Optimal Duration Of Oxaliplatin-Based Chemotherapy In High-Risk Stage II CRC Remains Unclear

Author: By Laura Cowen, medwireNews Reporter

medwireNews: A 3-month regimen of FOLFOX (fluorouracil, leucovorin, and oxaliplatin) or CAPOX (capecitabine plus oxaliplatin) cannot be considered non-inferior to a conventional 6-month regimen for relapse-free survival (RFS) in patients with high-risk stage II resected colorectal cancer (CRC), a subgroup analysis of the TOSCA study data show. 

The phase III trial included 1254 patients (mean age 62.4 years, 45.1% women) with high-risk stage II resected CRC who were randomly assigned to receive 3 months (n=621) or 6 months (n=633) of treatment with their physician’s choice of either FOLFOX (61.9%) or CAPOX (38.1%) each at the standard dose. 

After a median 62 months of follow-up, the 5-year RFS was 82.2% among the patients who received 3 months of treatment and 88.2% among those who received 6 months of treatment. This gave a significant hazard ratio of 1.41 in favour of the 6-month arm and a 95% confidence interval that crossed the predefined noninferiority limit of 1.20. 

Furthermore, the researchers note that the difference in favour of 6 months’ treatment duration was “much larger than that reported in the same TOSCA study for patients with stage III [CRC]” suggesting that “that stage II needs a longer adjuvant treatment than stage III.” 

When the team analysed the data by treatment regimen, they found that, for CAPOX, 5-year RFS was similar with 3 and 6 months of treatment, at 84.6% and 85.4%, respectively. 

By contrast, 5-year RFS was significantly shorter among the patients who received 3 months of FOLFOX relative to those who received 6 months of this regimen, at 81.1% versus 89.6%. 

Writing in JAMA Oncology, Fausto Petrelli, from American SamoaST Bergamo Ovest in Treviglio, Italy, and co-authors say this “possible regimen effect” suggests “that either 3 months of CAPOX or 6 months of FOLFOX therapy can be used whenever an oxaliplatin doublet is indicated for treatment of patients with stage II [CRC].” 

However, they also point out that a test for an interaction between duration and regimen was not statistically significant. 

In terms of safety, the investigators report that fewer patients in the 3-month arm reported severe toxic effects relative to those in the 6-month arm, with statistically significant differences observed for neutropenia (20.7 vs 27.6%), diarrhoea (5.0 vs 6.4%), and allergic reactions (0.5 vs 2.0%), as well as grade 3 or 4 neuropathy (1.3 vs 8.4%). 

Fausto Petrelli and colleagues therefore conclude that “the utility of oxaliplatin in stage II [CRC] remains unclear, and the choice between 6 months of fluoropyrimidine-based chemotherapy and 3 or 6 months of oxaliplatin-based chemotherapy must be made on an individual basis.” 

Reference 

Petrelli F, Labianca R, Zaniboni A, et al. Assessment of duration and effects of 3 vs 6 months of adjuvant chemotherapy in high-risk stage II colorectal cancer. A subgroup analysis of the TOSCA randomized clinical trial. JAMA Oncol 2020; Advance online publication 13 February 2020. doi: 10.1001/jamaoncol.2019.6486