Subtype-specific KRAS mutations in advanced lung adenocarcinoma: A retrospective study of patients treated with platinum-based chemotherapy

• Published in: European journal of cancer (1990) 2014-07, Vol.50 (10), p.1819-1828
• Main Authors: Cserepes, Mihaly, Ostoros, Gyula, Lohinai, Zoltan, Raso, Erzsebet, Barbai, Tamas, Timar, Jozsef, Rozsas, Anita, Moldvay, Judit, Kovalszky, Ilona, Fabian, Katalin, Gyulai, Marton, Ghanim, Bahil, Laszlo, Viktoria, Klikovits, Thomas, Hoda, Mir Alireza, Grusch, Michael, Berger, Walter, Klepetko, Walter, Hegedus, Balazs, Dome, Balazs
• Format: Article
• Language: English
• Subjects: Adenocarcinoma - drug therapy; Adenocarcinoma - ethnology; Adenocarcinoma - genetics; Adenocarcinoma - mortality; Adenocarcinoma - pathology; Adenocarcinoma of Lung; Adult; Advanced-stage lung adenocarcinoma; Aged; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biological and medical sciences; Carboplatin - administration & dosage; Chi-Square Distribution; Cisplatin - administration & dosage; Disease-Free Survival; DNA Mutational Analysis; European Continental Ancestry Group - genetics; Female; Genetic Predisposition to Disease; Hematology, Oncology and Palliative Medicine; Humans; Hungary - epidemiology; Kaplan-Meier Estimate; KRAS mutation; Lung Neoplasms - drug therapy; Lung Neoplasms - ethnology; Lung Neoplasms - genetics; Lung Neoplasms - mortality; Lung Neoplasms - pathology; Male; Medical sciences; Middle Aged; Multiple tumors. Solid tumors. Tumors in childhood (general aspects); Multivariate Analysis; Mutation; Neoplasm Staging; Non-small cell lung cancer; Patient Selection; Pharmacology. Drug treatments; Phenotype; Platinum-based chemotherapy; Pneumology; Proportional Hazards Models; Proto-Oncogene Proteins - genetics; Proto-Oncogene Proteins p21(ras); ras Proteins - genetics; Retrospective Studies; Risk Factors; Smoking - adverse effects; Smoking - ethnology; Time Factors; Treatment Outcome; Tumors; Tumors of the respiratory system and mediastinum
• ISSN: 0959-8049; 1879-0852
• DOI: 10.1016/j.ejca.2014.04.001

Abstract Background Platinum-based chemotherapy is the most common treatment in advanced-stage lung adenocarcinoma. Because the clinical significance of KRAS mutational status in this setting has not yet been clearly determined, a mutation subtype-specific analysis was performed in the so far largest cohort of Caucasian patients with KRAS mutant advanced-stage lung adenocarcinoma treated with platinum-based chemotherapy. Methods 505 Caucasian stage III–IV lung adenocarcinoma patients with known amino acid substitution-specific KRAS mutational status and treated with platinum-based chemotherapy were included. The correlations of subtype-specific KRAS mutations with smoking status, progression-free and overall survival (PFS and OS, respectively) and therapeutic response were analysed. Results Among 338 KRAS wild-type, 147 codon 12 mutant and 20 codon 13 mutant patients, there were no mutation-related significant differences in PFS or OS ( P values were 0.534 and 0.917, respectively). Eastern Cooperative Oncology Group (ECOG) status and clinical stage were significant independent prognostic factors. KRAS mutation showed a significant correlation with smoking status ( P = 0.018). Importantly, however, G12V KRAS mutant patients were significantly more frequent among never-smokers than all other codon 12 KRAS mutant (G12x) subtypes ( P = 0.016). Furthermore, this subgroup tended to have a higher response rate (66% versus 47%; P = 0.077). A modestly longer median PFS was also found in the G12V mutant cohort (233 days; versus 175 days in the G12x group; P = 0.145). Conclusions While KRAS mutation status per se is neither prognostic nor predictive in stage III–IV lung adenocarcinoma, subtype-specific analysis may indeed identify clinically relevant subgroups of patients that may ultimately influence treatment decisions.