in the XELOX arm (20%) than in the FOLFOX-4 arm (13%) withdrew because of adverse events.
“These findings demonstrate that XELOX is an effective and well-tolerated alternative to FOLFOX-4 as second- line therapy in metastatic colorectal cancer,” Dr. Mace Rothenberg, MD, Vanderbilt Ingram Cancer Center, Nashville, concluded.
The findings of the NO16967 trial support those from a similar study in the first-line setting reported at the ASCO annual meeting [Cassidy J et al. ASCO 2007. Abstract 4030].
Updated Efficacy Results of the MOSAIC Trial, Including Survival, with a Median Follow-Up of Six Years
Approximately 1 million new cases of colon cancer arise each year worldwide. It has been demonstrated that patients who receive leucovorin (LV)/5-fluorouracil (5-FU) after surgical resection of the tumor have better prognoses than those who undergo surgery alone. Recent data suggest that oxaliplatin, in combination with LV5FU, provides an even greater survival advantage. The MOSAIC trial was designed to compare the efficacy of LV5FU with LV5FU plus oxaliplatin (FOLFOX).
The primary endpoint of this study was 3-year disease- free survival (DFS); these results were presented in 2003 and were published thereafter [André et al. N Engl J Med 2004]. DFS was chosen as the primary endpoint based on data published by Sargent et al. [Sargent et al. J Clin Oncol 2005] that showed that clinical trials looking at DFS can proceed more rapidly, allowing more timely conclusions of treatment superiorities. Additionally, this study showed that 3-year DFS correlates well with 5-year overall survival (OS). The secondary endpoints were safety and OS.
The 5-year DFS in the MOSAIC study confirms the results observed after 3 years (Table 1) that FOLFOX is superior to LV5FU in this setting. At 5 years, there was a 5.9% difference in favor of FOLFOX treatment over LV5FU. When stratified by disease stage, there was a 7.5% survival benefit with FOLFOX in stage III disease (p=0.005), while there was a non-statistically significant difference in survival benefit of only 3.8% with FOLFOX in stage II patients. However, high-risk stage II patients did appear to benefit more from FOLFOX therapy than with LV5FU (Table 2).
Table 1. DFS in the MOSAIC Trial at 3 and 5 Years. 3 Years
April 2003 FOLFOX4 LV5FU2 FOLFOX4 Median follow-up, months Events (%) DFS (%) HR [95% CI] p value 37.9 21.1 78.2 0.77 [0.65-0.91] 0.002 37.8 26.1 72.9 73.5 27.1 73.3 0.80 [0.68-0.93] 0.003
5 Years June 2006 LVFU52 73.4 32.1 67.4
Table 2: 5-Year DFS Shown By Disease Stage. 5 Year DFS %
HR FOLFOX4 ITT (overall population) Stage III Stage II High-risk stage II (n=576) Low-risk stage II (n=323) 73.3 66.4 83.7 82.1 86.3 LV5FU2 67.4 58.9 79.9 74.9 88.1 [95% CI] 0.80 [0.68-0.93] 0.78 [0.65-0.93] 0.84 [0.62-1.14] 0.74 [0.52-1.06] 1.22 [0.66-2.26] 0.258 0.005 p value 0.003
The toxicity data, published previously [André et al. N Engl J Med 2004], showed two limiting toxicities with FOLFOX therapy: grade 3 and 4 neutropenia, and grade 3 neuropathy. Long-term safety data showed that there were no differences in the development of secondary cancers between the two arms. Also, there appeared to be a recovery in the degree of peripheral sensory neuropathy; the number of patients with grade 3 neuropathy decreased by about 15% from the time of treatment out to 4 years.
Highlights from the American Society of Clinical Oncology Annual Meeting 2007
21
Page 1 |
Page 2 |
Page 3 |
Page 4 |
Page 5 |
Page 6 |
Page 7 |
Page 8 |
Page 9 |
Page 10 |
Page 11 |
Page 12 |
Page 13 |
Page 14 |
Page 15 |
Page 16 |
Page 17 |
Page 18 |
Page 19 |
Page 20 |
Page 21 |
Page 22 |
Page 23 |
Page 24 |
Page 25 |
Page 26 |
Page 27 |
Page 28 |
Page 29 |
Page 30