For patients with high-risk stage II resected colorectal cancer (CRC), 3 months of adjuvant therapy with capecitabine plus oxaliplatin (CAPOX) may be significantly safer and nearly as effective as a 6-month course, based on results of the phase 3 TOSCA trial.
In contrast, a shortened duration of fluorouracil, leucovorin, and oxaliplatin (FOLFOX) may negatively impact 5-year recurrence-free survival, reported Fausto Petrelli, MD, of ASST Bergamo Ovest in Treviglio, Italy, and colleagues.
An earlier analysis from the Italian Three or Six Colon Adjuvant (TOSCA) trial showed that 6 months of oxaliplatin-based adjuvant chemotherapy was superior to a 3-month regimen among patients with stage III CRC, the investigators wrote in.
To determine if this finding carried over to patients with less advanced disease, the investigators recruited 1,254 patients with high-risk stage II resected CRC who were treated at 130 centers in Italy. Patients were randomized in a 1:1 ratio to receive a 6-month or 3-month regimen of oxaliplatin-based chemotherapy (either FOLFOX or CAPOX). The primary outcome was a test for noninferiority between the two durations, with the null hypothesis rejected by a hazard ratio of at least 1.2.
Almost two-thirds (61.9%) of patients received FOLFOX, while the remainder (38.1%) received CAPOX. Across all of these patients, 6 months of therapy was associated with a 5-year recurrence-free survival rate of 88.2%, compared with 82.2% for the 3-month course. This translates to a hazard ratio of 1.41, which is insufficient to reject noninferiority (P = .86) and suggests a longer duration of oxaliplatin-based chemotherapy is significantly more effective.
However, when the CAPOX and FOLFOX subgroups were considered independently, distinct efficacy trends emerged. The difference in the 5-year recurrence-free survival rate between 6 months and 3 months of CAPOX was only slightly in favor of the longer course (0.76%). There was a much greater survival rate difference of 8.56% that favored the 6-month course of FOLFOX.
The investigators noted that 6 months of adjuvant therapy was associated with significantly more adverse events than a 3-month course, particularly for grade 3/4 neuropathy (8.4% vs. 1.3%; P less than .001). Taken together, the findings suggest the shortened CAPOX regimen may be a viable option.
“[E]ither 3 months of CAPOX or 6 months of FOLFOX treatment can be used whenever an oxaliplatin doublet is indicated for use in patients with stage II CRC,” the investigators wrote. At the same time, they suggested the subgroup findings be interpreted with caution, as the study was not powered for these analyses.
“[T]he 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,” the investigators concluded.
The study was funded by the Italian Group for the Study of Digestive Tract Cancers (GISCAD) Foundation and Agenzia Italiana del Farmaco. The investigators disclosed relationships with Servier, Merck, Bristol-Myers Squibb, and other companies.
SOURCE: Petrelli F et al. JAMA Oncol. 2020 Feb 13. doi:.