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Elderly Patients With Advanced Colorectal Cancer Treated With Adjuvant Oxaliplatin Plus Fluoropyrimidines: Tolerability and Benefit


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Among patients with stage III colon cancer, patients aged 70 or older were less tolerant of adjuvant oxaliplatin/flouropyrimidine therapy, in addition to having poorer relapse-free interval rates on the regimen, according to findings from a large subgroup analysis of the phase III TOSCA trial presented by Lonardi et al at the ESMO Virtual Congress 2020 (Abstract 399O).

The authors noted that previous studies suggested that the standard of care combination of oxaliplatin and fluoropyrimidines for the adjuvant therapy of stage III colon cancer demonstrated nonconvergent results and reduced benefit for patients older than 70.

TOSCA

Prompted by these reports, the authors evaluated the activity of this treatment according to relapse-free interval in patients younger than 70 compared with those aged 70 or older. Relapse-free interval was defined as time from random assignment to relapse or last disease assessment.

The investigators used data from the 3,759 patients with colon cancer participating in the multicenter phase III TOSCA study. In TOSCA, patients were randomly assigned to receive either 3 or 6 months of FOLFOX (leucovorin, fluorouracil, and oxaliplatin) or CAPOX (capecitabine plus oxaliplatin).

This analysis was comprised of 2,360 patients with stage III disease; of these, 1,667 patients were younger than 70 and 693 were age 70 or older.

Comparison of the cohorts regarding patient characteristics showed 10.5% of elderly versus 3.3% younger patients had an Eastern Cooperative Oncology Group (ECOG) performance status of 1 (P < .001); 40.8% vs 45.1% of patients were female (P = .057); and 90.9% vs 84.3% had T3/T4 tumors (P < .001). Elderly patients also had a greater number of poorly differentiated tumor’s than younger patients (28.3% vs 24.2%, P = .039) and more tumors that were located on the right side of the colon (40.9% vs 26.6%; P < .001).

KEY POINTS

  • During follow-up, 46.7% of patients in the elderly vs 41.4% in the younger cohort experienced dose reductions, and 26.1% vs 19.3% experienced treatment interruptions.
  • Recurrence rates were 24.2% in elderly patients compared to 20.3% in younger patients.
  • Upon multivariable analysis of the relapse-free interval, no statistically significant effect of age on relapse-free interval following treatment was found. A significant impact on relapse-free interval was observed only with stage III high-risk vs low-risk colon cancer.

Dose Reductions, Treatment Interruptions, and Relapse-Free Interval

In the younger cohort, the median follow-up was 62.5 months; in the older cohort, it was 60.6 months.

During follow-up, 46.7% of patients in the elderly vs 41.4% in the younger cohort experienced dose reductions (P = .018), and 26.1% vs 19.3% experienced treatment interruptions (P < .001).

Disease recurrence occurred more frequently in the older cohort; recurrence rates were 24.2% in elderly patients compared to 20.3% in younger patients (P = .033).

Upon multivariable analysis of the relapse-free interval—which corrected for sex, ECOG performance status, tumor site, stage, grade, treatment, treatment duration, and dose reduction—no statistically significant effect of age on relapse-free interval following treatment was found (hazard ratio [HR] = 1.19). A significant impact on relapse-free interval was observed only with stage III high-risk vs low-risk colon cancer (HR = 2.05, 95% confidence interval = 1.71–2.46, P < .001).

Among patients with stage III colon cancer treated with an oxaliplatin-based adjuvant therapy, elderly patients aged 70 or older demonstrated different tolerability of treatment and a potential reduction of benefit compared to younger patients. Additional consideration is warranted in elderly patients regarding their general health status, comorbidities, and the management of the expected side effects, according to the authors.

Disclosure: For full disclosures of the study authors, visit oncologypro.esmo.org.

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®.
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