Impact of Age on Efficacy of Newer Adjuvant Therapies in Patients with Stage II/III Colon Cancer
Available data suggest that patients with stage II/III colon cancer receive similar benefit from intravenous fluorouracil (5-FU) adjuvant therapy regardless of age. Combination regimens and oral fluoropyrimidine therapy are now standard treatments in this setting. Nadine J. McCleary, MD, MPH, and colleagues from the ACCENT Collaborative Group analyzed the impact of age on colon cancer recurrence and survival after adjuvant therapy with the newer options using the ACCENT database. Their findings suggest a reduced benefit of adding oxaliplatin to fluoropyrimidines in patients aged ≥ 70 years and no age-related difference in the comparative efficacy of oral fluoropyrimidines vs intravenous 5-FU. The results were published online in the Journal of Clinical Oncology.
The analysis included 11,953 patients aged < 70 years and 2,575 aged ≥ 70 years from seven adjuvant therapy trials evaluating the addition of oxaliplatin or irinotecan to fluoropyrimidines or comparing oral fluoropyrimidines (capecitabine [Xeloda], tegafur-uracil) with intravenous 5-FU in patients with stage II/III colon cancer. The age groups were similar with respect to sex and assignment to experimental or control treatment. Stage II disease was slightly more common among younger patients (23% vs 19%). The endpoints analyzed were disease-free survival, overall survival, and time to recurrence.
Among all patients, the hazard ratios (HRs) for experimental vs control treatments were significant for disease-free survival (0.85), overall survival (0.87), and time to recurrence (0.84) for patients aged < 70 years and nonsignificant (1.05, 1.08, and 1.06, respectively) for those aged ≥ 70 years. There was a significant interaction by age for disease-free survival (P = .001), overall survival (P = .004), and time to recurrence (P = .002), indicating that the benefits of the experimental treatments were limited to younger patients overall.
Oxaliplatin-based Trials
In three trials assessing the addition of oxaliplatin to fluoropyrimidines (intravenous 5-FU/leucovorin in two and oral capecitabine in one), hazard ratios for the oxaliplatin vs control arms among 5,420 patients aged < 70 years were 0.78 for disease-free survival, 0.83 for overall survival, and 0.77 for time to recurrence, with all being statistically significant. Hazard ratios among 1,119 patients aged ≥ 70 years were 0.94, 1.04, and 0.86, respectively, with none being significant.
The P values for interaction by age were .09 for disease-free survival, .36 for time to recurrence, and .05 for overall survival, indicating lack of a significant interaction by age for disease-free survival and time to recurrence and a borderline significant interaction for overall survival.
The authors noted that these findings could suggest that oxaliplatin provides a reduction in recurrence risk in a subset of older patients, with overall survival benefit diminishing with increased mortality from other causes in older patients over time; similarly, the lack of a significant interaction by age for disease-free survival suggests a disease-free survival benefit in a subset of older patients.
Irinotecan-based Trials
In two trials assessing the addition of irinotecan to intravenous 5-FU/leucovorin, hazard ratios for the irinotecan vs control arms among 3,750 patients aged < 70 years were 0.89 for disease-free survival, 0.90 for overall survival, and 0.88 for time to recurrence, with those for disease-free survival and time to recurrence being significant. By comparison, hazard ratios among 699 patients aged ≥ 70 years were 1.19, 1.11, and 1.35, respectively, with none being statistically significant. There was a significant interaction by age for disease-free survival (P = .02) and time to recurrence (P = .002), but no significant interaction for overall survival (P = .13).
Oral Fluoropyrimidine Trials
In two noninferiority trials comparing the addition of oral fluoropyrimidines to intravenous 5-FU/leucovorin, none of the hazard ratios for the oral fluoropyrimidine vs control arms were significant among 2,783 patients aged < 70 years or 757 aged ≥ 70 years for disease-free survival (0.91 and 1.14), overall survival (0.90 and 1.13), and time to recurrence (0.90 and 1.20). There were no significant interactions by age for disease-free survival (P = .13), overall survival (P = .16), or time to recurrence (P = .09), suggesting that the benefit of oral fluoropyrimidines is similar to that of intravenous 5-FU regardless of age.
As stated by the authors, “Our findings suggest that the benefit of oxaliplatin compared with intravenous 5-FU/leucovorin is restricted to patients aged < 70 years for overall survival. For patients age ≥ 70 years, oxaliplatin may provide a disease-free survival benefit for a subset of older adults; however, we cannot establish which subsets of older adults experience benefit. For this reason, the data also support fluoropyrimidine monotherapy as an appropriate treatment option. Fluoropyrimidine monotherapy with either 5-FU/leucovorin or capecitabine is an appropriate adjuvant treatment option for patients age ≥ 70 years. Further study is needed to identify which subsets of older patients derive potential benefit from oxaliplatin-based chemotherapy.”
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
