ADOREable.

Top Line: Let’s try this again because we’re still confused. Why do we give adjuvant chemo for rectal cancer?

The Study: Neoadjuvant chemoradiation (nCRT) became the standard approach for stage II/III rectal cancer largely based on the German Rectal Study Group trial. Compared with adjuvant chemoradiation, local recurrence, acute toxicity, and late toxicity were all better. At the same time, the R-01 trial showed that adjuvant chemo alone but not adjuvant radiation alone improved survival. Then the follow up R-02 trial demonstrated an incremental improvement in local control when radiation was added to adjuvant chemo. In the collective conscious, this seems to have established the standard that 1) radiation needs concurrent chemo and vice versa, 2) chemoradiation is best done pre-op, and 3) additional chemo is beneficial. To throw a wrench in things, a 2015 meta-analysis found that adjuvant 5FU-based chemo does not appear to incrementally improve survival or distant recurrence rates when given after nCRT. Here we have long-term results of the ADORE trial that randomized patients to 5-FU/leucovorin versus FOLFOX after nCRT followed by total mesorectal excision. Importantly, eligibility was determined based on pathologic stage, which had to be ypT3/4 or ypN+. The initial results demonstrated a significant improvement in the primary endpoint of 3-year disease-free survival (DFS) from 63 → 72%. And here, at 6 years, that benefit was maintained with FOLFOX increasing DFS from 57 → 68%.

TBL: In rectal cancer patients with a poor response to neoadjuvant chemoradiation, the addition of oxaliplatin to adjuvant 5FU provides an incremental improvement in disease-free survival. | Hong, J Clin Oncol 2019