The objective of the study is to compare the effectiveness of various systemic therapies in the 3rd and subsequent lines of treatment.

Materials and methods. Retrospective multicenter study collected data from 2 clinics of the Russian Federation. We considered overall survival (OS) as the main criterion of effectiveness. Progression-free survival (PFS) was the additional criterion. We performed a single- and multifactorial analysis of the effect of various parameters on PFS. To evaluate the effectiveness of regorafenib and the reintroduction of previously effective drugs, we should prove the equivalence of reintroduction of the 3rd line chemotherapy and targeted therapy to regorafenib on the 6-month overall survival, provided that the equivalence boundaries would be between 0.8 to 1.25. To reach the 0.05 probability of type I error and the 80% study power, 178 patients (89 in each group) should be included in the study.

Results. The database identified 215 patients with morphologically confirmed metastatic colon cancer who received two or more lines of antitumor drug therapy from 2010 to 2021. We selected 132 patients with the history of regorafenib therapy and 83 patients with the reintroduction of a previously used chemotherapy regimen as 3rd line treatment. The median OS in the reintroduction and regorafenib groups did not differ (hazard ratio [HR], 1.01; 95% CI, 0.7–1.45; p=0.920); 6-month OS were 74 and 70%, respectively. Progression-free survival was significantly higher in the reintroduction group (HR, 1.94; 95% CI, 1.3–2.7; p<0.001). Multivariate analysis showed that the reintroduction of previous treatment regimens kept its independent positive effect on progression-free survival (HR, 1.9; 95% CI, 1.3–2.8; p<0.001). In our study, toxicity on the 3rd line of CT developed in 117 (54.4%) of 215 patients and significantly more frequent in the regorafenib group: 67.4% (89/132) versus 33.7% (28/83) in the group with repeated administration of previously effective regimens (p<0.001). 

Conclusions: regorafenib and reintroduction of the previous treatment in the 3rd line did not differ in overall survival. Progression-free survival was significantly higher in the reintroduction group as the 3rd line of treatment, with significantly lower toxicity. 

Key words: colon cancer, chemotherapy, regorafenib, chemotherapy, retrospective study.