Giulio Metro1, Rita Chiari2, Chiara Bennati2, Matteo Cenci2, Biagio Ricciuti2, Francesco Puma3, Antonella Flacco2, Alberto Rebonato4, Diana Giannarelli5, Vienna Ludovini2, Guido Bellezza6, Piero Ferolla2, Vincenzo Minotti2, Lucio Crinò2. 1. Medical Oncology, Santa Maria della Misericordia Hospital, Azienda Ospedaliera di Perugia, Perugia, Italy. Electronic address: giulio.metro@yahoo.com. 2. Medical Oncology, Santa Maria della Misericordia Hospital, Azienda Ospedaliera di Perugia, Perugia, Italy. 3. Department of Thoracic Surgery, Santa Maria della Misericordia Hospital, Azienda Ospedaliera di Perugia, Perugia, Italy. 4. Department of Diagnostic Imaging, Santa Maria della Misericordia Hospital, Azienda Ospedaliera di Perugia, Perugia, Italy. 5. Biostatistics and Data Management Core, Regina Elena Cancer Institute, Rome, Italy. 6. Department of Pathology, Santa Maria della Misericordia Hospital, Azienda Ospedaliera di Perugia, Perugia, Italy.
Abstract
BACKGROUND: We hypothesized that KRAS mutations function as a marker of poor sensitivity to first-line platinum-based chemotherapy in patients with advanced nonsquamous EGFR wild-type (WT) non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Consecutive advanced nonsquamous EGFR WT NSCLCs treated at the Medical Oncology of Perugia with simultaneous assessment of KRAS mutation status were eligible. Anaplastic lymphoma kinase (ALK) gene status was known in roughly half of the patients who had KRAS WT. RESULTS: Two hundred four patients were included. Among them, the 77 individuals carrying a KRAS-mutant phenotype experienced a significantly inferior outcome in terms of response rate (P = .04), disease control rate (P = .05), and progression-free survival (PFS) (P = .05) compared with the EGFR WT/KRAS WT population. The association between KRAS mutation and shorter PFS remained statistically significant at multivariate analysis (hazard ratio [HR], 1.45). In addition, patients with KRAS mutations reported a significantly shorter overall survival (OS) compared with patients with EGFR WT/KRAS WT/ALK negativity (n = 64) (P = .02). Among patients with KRAS mutations, those harboring a mutation at codon 13 (n = 12) performed worse than those with a mutation at codon 12 (n = 62) in terms of both PFS and OS (P = .09 for both). CONCLUSION: KRAS mutation appears to negatively affect sensitivity to first-line platinum-based chemotherapy in patients with advanced nonsquamous EGFR WT NSCLC. Studies on larger case series are needed to address differences in clinical outcome according to the type of mutation.
BACKGROUND: We hypothesized that KRAS mutations function as a marker of poor sensitivity to first-line platinum-based chemotherapy in patients with advanced nonsquamous EGFR wild-type (WT) non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Consecutive advanced nonsquamous EGFRWT NSCLCs treated at the Medical Oncology of Perugia with simultaneous assessment of KRAS mutation status were eligible. Anaplastic lymphoma kinase (ALK) gene status was known in roughly half of the patients who had KRAS WT. RESULTS: Two hundred four patients were included. Among them, the 77 individuals carrying a KRAS-mutant phenotype experienced a significantly inferior outcome in terms of response rate (P = .04), disease control rate (P = .05), and progression-free survival (PFS) (P = .05) compared with the EGFR WT/KRAS WT population. The association between KRAS mutation and shorter PFS remained statistically significant at multivariate analysis (hazard ratio [HR], 1.45). In addition, patients with KRAS mutations reported a significantly shorter overall survival (OS) compared with patients with EGFR WT/KRAS WT/ALK negativity (n = 64) (P = .02). Among patients with KRAS mutations, those harboring a mutation at codon 13 (n = 12) performed worse than those with a mutation at codon 12 (n = 62) in terms of both PFS and OS (P = .09 for both). CONCLUSION:KRAS mutation appears to negatively affect sensitivity to first-line platinum-based chemotherapy in patients with advanced nonsquamous EGFR WT NSCLC. Studies on larger case series are needed to address differences in clinical outcome according to the type of mutation.
Authors: B Ricciuti; M Brambilla; A Cortellini; A De Giglio; C Ficorella; A Sidoni; G Bellezza; L Crinò; V Ludovini; S Baglivo; G Metro; R Chiari Journal: Clin Transl Oncol Date: 2019-07-22 Impact factor: 3.405
Authors: Miguel A Villalona-Calero; Elaine Lam; Gregory A Otterson; Weiqiang Zhao; Matthew Timmons; Deepa Subramaniam; Erinn M Hade; George M Gill; Matthew Coffey; Giovanni Selvaggi; Erin Bertino; Bo Chao; Michael V Knopp Journal: Cancer Date: 2015-12-28 Impact factor: 6.860