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Randomized Controlled Trial
. 2015 Nov 17:5:16331.
doi: 10.1038/srep16331.

Role of KRAS-LCS6 polymorphism in advanced NSCLC patients treated with erlotinib or docetaxel in second line treatment (TAILOR)

Monica Ganzinelli  1 , Eliana Rulli  2 , Elisa Caiola  2 , Marina Chiara Garassino  1 , Massimo Broggini  2 , Elena Copreni  2 , Sheila Piva  3 , Flavia Longo  4 , Roberto Labianca  5 , Claudia Bareggi  6 , Maria Agnese Fabbri  7 , Olga Martelli  8 , Daniele Fagnani  9 , Maria Cristina Locatelli  10 , Alessandro Bertolini  11 , Giuseppe Valmadre  12 , Ida Pavese  13 , Anna Calcagno  14 , Maria Giuseppa Sarobba  15 , Mirko Marabese  2
Affiliations
Randomized Controlled Trial

Role of KRAS-LCS6 polymorphism in advanced NSCLC patients treated with erlotinib or docetaxel in second line treatment (TAILOR)

Monica Ganzinelli et al. Sci Rep. .

Abstract

MicroRNAs were described to target mRNA and regulate the transcription of genes involved in processes de-regulated in tumorigenesis, such as proliferation, differentiation and survival. In particular, the miRNA let-7 has been suggested to regulate the expression of the KRAS gene, a common mutated gene in non-small cell lung cancer (NSCLC), through a let-7 complementary site (LCS) in 3'UTR of KRAS mRNA. We have reported the analysis performed on the role of the polymorphism located in the KRAS-LCS (rs61764370) which is involved in the disruption of the let-7 complementary site in NSCLC patients enrolled within the TAILOR trial, a randomised trial comparing erlotinib versus docetaxel in second line treatment. In our cohort of patients, KRAS-LCS6 polymorphism did not have any impact on both overall survival (OS) and progression free survival (PFS) and was not associated with any patient's baseline characteristics included in the study. Overall, patients had a better prognosis when treated with docetaxel instead of erlotinib for both OS and PFS. Considering KRAS-LCS6 status, the TG/GG patients had a benefit from docetaxel treatment (HR(docetaxel vs erlotinib) = 0.35, 95% CI 0.15-0.79, p = 0.011) compared with the TT patients (HR(docetaxel vs erlotinib) = 0.72, 95% CI 0.52-1.01, p = 0.056) in terms of PFS.

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Figures

Figure 1
Figure 1
Kaplan-Meier curves for OS (a) and PFS (b) according to KRAS-LCS6 genotype.
Figure 2
Figure 2
Kaplan-Meier curves reporting OS (upper panels) and PFS (lower panels) in TT (panels (A,C) and TG/GG (panels (B,D) patients according to treatment arm.
Figure 3
Figure 3
Forest Plots showing the predictive role of KRAS-LCS6 polymorphism.
Figure 4
Figure 4
Kaplan-Meier curves reporting OS (upper panels) and PFS (lower panels) by KRAS status and genotypes.
See this image and copyright information in PMC

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