Elderly patients with stage-III colorectal cancer may have reduced benefit and lower treatment tolerability to adjuvant therapy with oxaliplatin plus fluoropyrimidines, a new study presented at ESMO 2020 has concluded.
According to the multi-center team of Italian investigators behind the trial, previous research of adjuvant therapy with combination oxaliplatin and fluoropyrimidines in stage-III colon cancer has yielded “non-convergent results and a reduced benefit for those over the age of 70 years.”
With that in mind, they set out to shed some more light on this relationship by assessing the impact of age (categorized as <70 or ≥70 years) on relapse-free interval in this patient population. Relapse-free survival was defined as the time from randomization to relapse or last disease evaluation.
In total, 3,759 patients were enrolled from 130 sites as part of the phase-III TOSCA study (NCT0064660). Of these, 2,360 had stage-III disease, 1,667 of whom were younger than 70 and 693 who were at least 70 years of age.
The participants were randomized to receive either FOLFOX therapy (5-fluouracil, leucovorin, and oxaliplatin) or CAPOX therapy (capecitabine plus oxaliplatin) for three or six months.
With respect to patient demographics, patients at least 70 years of age had an ECOG performance status that was more often equal to 1 (10.5% vs 3.3%; p <0.001), fewer women (40.8% vs 45.1%; p=0.057), more T3/T4 tumors (90.9% vs 84.3%; p<0.001), a greater number of poorly differentiated (G3) tumors (28.3% vs 24.2%; p=0.039), and more right side tumors (40.9% vs 26.6%; p <0.001).
In an abstract presented to the 2020 Virtual Congress of the European Society for Medical Oncology (abstract 399O), the investigators -- led by Sara Lonardi, MD, of the Veneto Institute of Oncology in Padua, Italy -- reported that median follow-up was 62.5 months for patients younger than 70 and 60.6 months for their counterparts over 70 years of age.
With respect to the trial’s primary endpoint, the researchers found that a greater proportion of older patients experienced relapse (24.2% vs 20.3%; p=0.033). Univariate analysis revealed a 27% increased risk of relapse among older patients (hazard ratio 1.27; p=0.011).
A greater proportion of total dose reductions (46.7% vs 41.4%; p=0.018) and treatment interruptions (26.1% vs 19.3%; p<0.001) were also observed among the older patients.
The investigators also performed a multivariable analysis of relapse-free interval, which adjusted for sex, ECOG status, tumor site, tumor stage, tumor grade, treatment, treatment duration, and dose reduction. Although this analysis did not find age to be a statistically significant factor in relapse-free survival (p=0.082), the authors noted that “the point estimate is not negligible,” with a hazard ratio of 1.19.
The only factor found to have a significant impact on relapse-free interval in this analysis was stage-III high-risk colorectal cancer (HR vs low-risk colorectal cancer: 2.05; p<0.001).
In light of these findings, Dr. Lonardi and her colleagues concluded that elderly stage-III colon cancer patients demonstrate different tolerability and potential reduced benefit to oxaliplatin-fluoropyrimidines adjuvant treatment.
“On the basis of these observations,” Dr. Lonardi said, “oxaliplatin-based based adjuvant chemotherapy should not be a priori denied to patients aged 70 years or more, but a careful evaluation of prognostic factors and expected compliance should be done case-by-case.”