor prognosis, with a worse overall survival of KRAS-mutated patients (25,26). The poor postrecurrence survival may explain the poor prognosis.…”

Section: Discussionmentioning

confidence: 93%

Postrecurrence survival of surgically resected pulmonary adenocarcinoma patients according to EGFR and KRAS mutation status

Ohtaki

Shimizu

Kakegawa

et al. 2013

Molecular and Clinical Oncology

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Abstract. The aim of this study was to investigate the prognosis of pulmonary adenocarcinoma patients following postoperative recurrence, according to epidermal growth factor receptor (EGFR) and Kirsten rat sarcoma 2 viral oncogene homolog (KRAS) gene mutation status and recurrence site. In total 58 adenocarcinoma patients with recurrence following surgical resection were retrospectively evaluated between 2002 and 2011. The patients were divided into groups according to the presence or absence of EGFR and KRAS mutations and the clinicopathological characteristics, recurrence sites and postrecurrence survival were compared. EGFR and KRAS mutations were detected in 26 (45%) and 11 patients (19%), respectively. Initial recurrence was distant in 25 (43%), local in 17 (29%) and both distant and local in 16 cases (28%). In EGFR-mutant (EGFR+) cases, bilateral/contralateral lung recurrence was a frequent finding. EGFR+ cases exhibited significantly better outcomes compared to KRAS+ and EGFR-KRAS-(wild-type) cases. The 2-year post-recurrence survival rates were 81, 18 and 47% in EGFR+, KRAS+ and wild-type cases, respectively. The patients with distant organ recurrence exhibited significantly worse survival compared with those without distant recurrence in wild-type, but not in the EGFR+ cases or the entire cohort. Multivariate analysis revealed that EGFR mutations and a number of recurrent lesions were the only statistically significant independent predictors of postrecurrence prognosis. Our results indicated distinct survival differences in recurrent adenocarcinoma patients according to driver mutations. Patients with EGFR-mutated tumors exhibited increased survival, regardless of recurrence at distant sites, whereas patients with KRAS-mutated adenocarcinoma exhibited poor outcome following postoperative recurrence. Therefore, the assessment of driver mutations is essential for predicting postrecurrence survival following surgical resection.

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KRAS Mutation in Patients with Lung Cancer: A Predictor for Poor Prognosis but Not for EGFR-TKIs or Chemotherapy

Abstract: KRAS mutation is a poor prognosis factor, but it is not an independent predictor of response to EGFR-TKI or chemotherapy in patients with lung cancer.

Cited by 80 publications

References 34 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)

Former smokers with non‐small‐cell lung cancers: a comprehensive investigation of clinicopathologic characteristics, oncogenic drivers, and prognosis

Postrecurrence survival of surgically resected pulmonary adenocarcinoma patients according to EGFR and KRAS mutation status

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