Background: Right-sided metastatic colorectal cancer (mCRC) patients have poor prognosis and achieve limited benefit fromfirst-line doublets plus a targeted agent. In this unplanned analysis of the TRIBE study, we investigated the prognostic andpredictive impact of primary tumor sidedness in mCRC patients and the differential impact of the intensification of thechemotherapy in subgroups defined according to both primary tumor sidedness andRASandBRAFmutational status. Patients and methods: Patients were randomized to receive upfront 5-fluoruracil, leucovorin, and irinotecan (FOLFIRI) plusbevacizumab or 5-fluoruracil, leucovorin, oxaliplatin, and irinotecan (FOLFOXIRI) plus bevacizumab. Tumors were defined asright- 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 andRASandBRAFstatus were included in thepresent analysis. Progression-free survival (PFS), overall survival (OS) and RECIST response rate were assessed according to tumorlocation andRASandBRAFmutational status. Results: Information about primary sidedness andRASandBRAFstatus was available for 358 (70.5%) out of 508 randomizedpatients. Patients with right-sided tumors (N¼173) presented shorter OS [23.7 versus 31.0 months, HR¼1.42 (95% CI 1.09–1.84),P¼0.010] and a trend toward shorter PFS [10.2 versus 11.5 months, HR¼1.24 (95% CI: 0.98–1.56),P¼0.083] than those withleft-sided tumors (N¼185), but these associations were no longer evident when adjusting forRASandBRAFstatus. Patients withright-sided tumors achieved more relative benefit from the intensification of the chemotherapy backbone in terms of both PFS(HR¼0.59 versus 0.89,Pfor interaction¼0.099) and OS (HR¼0.56 versus 0.99,Pfor interaction¼0.030) and this advantage wasindependent of theirRASandBRAFstatus. Conclusions: FOLFOXIRI plus bevacizumab may be regarded as a preferred first-line treatment option for clinically selectedpatients with right-sided metastatic colorectal cancer irrespective of theirRASandBRAFmutational status. Trial registration:clinicaltrials.gov identifier NCT00719797.
Primary tumor sidedness and benefit from FOLFOXIRI plus bevacizumab as initial therapy for metastatic colorectal cancer. Retrospective analysis of the TRIBE trial by GONO
Tonini G;
2018-01-01
Abstract
Background: Right-sided metastatic colorectal cancer (mCRC) patients have poor prognosis and achieve limited benefit fromfirst-line doublets plus a targeted agent. In this unplanned analysis of the TRIBE study, we investigated the prognostic andpredictive impact of primary tumor sidedness in mCRC patients and the differential impact of the intensification of thechemotherapy in subgroups defined according to both primary tumor sidedness andRASandBRAFmutational status. Patients and methods: Patients were randomized to receive upfront 5-fluoruracil, leucovorin, and irinotecan (FOLFIRI) plusbevacizumab or 5-fluoruracil, leucovorin, oxaliplatin, and irinotecan (FOLFOXIRI) plus bevacizumab. Tumors were defined asright- 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 andRASandBRAFstatus were included in thepresent analysis. Progression-free survival (PFS), overall survival (OS) and RECIST response rate were assessed according to tumorlocation andRASandBRAFmutational status. Results: Information about primary sidedness andRASandBRAFstatus was available for 358 (70.5%) out of 508 randomizedpatients. Patients with right-sided tumors (N¼173) presented shorter OS [23.7 versus 31.0 months, HR¼1.42 (95% CI 1.09–1.84),P¼0.010] and a trend toward shorter PFS [10.2 versus 11.5 months, HR¼1.24 (95% CI: 0.98–1.56),P¼0.083] than those withleft-sided tumors (N¼185), but these associations were no longer evident when adjusting forRASandBRAFstatus. Patients withright-sided tumors achieved more relative benefit from the intensification of the chemotherapy backbone in terms of both PFS(HR¼0.59 versus 0.89,Pfor interaction¼0.099) and OS (HR¼0.56 versus 0.99,Pfor interaction¼0.030) and this advantage wasindependent of theirRASandBRAFstatus. Conclusions: FOLFOXIRI plus bevacizumab may be regarded as a preferred first-line treatment option for clinically selectedpatients with right-sided metastatic colorectal cancer irrespective of theirRASandBRAFmutational status. Trial registration:clinicaltrials.gov identifier NCT00719797.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
