title: Role of KRAS-LCS6 polymorphism in advanced NSCLC patients treated with erlotinib or docetaxel in second line treatment (TAILOR).
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.
authors.affiliation: Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
authors.forename: Monica
authors.initials: M
authors.lastname: Ganzinelli
authors.affiliation: Oncology Department, IRCCS - Istituto di Ricerche Farmacologiche Mario Negri, Italy.
authors.forename: Eliana
authors.initials: E
authors.lastname: Rulli
authors.affiliation: Oncology Department, IRCCS - Istituto di Ricerche Farmacologiche Mario Negri, Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Caiola
authors.affiliation: Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
authors.forename: Marina Chiara
authors.initials: MC
authors.lastname: Garassino
authors.affiliation: Oncology Department, IRCCS - Istituto di Ricerche Farmacologiche Mario Negri, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Broggini
authors.affiliation: Oncology Department, IRCCS - Istituto di Ricerche Farmacologiche Mario Negri, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Copreni
authors.affiliation: Oncology Department, Ospedale Fatebenefratelli e Oftalmico, Milan, Italy.
authors.forename: Sheila
authors.initials: S
authors.lastname: Piva
authors.affiliation: Medical Oncology Department, Policlinico Umberto I Rome, Italy.
authors.forename: Flavia
authors.initials: F
authors.lastname: Longo
authors.affiliation: Oncology Department, Papa Giovanni XXIII Hospital, Bergamo, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Labianca
authors.affiliation: Medical Oncology, Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, Milano, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Bareggi
authors.affiliation: Medical Oncology Department, Ospedale Belcolle, Viterbo, Italy.
authors.forename: Maria Agnese
authors.initials: MA
authors.lastname: Fabbri
authors.affiliation: Medical Oncology Department, San Giovanni e Addolorata Hospital, Rome, Italy.
authors.forename: Olga
authors.initials: O
authors.lastname: Martelli
authors.affiliation: Oncology Department, Azienda Ospedaliera Desio e Vimercate, Vimercate, Italy.
authors.forename: Daniele
authors.initials: D
authors.lastname: Fagnani
authors.affiliation: San Carlo Borromeo Hospital, Milano, Italy.
authors.forename: Maria Cristina
authors.initials: MC
authors.lastname: Locatelli
authors.affiliation: Valtellina e Valchiavenna Hospital, Sondrio, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Bertolini
authors.affiliation: Valtellina e Valchiavenna Hospital, Sondalo, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Valmadre
authors.affiliation: San Pietro Hospital, Roma, Italy.
authors.forename: Ida
authors.initials: I
authors.lastname: Pavese
authors.affiliation: Legnano Hospital, Legnano, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Calcagno
authors.affiliation: Azienda Ospedaliera Universitaria, Sassari, Italy.
authors.forename: Maria Giuseppa
authors.initials: MG
authors.lastname: Sarobba
authors.affiliation: Oncology Department, IRCCS - Istituto di Ricerche Farmacologiche Mario Negri, Italy.
authors.forename: Mirko
authors.initials: M
authors.lastname: Marabese
mesh_terms: D020413:3' Untranslated Regions; D000368:Aged; D000483:Alleles; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D018572:Disease-Free Survival; D000077143:Docetaxel; D000069347:Erlotinib Hydrochloride / Q000627:therapeutic use*; D005260:Female; D005838:Genotype; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D008297:Male; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D016016:Proportional Hazards Models; D043823:Taxoids / Q000627:therapeutic use*; D018631:ras Proteins / Q000235:genetics*
chemical_list: D020413:3' Untranslated Regions; D035683:MicroRNAs; D043823:Taxoids; D000077143:Docetaxel; D000069347:Erlotinib Hydrochloride; D018631:ras Proteins