Manuel Benavides1, Auxiliadora Gómez-España2, Pilar García-Alfonso3, Cristina García González4, Jose María Viéitez5, Fernando Rivera6, María José Safont7, Albert Abad8, Javier Sastre9, Manuel Valladares-Ayerbes10, Alfredo Carrato11, Encarnación González-Flores12, Luis Robles13, Antonieta Salud14, Vicente Alonso-Orduña15, Clara Montagut16, Elena Asensio17, Eduardo Díaz-Rubio9, Enrique Aranda2. 1. UGC Intercentros de Oncología Médica, Hospitales Universitarios Regional y Virgen de la Victoria, IBIMA, Málaga, Spain. Electronic address: manubenavidesor@gmail.com. 2. Department of Medical Oncology, IMIBIC, Universidad de Córdoba, CIBERONC, Instituto de Salud Carlos III, Hospital Universitario Reina Sofía, Córdoba, Spain. 3. Department of Medical Oncology, Hospital Universitario Gregorio Marañón, Madrid, Spain. 4. UGC Intercentros de Oncología Médica, Hospitales Universitarios Regional y Virgen de la Victoria, IBIMA, Málaga, Spain. 5. Department of Medical Oncology, Hospital Universitario Central de Asturias, Oviedo, Spain. 6. Department of Medical Oncology, University Hospital Marqués de Valdecilla, IDIVAL, Santander, Spain. 7. Department of Medical Oncology, Hospital General Universitario Valencia, Universidad de Valencia, CIBERONC, Valencia, Spain. 8. Department of Medical Oncology, Instituto Oncológico Dr. Rosell, Barcelona, Spain. 9. Department of Medical Oncology, Hospital Clínico San Carlos, Instituto de Investigación Hospital Clínico San Carlos (IdISSC), University Complutense, CIBERONC, Madrid, Spain. 10. Department of Medical Oncology, Hospital Virgen del Rocío, IBIS, Sevilla, Spain. 11. Department of Medical Oncology, IRYCIS, CIBERONC, Alcalá University, Hospital Universitario Ramón y Cajal, Madrid, Spain. 12. Department of Medical Oncology, Hospital Virgen de las Nieves, Granada, Spain. 13. Department of Medical Oncology, Hospital 12 de Octubre, Madrid, Spain. 14. Department of Medical Oncology, Hospital de Lleida Arnau de Vilanova, Lérida, Spain. 15. Department of Medical Oncology, Hospital Universitario Miguel Servet, Instituto de Investigación Sanitaria de Aragón (IISA), Zaragoza, Spain. 16. Department of Medical Oncology, Hospital del Mar Medical Research Institute, CIBERONC, Barcelona, Spain. 17. Department of Medical Oncology, Hospital General Universitario de Elche, Alicante, Spain.
Abstract
INTRODUCTION: Retrospective studies and meta-analyses suggest that upfront primary tumour resection (UPTR) confers a survival benefit in patients with asymptomatic unresectable metastatic colorectal cancer (mCRC) undergoing chemotherapy, however a consensus of its role in routine clinical practice in the current era of targeted therapies is lacking. This retrospective study aimed to analyse the survival benefit of UPTR in terms of tumour location and mutational status, in patients with synchronous mCRC receiving chemotherapy and targeted therapy. PATIENTS AND METHODS: Survival was analysed in a pooled cohort of synchronous mCRC patients treated with a first-line anti-VEGF or anti-EGFR inhibitor in seven trials of the Spanish TTD group, according to UPTR, tumour-sidedness and mutational profiling. RESULTS: Of 1334 eligible patients, 642 (48%) had undergone UPTR. UPTR was associated with significantly longer overall survival (OS; 25.0 vs 20.3 months; HR 1.30, 95%CI 1.15-1.48; p < 0.0001). UPTR was associated with significant OS benefit in both left-sided (HR 1.38, 95%CI 1.13-1.69; p = 0.002) and right-sided (HR 1.39, 95%CI 1.00-1.94; p = 0.049) tumours, RASwt (HR 1.29, 95%CI 1.05-1.60; p = 0.016) and BRAFwt (HR 1.49, 95%CI 1.21-1.84; p = 0.0002) tumours, and treatment with anti-EGFRs (HR 1.47, 95%CI 1.13-1.92; p = 0.004) and anti-VEGFs (HR 1.25, 95%CI 1.08-1.44; p = 0.003). Multivariate analysis identified number of metastatic sites, RAS status, primary tumour location and UPTR as independent prognostic factors for OS. CONCLUSION: Considering the selection bias inherent to this study, our results support UPTR before first-line anti-EGFR or anti-VEGF targeted therapy in right and left-sided asymptomatic unresectable synchronous mCRC patients. RAS/BRAF mutational status may also influence UPTR function.
INTRODUCTION: Retrospective studies and meta-analyses suggest that upfront primary tumour resection (UPTR) confers a survival benefit in patients with asymptomatic unresectable metastatic colorectal cancer (mCRC) undergoing chemotherapy, however a consensus of its role in routine clinical practice in the current era of targeted therapies is lacking. This retrospective study aimed to analyse the survival benefit of UPTR in terms of tumour location and mutational status, in patients with synchronous mCRC receiving chemotherapy and targeted therapy. PATIENTS AND METHODS: Survival was analysed in a pooled cohort of synchronous mCRC patients treated with a first-line anti-VEGF or anti-EGFR inhibitor in seven trials of the Spanish TTD group, according to UPTR, tumour-sidedness and mutational profiling. RESULTS: Of 1334 eligible patients, 642 (48%) had undergone UPTR. UPTR was associated with significantly longer overall survival (OS; 25.0 vs 20.3 months; HR 1.30, 95%CI 1.15-1.48; p < 0.0001). UPTR was associated with significant OS benefit in both left-sided (HR 1.38, 95%CI 1.13-1.69; p = 0.002) and right-sided (HR 1.39, 95%CI 1.00-1.94; p = 0.049) tumours, RASwt (HR 1.29, 95%CI 1.05-1.60; p = 0.016) and BRAFwt (HR 1.49, 95%CI 1.21-1.84; p = 0.0002) tumours, and treatment with anti-EGFRs (HR 1.47, 95%CI 1.13-1.92; p = 0.004) and anti-VEGFs (HR 1.25, 95%CI 1.08-1.44; p = 0.003). Multivariate analysis identified number of metastatic sites, RAS status, primary tumour location and UPTR as independent prognostic factors for OS. CONCLUSION: Considering the selection bias inherent to this study, our results support UPTR before first-line anti-EGFR or anti-VEGF targeted therapy in right and left-sided asymptomatic unresectable synchronous mCRC patients. RAS/BRAF mutational status may also influence UPTR function.