Adjuvant therapy with FOLFOX (leucovorin, 5-FU, oxaliplatin) significantly improved disease-free survival (DFS) compared with 5-FU and leucovorin (FL) in patients managed with preoperative chemotherapy and surgery for locally advanced rectal cancer, according to the long-term results of the ADORE trial (abstract 3501).
Although a difference in DFS occurred for the entire population of patients assigned to FOLFOX, a subgroup analysis identified groups with the most benefit, including those with yp stage III, yp N2, high-grade histology, minimally regressed tumor, and absence of lymphovascular or perineural invasion.
These data were presented by Tae Won Kim, MD, of the University of Ulsan College of Medicine, Seoul, Korea, at the 2018 American Society of Clinical Oncology (ASCO) Annual Meeting, held June 1–5 in Chicago.
According to Kim, use of adjuvant FOLFOX after preoperative chemoradiotherapy is based on extrapolated evidence from a trial of patients with colon cancer.
The current ADORE trial included 321 patients with resected rectal cancer and postoperative yp stage II/III after preoperative chemoradiotherapy with fluoropyrimidines alone. (The “yp” prefix refers to final staging after chemoradiotherapy [“y”] and pathologic examination postoperatively [“p”].)
Patients were randomly assigned to either adjuvant chemotherapy with FL or FOLFOX for 4 months. The primary endpoint was DFS.
At the median follow-up of 74.1 months, there were 46 DFS events in the FOLFOX arm and 65 in the FL arm. The 6-year DFS rate was 68.2% for FOLFOX, compared with 56.8% with FL (stratified hazard ratio [HR], 0.63; 95% CI, 0.43–0.93; P = .018).
The researchers also looked at outcome by stage. Among patients with yp stage III disease, the 6-year DFS was 63.2% for FOLFOX compared with 48.3% for FL, a difference of 14.9% (stratified HR, 0.59; 95% CI, 0.38–0.92; P = .019). For yp stage II disease, there was a nonsignificant difference of 8.3%; the 6-year DFS was 77.8% for FOLFOX and 69.5% for FL.
In terms of overall survival, there was no difference in outcomes between the two study arms. The 6-year OS rate was 78.1% for FOLFOX, compared with 76.4% for FL.
Commenting on these results, Cathy Eng, MD, of the University of Texas MD Anderson Cancer Center, wondered how they might impact her practice. “The ADORE trial is the best data to date that indicate that adjuvant FOLFOX in yp stage III patients results in improved disease-free survival in the traditional neoadjuvant chemoradiation paradigm of care,” Eng said.
She added that although the ADORE trial did not demonstrate improvement in OS, few studies of rectal cancer patients in this setting have done so.
Mehmet Sitki Copur, MD, of Saint Francis Cancer Center, Grand Island, Nebraska, also weighed in on the study findings, saying, "After chemoradiation, while 20% of the rectal cancer patients achieve complete pathologic response, 25% to 70% end up not being able to receive or complete adjuvant chemotherapy, due to various reasons. Adjuvant chemotherapy in rectal cancer patients has been extrapolated from two large metanalyses, as well as from colon cancer data. With the ADORE trial, now we do have prospective data which demonstrate overall improved disease-free survival with FOLFOX. Subgroup analyses provide further information for selective use of this regimen in this setting. It is also interesting and encouraging to see that in ADORE trial, 94% to 96% of patients completed planned cycles of adjuvant chemotherapy with a dose-intensity range of 86% to 95%.