The Frequency of Specific KRAS Mutations, and Their Impact on Treatment Choice and Survival, in Patients With Metastatic Colorectal Cancer

Author:

Fernández Montes Ana1ORCID,Alonso Orduña Vicente2,Asensio Martínez Elena3,Rodríguez Salas Nuria4,Torres Esperanza5,Cacho Lavín Diego6,Rodríguez Alonso Rosa María7,Falcó Esther8,Oliva Joan Carles9,Cirera Lluis10,García Gómez Jesus1,Pericay Carles11

Affiliation:

1. Servicio de Oncología Médica, Complexo Hospitalario Universitario de Ourense , Calle Ramón Puga Noguerol, Ourense , Spain

2. Servicio de Oncología Médica, Hospital Universitario Miguel Servet, Instituto de Investigacion Sanitaria de Aragon , Paseo Isabel la Católica, Zaragoza , Spain

3. Servicio de Oncología Médica, Hospital General Universitario de Elche , Carrer Almazara, Elche, Alicante , Spain

4. Servicio de Oncología Médica, Hospital Universitario La Paz , Paseo de la Castellana, Madrid , Spain

5. UGC intercentros de Oncología Médica, Hospitales Universitarios Regional y Virgen de la Victoria and Instituto de Investigación Biomédica de Málaga (IBIMA) , Campus de Teatinos, Málaga , Spain

6. Servicio de Oncología Médica, Hospital Universitario Marqués de Valdecilla , Santander, Cantabria , Spain

7. Servicio de Oncología Médica, Hospital Universitario Reina Sofía-Córdoba , Avenida Menéndez Pidal, Córdoba , Spain

8. Servicio de Oncología Médica, Hospital de Son Llàtzer , Carretera de Manacor, Palma de-Mallorca, Illes Balears , Spain

9. Institut d’Investigació I Innovació I3PT, Fundació Parc Taulí, Plaça Taulí , Sabadell, Barcelona , Spain

10. Servicio de Oncología Médica, Hospital Universitario Mútua Terrassa , Plaça del Doctor Robert, Terrassa, Barcelona , Spain

11. Servicio de Oncología Médica, Hospital Universitari Parc Taulí , Plaça Taulí, Sabadell, Barcelona , Spain

Abstract

Abstract Background Patients with metastatic colorectal cancer (mCRC) and KRAS mutations have a poor prognosis, seemingly dependent on the location of the mutation. This multicenter, retrospective, cohort study assessed the frequency and prognostic value of specific KRAS mutation codon locations in mCRC patients, and survival outcomes in relation to treatment. Materials and Methods Data from mCRC patients treated in 10 Spanish hospitals between January 2011 and December 2015 were analyzed. The main objective was to investigate (1) the impact of KRAS mutation location on overall survival (OS), and (2) the effect of targeted treatment plus metastasectomy and primary tumor location on OS in patients with KRAS mutations. Results The KRAS mutation location was known for 337/2002 patients. Of these, 177 patients received chemotherapy only, 155 received bevacizumab plus chemotherapy, and 5 received anti-epidermal growth factor receptor therapy plus chemotherapy; 94 patients underwent surgery. The most frequent KRAS mutation locations were G12A (33.8%), G12D (21.4%), and G12V (21.4%). Compared with other locations, patients with a G12S mutation had the shortest median OS (10.3 [95% CI, 2.5-18.0] months). OS was longer in patients who underwent surgery versus those who did not, with a trend toward prolonged survival with bevacizumab (median OS 26.7 [95% CI, 21.8-31.7] months) versus chemotherapy alone (median OS 23.2 [95% CI, 19.4-27.0] months). Conclusion These findings confirm that KRAS mutation location may predict survival outcomes in patients with mCRC, and suggest that pre-/post-operative bevacizumab plus metastasectomy provides survival benefits in patients with KRAS mutations.

Funder

Merck

Merck KGaA

Publisher

Oxford University Press (OUP)

Subject

Cancer Research,Oncology

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