Abstract
In the pivotal Bevacizumab-Avastin Adjuvant (AVANT) trial, patients with high-risk stage II colon cancer (CC) had 5-year and 10-year overall survival (OS) rates of 88% and 75%, respectively, with adjuvant fluorouracil and oxaliplatin-based chemotherapy; however, the trial did not demonstrate a disease-free survival (DFS) benefit of adding bevacizumab to oxaliplatin-based chemotherapy in stage III CC and suggested a detrimental effect on OS. The Long-term Survival AVANT (S-AVANT) study was designed to collect extended follow-up for patients in the AVANT trial. To explore the efficacy of adjuvant bevacizumab combined with oxaliplatin-based chemotherapy in patients with high-risk, stage II CC. This prespecified secondary end point analysis of the AVANT and S-AVANT studies included 573 patients with curatively resected high-risk stage II CC and at least 1 of the following criteria: stage T4, bowel obstruction or perforation, blood and/or lymphatic vascular invasion and/or perineural invasion, age younger than 50 years, or fewer than 12 nodes analyzed. The AVANT study was a multicenter randomized stage 3 clinical trial. Data were collected from December 2004 to February 2019, and data for this study were analyzed from March to September 2019. Patients were randomly assigned to receive 5-fluorouracil, leucovorin, and oxaliplatin (FOLFOX4), FOLFOX4 with bevacizumab, or capecitabine and oxaliplatin (XELOX) with bevacizumab. The primary end points of this secondary analysis were DFS and OS in patients with high-risk stage II CC. The AVANT study included 3451 patients, of whom 573 (16.6%) had high-risk stage II CC (192 [33.5%] randomized to FOLFOX4 group; 194 [33.9%] randomized to FOLFOX4 with bevacizumab group; 187 [32.6%] randomized to XELOX with bevacizumab group). With a median (interquartile range) age of 57.0 (47.2-65.7) years, the study population comprised 325 men (56.7%) and 248 women (43.3%). After a median (interquartile range) follow-up of 6.9 (6.1-11.3) years, the 3-year DFS and 5-year OS rates were 88.2% (95% CI, 83.7%-93.0%) and 89.7% (95% CI, 85.4%-94.2%) in the FOLFOX4 group, 86.6% (95% CI, 81.8%-91.6%) and 89.7% (95% CI, 85.4%-94.2%) in the FOLFOX4 with bevacizumab group, and 86.7% (95% CI, 81.8%-91.8%) and 93.2% (95% CI, 89.6%-97.0%) in the XELOX with bevacizumab group, respectively. The DFS hazard ratio was 0.94 (95% CI, 0.59-1.48; P = .78) for FOLFOX4 with bevacizumab vs FOLFOX4 and 1.07 (95% CI, 0.69-1.67; P = .76) for XELOX with bevacizumab vs FOLFOX4. The OS hazard ratio was 0.92 (95% CI, 0.55-1.55; P = .76) for FOLFOX4 with bevacizumab vs FOLFOX4 and 0.85 (95% CI, 0.50-1.44; P = .55) for XELOX with bevacizumab vs FOLFOX4. In this secondary analysis of data from the AVANT trial, adding bevacizumab to oxaliplatin-based chemotherapy was not associated with longer DFS or OS in patients with high-risk stage II CC. The findings suggest that the definition of high-risk stage II CC needs to be revisited. ClinicalTrial.gov Identifiers: AVANT (NCT00112918); S-AVANT (NCT02228668).
Highlights
Colorectal cancer (CRC) is the fourth most common cancer in the world and the fifth leading cause of death.[1]
Meaning The findings of this study suggest that adding bevacizumab to oxaliplatin-based chemotherapy was not associated with longer disease-free survival (DFS) or overall survival (OS) in patients with high-risk stage II colon cancer and that the definition of highrisk stage II colon cancer needs to be revisited
In this secondary analysis of data from the AVANT trial, adding bevacizumab to oxaliplatin-based chemotherapy was not associated with longer DFS or OS in patients with high-risk stage II CC
Summary
Colorectal cancer (CRC) is the fourth most common cancer in the world and the fifth leading cause of death.[1]. The survival benefit of 6-month adjuvant therapy with bolus 5-fluorouracil/leucovorin (5-FU/LV) in patients with resected, node-positive CC (stage III) was established in the 1990s.5-7. It was later superseded in trials by infusional 5-FU/LV regimens, which showed an improved safety profile.[8] The efficacy of 5-FU/LV in adjuvant therapy for stage II CC was established by the Quick and Simple and Reliable (QUASAR) study.[9] In the population with stage II disease, this study showed that adjuvant chemotherapy decreased the relative risk of recurrence by 29% (hazard ratio [HR], 0.71; 95% CI, 0.54-0.92), but there was no difference in OS (HR, 0.83; 95% CI, 0.65-1.07). Considering these results, adjuvant treatment for stage II CC is discussed according to tumor-related prognostic factors and should be balanced with patient’s comorbidity and life expectancy
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