NSABP C-07: No evidence adjuvant oxaliplatin improved OS in colon cancer

Yothers G. J Clin Oncol. 2011;doi:10.1200/JCO.2011.36.4539.

Issue: September 25, 2011

Although DFS results remained strong, the addition of oxaliplatin to fluorouracil and leucovorin did not improve OS for patients with stage II or III colon cancer, according to updated 5-year results from the NASBP C-07 trial.

However, researchers said an unplanned subset analysis suggested that there may be a beneficial OS effect associated with oxaliplatin for patients aged younger than 70 years.

Researchers recruited 2,409 eligible patients with colon cancer who had undergone potentially curative surgical resection with no evidence of residual malignant disease. Those patients were then randomly assigned to fluorouracil plus leucovorin (FULV, n=1,209) and 1,200 were assigned to fluorouracil/leucovorin plus oxaliplatin (FLOX).

Initial results were released after 3.5 years of follow-up and showed that FLOX significantly improved DFS. In these results, there were 503 DFS events in the FULV group and 432 events for patients assigned to FLOX (HR=0.82; 95% CI, 0.72-0.93). FLOX was associated with an 18% relative reduction in risk for a DFS event. Overall 5-year DFS was 69.4% for FLOX vs. 64.2% for FULV.

There were 362 deaths in the FULV group and 320 in the FLOX group, a difference that researchers said was not significant (HR=0.88; 95% CI, 0.75-1.02). FLOX was associated with a 12% relative reduction in the risk for death. Estimated 5-year OS was 78.4% for FULV and 80.2% for FLOX.

When researchers analyzed patients by age, they found that OS was superior for patients aged younger than 70 years assigned to FLOX (HR=0.80; 95% CI, 0.68-0.95). The regimen was also associated with a 3.1% improvement in estimated 5-year OS for younger patients (81.8% vs. 78.8%). Researchers said treatment regimen did not have a significant effect on OS in older patients, but nominal OS at 5 years was 4.7% worse for patients treated with FLOX compared with patients treated with FULV (71.6% vs. 76.3%).

Overall, there was an 18% decrease in the hazard of death or recurrence by adding oxaliplatin to bolus 5-FU chemotherapy. Oxaliplatin remains a viable option, particularly for stage III colon cancer, and the results of this study confirm what we've seen in both the MOSIAC and the XELOXA trials. We now have three oxaliplatin trials that have been done the in adjuvant setting and all three show a clear improvement in DFS. The MOSIAC data, which have longer follow-up than the NSABPC-07 trial, also show an overall survival advantage. This paper in no way diminishes the importance of oxaliplatin as a component of our chemotherapy for, at the very least, stage III colon cancer, though oxaliplatin may be less important for certain stage II colon cancers.

I would exercise caution in interpreting the results in patients over 70. One, it's a subset analysis so by definition the trial was not powered to look at that group. Two, the over 70 group is so heterogeneous that it's difficult to know what to do with an age cutoff. This just calls to attention that we need to discover a better way of looking at our elderly population and determining who can benefit from aggressive therapy and who cannot. These results caution us as oncologists to really get a better feel for our patients.

- Blase N. Polite, MD, MPP
Assistant Professor of Medicine with the Center for Gastrointestinal Oncology,
University of Chicago

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