Influence of age on disease control rate of patients treated with regorafenib and trifluridine/tipiracil in refractory metastatic colorectal cancer: A multicenter retrospective real-world study

As society ages, the number of elderly patients with refractory metastatic colorectal cancer (mCRC) will increase. However, older people (≥ 70 years) have rarely been the focus of studies on CRC. The purpose of this study was to compare the effect of age on disease control in this subset of patients to younger patients receiving regorafenib (R) and trifluridine/tipiracil therapy (T). The disease control rate (DCR) was calculated as the sum of the rates of complete, partial, and stable disease, assessed using RECIST criteria, and was compared according to whether the two drugs were administered sequentially or not. Clinical data of patients diagnosed with mCRC treated with R and/or T between 2012 and 2022, were retrospectively collected from 13 Italian cancer centers. 866 patients who received sequential R and T (T/R, n=146 [16.8%]; R/T, n=116 [13.3%]) or T (n=325 [37.5%]) or R (n=279 [32.2%]) only, were retrospectively recruited. We focused on patients who were ≥ 70 years old (109 patients [12.5%] in the sequential groups and 275 patients [31.7%] in the single-agent groups) and we compared them to the < 70 years old patients (153 [17.6%] in the T/R and R/T groups vs. 329 [37.9%] of T and R groups). In the sequential treatment cohorts, we observed a statistically significant 48.5% of disease control rate in ≥70 years old patients (N=79) treated with R/T (48.5%) vs. 26.3% of ≥70 years old patients (N=67) treated with T/R, vs. 41.2% of the patients younger than 70 years (N=42) in the T/R group and vs. 47.5% noted in < 70 years aged patients (N=74) treated with the R/T sequence (p=0.0035). Regarding the non-sequential treatment cohorts, we found a statistically significant advantage, albeit small, of 23.6% in favor of < 70 years old patients (N=96) who were administered T, 23.1% of patients (N=172) who were almost 70 years old in the T group too, 22.4% of < 70 years old cases treated with R (N=181) and finally, 20.4% of ≥ 70 years old patients (N=147) in the R group (p=0.0487). In an attempt to investigate the therapeutic approaches with R and T in routine clinical practice and the benefits and drawbacks of sequential or non-sequential treatments with these two agents, our retrospective study confirmed that, alongside survival outcomes, disease control is likewise a crucial element even in the elderly patient in late-line refractory mCRC.