Oligometastatic colorectal cancer: prognosis, role of locoregional treatments and impact of first-line chemotherapy-a pooled analysis of TRIBE and TRIBE2 studies by Gruppo Oncologico del Nord Ovest.

ABSTRACT

BACKGROUND: Oligometastatic disease (OMD) identifies tumours with limited metastatic spread. OMD definition is not univocal and no data from clinical trials are available about the prognostic effect of OMD in metastatic colorectal cancer (mCRC), the impact of locoregional treatments (LRTs) and the effect of chemotherapy intensification in these patients. The role of tumour burden (TB) in driving therapeutic choices is also debated. PATIENTS AND METHODS: We performed a pooled analysis of phase III TRIBE and TRIBE2 studies comparing FOLFOXIRI/bevacizumab (bev) to doublets (FOLFOX or FOLFIRI)/bev. Patients were grouped in OMD versus non-OMD based on the European Society for Medical Oncology definition. Among patients with OMD, those with OMD/low TB were compared with all the others. RESULTS: Of 1187 patients enrolled, 1096 were classified as OMD (N = 312 [28%]) or non-OMD (N = 784 [72%]). Among patients with OMD, 126 (40%) were OMD/low TB. OMD was associated with longer progression-free survival (14.0 versus 10.1 months; p < 0.01) and overall survival (38.2 versus 22.0 months; p < 0.01). These results were confirmed in multivariable models. The benefit provided by FOLFOXIRI/bev compared with doublets/bev did not differ in accordance with OMD and TB (p for interaction >0.05). Patients with OMD underwent LRTs more frequently (p < 0.01) and those with OMD/low TB had higher chance to undergo LRTs after the first progression (p < 0.01). CONCLUSIONS: OMD is a positive prognostic factor in mCRC. The benefit from the upfront treatment intensification is independent of the metastatic spread extent and TB. LRTs should be highly considered in these patients, mainly during the first-line therapy but also at later stages of treatment history in selected cases.