Oxaliplatin-based chemo for stage II CRC: Shorter regimen better?
A pooled analysis of six trials failed to show noninferiority of a 3-month regimen to a 6-month regimen of oxaliplatin-based chemotherapy for patients with high-risk, stage II colorectal cancer (CRC).
The 5-year disease-free survival (DFS) rates were 80.7 percent in the 3-month arm and 83.9 percent in the 6-month arm, yielding an absolute difference of 3.2 percent and a hazard ratio (HR) of 1.17 (80 percent confidence interval [CI], 1.05–1.31). “[Based on] the forest plot, the upper limit of the CI crosses the noninferiority margin of 1.2. Hence, we cannot conclude that 3 months of treatment is noninferior to 6 months,” said Dr Dawn Chong from the National Cancer Centre Singapore who presented the findings at BASCO 2019.
“However, the 3-month treatment regimen led to less toxicities,” said Chong, citing the significantly lower overall adverse event (AE) rates in the 3-month vs the 6-month arm (60 percent vs 82 percent; p<0.0001), particularly the incidences of neurotoxicity (13 percent vs 36 percent; p<0.0001) and diarrhoea (12 percent vs 19 percent; p=0.0002).
Investigators from the IDEA* collaboration prospectively pooled results from six randomized phase III trials evaluating the duration of adjuvant oxaliplatin-based chemotherapy in CRC, of which four** included individuals with high-risk stage II disease (n=3,332, median age 64.2 years, 56.5 percent male). Participants had been randomized 1:1 to receive either 3 or 6 months of a CAPOX*** or FOLFOX# regimen. Median follow-up ranged from >2 years to >5 years. [BASCO 2019, abstract 3501]
CAPOX over FOLFOX?
When stratified according to regimen, the 5-year DFS rates among patients in the FOLFOX arm who received the 3-month regimen were lower than that of those who received the 6-month regimen (79.2 percent vs 86.5 percent), generating an absolute difference of 7.3 percent. “[This] strongly suggests inferiority of the 3-month FOLFOX regimen to the 6-month regimen,” said Chong. However, the 3-month regimen was less toxic than the 6-month regimen as evidenced by the lower AE rates (64 percent vs 87 percent; p<0.0001).
The 5-year DFS rates were similar in CAPOX recipients who received the regimen for 3 and 6 months (81.7 percent and 82 percent, respectively), suggesting that the shorter CAPOX regimen is as good as the longer one. As in FOLFOX, the 3-month regimen was also less toxic than the 6-month regimen (57 percent vs 79 percent; p<0.0001).
“[As some of] our data suggested the noninferiority of 3-month CAPOX to a 6-month regimen … we can offer this option to selected stage II CRC patients with high-risk features,” said Chong. “[However, as] IDEA did not compare FOLFOX and CAPOX … we cannot compare these regimens,” she added.