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

Mihaly Cserepes, G. Ostoros, Zoltan Lohinai, E. Rásó, Tamas Barbai, J. Tímár, Anita Rozsas, Judit Moldvay, I. Kovalszky, Katalin Fabian, Marton Gyulai, Bahil Ghanim, Viktoria Laszlo, Thomas Klikovits, Mir Alireza Hoda, Michael Grusch, Walter Berger, Walter Klepetko, B. Hegedűs, B. Döme

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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.

Original languageEnglish
Pages (from-to)1819-1828
Number of pages10
JournalEuropean Journal of Cancer
Volume50
Issue number10
DOIs
Publication statusPublished - 2014

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Platinum
Retrospective Studies
Drug Therapy
Mutation
Codon
Smoking
Amino Acid Substitution
Disease-Free Survival
Therapeutics
Adenocarcinoma of lung

Keywords

  • Advanced-stage lung adenocarcinoma
  • KRAS mutation
  • Non-small cell lung cancer
  • Platinum-based chemotherapy

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Subtype-specific KRAS mutations in advanced lung adenocarcinoma : A retrospective study of patients treated with platinum-based chemotherapy. / Cserepes, Mihaly; Ostoros, G.; Lohinai, Zoltan; Rásó, E.; Barbai, Tamas; Tímár, J.; Rozsas, Anita; Moldvay, Judit; Kovalszky, I.; Fabian, Katalin; Gyulai, Marton; Ghanim, Bahil; Laszlo, Viktoria; Klikovits, Thomas; Hoda, Mir Alireza; Grusch, Michael; Berger, Walter; Klepetko, Walter; Hegedűs, B.; Döme, B.

In: European Journal of Cancer, Vol. 50, No. 10, 2014, p. 1819-1828.

Research output: Contribution to journalArticle

Cserepes, M, Ostoros, G, Lohinai, Z, Rásó, E, Barbai, T, Tímár, J, Rozsas, A, Moldvay, J, Kovalszky, I, Fabian, K, Gyulai, M, Ghanim, B, Laszlo, V, Klikovits, T, Hoda, MA, Grusch, M, Berger, W, Klepetko, W, Hegedűs, B & Döme, B 2014, 'Subtype-specific KRAS mutations in advanced lung adenocarcinoma: A retrospective study of patients treated with platinum-based chemotherapy', European Journal of Cancer, vol. 50, no. 10, pp. 1819-1828. https://doi.org/10.1016/j.ejca.2014.04.001
Cserepes, Mihaly ; Ostoros, G. ; Lohinai, Zoltan ; Rásó, E. ; Barbai, Tamas ; Tímár, J. ; Rozsas, Anita ; Moldvay, Judit ; Kovalszky, I. ; Fabian, Katalin ; Gyulai, Marton ; Ghanim, Bahil ; Laszlo, Viktoria ; Klikovits, Thomas ; Hoda, Mir Alireza ; Grusch, Michael ; Berger, Walter ; Klepetko, Walter ; Hegedűs, B. ; Döme, B. / Subtype-specific KRAS mutations in advanced lung adenocarcinoma : A retrospective study of patients treated with platinum-based chemotherapy. In: European Journal of Cancer. 2014 ; Vol. 50, No. 10. pp. 1819-1828.
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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.",
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TY - JOUR

T1 - Subtype-specific KRAS mutations in advanced lung adenocarcinoma

T2 - A retrospective study of patients treated with platinum-based chemotherapy

AU - Cserepes, Mihaly

AU - Ostoros, G.

AU - Lohinai, Zoltan

AU - Rásó, E.

AU - Barbai, Tamas

AU - Tímár, J.

AU - Rozsas, Anita

AU - Moldvay, Judit

AU - Kovalszky, I.

AU - Fabian, Katalin

AU - Gyulai, Marton

AU - Ghanim, Bahil

AU - Laszlo, Viktoria

AU - Klikovits, Thomas

AU - Hoda, Mir Alireza

AU - Grusch, Michael

AU - Berger, Walter

AU - Klepetko, Walter

AU - Hegedűs, B.

AU - Döme, B.

PY - 2014

Y1 - 2014

N2 - 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.

AB - 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.

KW - Advanced-stage lung adenocarcinoma

KW - KRAS mutation

KW - Non-small cell lung cancer

KW - Platinum-based chemotherapy

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