Among patients with stage III colon cancer, comparison of patients aged >70 with those <70 years showed that elderly patients tolerated adjuvant oxaliplatin/flouropyrimidines therapy less well and had poorer relapse-free interval (RFI) rates, according to findings from a large subgroup analysis of the phase III TOSCA presented at the ESMO Virtual Congress 2020 by Sara Lonardi of the IRCCS Istituto Oncologico Veneto in Padova, Italy (lead author Gerardo Rosati of the Azienda Ospedaliera Regionale S. Carlo di Potenza, Potenza, Italy).
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 non-convergent results and reduced benefit for patients over 70 years.
Prompted by these reports, Dr. Rosati and colleagues evaluated the activity of this treatment according to RFI in patients <70 years compared with those >70 years; RFI was defined as time from randomisation to relapse or last disease assessment.
The investigators used data from the 3,759 patients with colon cancer participating in the multicentre, phase III, TOSCA study (NCT0064660). In TOSCA, the patients were randomised to receive either 3 or 6 months of FOLFOX (FULV plus oxaliplatin) or CAPOX (capecitabine plus oxaliplatin).
This analysis comprised 2,360 patients with Stage III disease; of these 1,667 patients were aged under 70 (younger cohort) and 693 were aged 70 or more years (elderly cohort).
Comparison of the cohorts regarding patient characteristics showed 10.5% of elderly versus 3.3% younger patients had ECOG performance status (PS) 1 (p < 0.001), 40.8% versus 45.1% female patients (p = 0.057), and 90.9% versus 84.3% more T3/T4 tumours (p < 0.001), respectively. Elderly patients also had a greater number of poorly differentiated (G3) tumours than younger patients (28.3% versus 24.2%, p = 0.039) and tumours that were located on the right side of the colon (40.9% versus 26.6%; p < 0.001) respectively.
Elderly patients required more dose reductions and interruption
In the younger cohort, the median follow-up was 62.5 months and 60.6 months in the over 70 patients.
During follow-up, patients in the elderly versus younger cohorts experienced 46.7% versus 41.4% dose reductions (p = 0.018), and 26.1% versus 19.3% treatment interruptions, respectively (p < 0.001).
Although more disease recurrence was seen in the elderly patients, multivariate analysis did not find a significant association between age and RFI
Disease recurrence occurred more frequently in patients >70 years; recurrence rates were 24.2% in elderly compared to 20.3% in younger patients (p = 0.033).
Upon multivariable analysis of the RFI, which corrected for sex, ECOG PS, tumour site, stage, grade, treatment, treatment duration and dose reduction, no statistically significant effect of age on RFI following treatment was found (hazard ratio [HR] 1.19).
A significant impact on RFI was observed only with stage III high versus low risk colon cancer (HR 2.05; 95% confidence interval, 1.71-2.46, p < 0.001)
Primary endpoint, relapse-free interval: Univariate cox model showed a statistically significant difference in relapse-free interval, with an increase in the risk of relapse of 27% in the elderly population.
© Gerardo Rosati.
Conclusions
Among patients with stage III colon cancer treated with an oxaliplatin-based adjuvant therapy, elderly patients aged 70 and more years demonstrated different tolerability of treatment and a potential reduction of benefit compared with patients aged 70 years and younger. 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.
No external funding was reported fort this study.
Reference
399O – Rosati G, Galli F, Lonardi S, et al. Oxaliplatin plus fluoropyrimidines as adjuvant therapy for colon cancer in elderly patients: A subgroup analysis from TOSCA trial. ESMO Virtual Congress 2020.