Primary tumor sidedness has an impact on prognosis and treatment outcome in metastatic colorectal cancer: results from two randomized first-line panitumumab studies

Abstract

BackgroundPrevious studies have reported the prognostic impact of primary tumor sidedness in metastatic colorectal cancer (mCRC) and its influence on cetuximab efficacy. The present retrospective analysis of two panitumumab trials investigated a possible association between tumor sidedness and treatment efficacy in first-line mCRC patients with RAS wild-type (WT) primary tumors.Materials and methodsData from two randomized first-line panitumumab trials were analyzed for treatment outcomes by primary tumor sidedness for RAS WT patients. PRIME (phase 3; NCT00364013) compared panitumumab plus FOLFOX versus FOLFOX alone; PEAK (phase 2; NCT00819780) compared panitumumab plus FOLFOX versus bevacizumab plus FOLFOX. Primary tumors located in the cecum to transverse colon were coded as right-sided, while tumors located from the splenic flexure to rectum were considered left-sided.ResultsTumor sidedness ascertainment (RAS WT population) was 83% (n = 559/675); 78% of patients (n = 435) had left-sided and 22% (n = 124) had right-sided tumors. Patients with right-sided tumors did worse for all efficacy parameters compared with patients with left-sided disease in the RAS WT population and also in the RAS/BRAF WT subgroup. In patients with left-sided tumors, panitumumab provided better outcomes than the comparator treatment, including on median overall survival (PRIME: 30.3 versus 23.6 months, adjusted hazard ratio = 0.73, P = 0.0112; PEAK: 43.4 versus 32.0 months, adjusted hazard ratio = 0.77, P = 0.3125).ConclusionThe results of these retrospective analyses confirm that in RAS WT patients, right-sided primary tumors are associated with worse prognosis than left-sided tumors, regardless of first-line treatment received. RAS WT patients with left-sided tumors derive greater benefit from panitumumab-containing treatment than chemotherapy alone or combined with bevacizumab, including an overall survival advantage (treatment difference: PRIME 6.7 months; PEAK 11.4 months). No final conclusions regarding optimal treatment could be drawn for RAS WT patients with right-sided mCRC due to the relatively low number of paxtients. Further research in this field is warranted.Trial registration (Clinicaltrials.gov)PRIME (NCT00364013), PEAK (NCT00819780).

Antitumour immunity invoked by hepatic arterial infusion of first‐line oxaliplatin predicts durable colorectal cancer control after liver metastasis ablation: 8–12 years of follow‐up

“…42,43 Primary tumour right-sidedness and mutant RAS status have been reported as unfavourable prognostic factors. 20,21,23,46 We observed that wild-type RAS status was strongly associated with CLM conversion to resectability by oxaliplatin-HAI. 20,21,23,46 We observed that wild-type RAS status was strongly associated with CLM conversion to resectability by oxaliplatin-HAI.…”

Expression of programmed cell death protein 1 (PD-1) and its ligand PD-L1 in colorectal cancer: Relationship with sidedness and prognosis

“…23 , 24 Right-sided tumours, often defined as proximal to the splenic flexure, are generally poorly differentiated, diagnosed in more advanced tumour stages, displaying different molecular patterns, and carrying a poorer prognosis than left-sided tumours. 24 , 25 Several studies also demonstrate the importance of taking PTL into account when evaluating treatment response, 26-28 and retrospective analyses from large phase III trials have demonstrated that patients with right-sided tumours have less benefit from the addition of EGFR-targeted therapy. 29 …”

Selection criteria related to long-term survival following liver transplantation for colorectal liver metastasis

“…Overall survival (OS) after liver resections has been shown to be related to | 531 DUELAND Et AL. [5][6][7][8][9] Liver transplant (LT) is the standard of care for selected patients with malignant liver tumors such as hepatocellular carcinoma (HCC) and liver metastases from low-grade neuroendocrine tumors. About 20% of the patients with CRLMs are candidates for liver resections, 3 but about 60% to 70% have recurrence within 3 years.…”