C Cremolini1, C Antoniotti2, S Lonardi3, F Bergamo3, E Cortesi4, G Tomasello5, R Moretto2, M Ronzoni6, P Racca7, F Loupakis8, A Zaniboni9, G Tonini10, A Buonadonna11, F Marmorino2, G Allegrini12, C Granetto13, G Masi2, V Zagonel3, E Sensi14, G Fontanini15, L Boni16, A Falcone2. 1. Unit of Medical Oncology 2, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy; Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy. Electronic address: chiaracremolini@gmail.com. 2. Unit of Medical Oncology 2, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy; Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy. 3. Unit of Medical Oncology 1, Department of Clinical and Experimental Oncology, Istituto Oncologico Veneto IRCCS, Padua, Italy. 4. Department of Medical Oncology, University of Rome La Sapienza, Rome, Italy. 5. Oncology Department, ASST Ospedale di Cremona, Cremona, Italy. 6. Department of Oncology, "San Raffaele" Hospital IRCSS, Milan, Italy. 7. SSD ColoRectal Unit-Department of Medical Oncology, AOU Città della Salute e della Scienza di Torino, Turin, Italy. 8. Unit of Medical Oncology 2, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy; Unit of Medical Oncology 1, Department of Clinical and Experimental Oncology, Istituto Oncologico Veneto IRCCS, Padua, Italy. 9. Department of Medical Oncology, Poliambulanza Foundation, Brescia, Italy. 10. Department of Medical Oncology, University Campus Biomedico, Rome, Italy. 11. Division of Oncology, Centro di Riferimento Oncologico, Aviano, Italy. 12. Unit of Medical Oncology, Hospital Felice Lotti, Azienda Toscana Nord Ovest, Pontedera, Italy. 13. Unit of Medical Oncology, Azienda Sanitaria Ospedaliera Santa Croce e Carle, Cuneo, Italy. 14. Unit of Pathology 3, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy. 15. Department of Surgical, Medical, Molecular Pathology and Critical Area, University of Pisa, Pisa, Italy. 16. Clinical Trials Coordinating Center, Istituto Toscano Tumori, University Hospital Careggi, Florence, Italy.
Abstract
Background: Right-sided metastatic colorectal cancer (mCRC) patients have poor prognosis and achieve limited benefit from first-line doublets plus a targeted agent. In this unplanned analysis of the TRIBE study, we investigated the prognostic and predictive impact of primary tumor sidedness in mCRC patients and the differential impact of the intensification of the chemotherapy in subgroups defined according to both primary tumor sidedness and RAS and BRAF mutational status. Patients and methods: Patients were randomized to receive upfront 5-fluoruracil, leucovorin, and irinotecan (FOLFIRI) plus bevacizumab or 5-fluoruracil, leucovorin, oxaliplatin, and irinotecan (FOLFOXIRI) plus bevacizumab. Tumors were defined as right- or left-sided if they originated from the caecum to the transverse colon or within the splenic flexure and beyond, respectively. Patients with available information about both primary sidedness and RAS and BRAF status were included in the present analysis. Progression-free survival (PFS), overall survival (OS) and RECIST response rate were assessed according to tumor location and RAS and BRAF mutational status. Results: Information about primary sidedness and RAS and BRAF status was available for 358 (70.5%) out of 508 randomized patients. Patients with right-sided tumors (N = 173) presented shorter OS [23.7 versus 31.0 months, HR = 1.42 (95% CI 1.09-1.84), P = 0.010] and a trend toward shorter PFS [10.2 versus 11.5 months, HR = 1.24 (95% CI: 0.98-1.56), P = 0.083] than those with left-sided tumors (N = 185), but these associations were no longer evident when adjusting for RAS and BRAF status. Patients with right-sided tumors achieved more relative benefit from the intensification of the chemotherapy backbone in terms of both PFS (HR = 0.59 versus 0.89, P for interaction = 0.099) and OS (HR = 0.56 versus 0.99, P for interaction = 0.030) and this advantage was independent of their RAS and BRAF status. Conclusions: FOLFOXIRI plus bevacizumab may be regarded as a preferred first-line treatment option for clinically selected patients with right-sided metastatic colorectal cancer irrespective of their RAS and BRAF mutational status. Trial registration: clinicaltrials.gov identifier NCT00719797.
RCT Entities:
Background: Right-sided metastatic colorectal cancer (mCRC) patients have poor prognosis and achieve limited benefit from first-line doublets plus a targeted agent. In this unplanned analysis of the TRIBE study, we investigated the prognostic and predictive impact of primary tumor sidedness in mCRC patients and the differential impact of the intensification of the chemotherapy in subgroups defined according to both primary tumor sidedness and RAS and BRAF mutational status. Patients and methods: Patients were randomized to receive upfront 5-fluoruracil, leucovorin, and irinotecan (FOLFIRI) plus bevacizumab or 5-fluoruracil, leucovorin, oxaliplatin, and irinotecan (FOLFOXIRI) plus bevacizumab. Tumors were defined as right- or left-sided if they originated from the caecum to the transverse colon or within the splenic flexure and beyond, respectively. Patients with available information about both primary sidedness and RAS and BRAF status were included in the present analysis. Progression-free survival (PFS), overall survival (OS) and RECIST response rate were assessed according to tumor location and RAS and BRAF mutational status. Results: Information about primary sidedness and RAS and BRAF status was available for 358 (70.5%) out of 508 randomized patients. Patients with right-sided tumors (N = 173) presented shorter OS [23.7 versus 31.0 months, HR = 1.42 (95% CI 1.09-1.84), P = 0.010] and a trend toward shorter PFS [10.2 versus 11.5 months, HR = 1.24 (95% CI: 0.98-1.56), P = 0.083] than those with left-sided tumors (N = 185), but these associations were no longer evident when adjusting for RAS and BRAF status. Patients with right-sided tumors achieved more relative benefit from the intensification of the chemotherapy backbone in terms of both PFS (HR = 0.59 versus 0.89, P for interaction = 0.099) and OS (HR = 0.56 versus 0.99, P for interaction = 0.030) and this advantage was independent of their RAS and BRAF status. Conclusions: FOLFOXIRI plus bevacizumab may be regarded as a preferred first-line treatment option for clinically selected patients with right-sided metastatic colorectal cancer irrespective of their RAS and BRAF mutational status. Trial registration: clinicaltrials.gov identifier NCT00719797.
Authors: Jane E Rogers; Terri L Woodard; Graciela Mn Gonzalez; Arvind Dasari; Benny Johnson; Van K Morris; Bryan Kee; Eduardo Vilar; Y Nancy You; George J Chang; Brian Bednarski; John M Skibber; Miguel A Rodriguez-Bigas; Cathy Eng Journal: Obstet Med Date: 2021-09-07
Authors: Nelleke P M Brouwer; Dave E W van der Kruijssen; Niek Hugen; Ignace H J T de Hingh; Iris D Nagtegaal; Rob H A Verhoeven; Miriam Koopman; Johannes H W de Wilt Journal: Ann Surg Oncol Date: 2019-12-02 Impact factor: 5.344
Authors: Mohammad Adileh; Jonathan B Yuval; Henry S Walch; Walid K Chatila; Rona Yaeger; Julio Garcia-Aguilar; Nikolaus Schultz; Philip B Paty; Andrea Cercek; Garrett M Nash Journal: Ann Surg Oncol Date: 2020-08-25 Impact factor: 5.344