Sequential treatment with regorafenib and trifluridine/tipiracil in later-line refractory metastatic colorectal cancer: A real-world multicenter retrospective study.

Abstract

45 Background: Regorafenib (R) and Trifluridine/tipiracil (T) have been shown to prolong survival for patients (pts) with refractory metastatic colorectal cancer (mCRC) but it's to date unclear which agent should be administered first. Our analysis aimed to compare the efficacy and safety profiles of these drugs sequentially administered in daily clinical practice. Methods: Clinical data of pts diagnosed with mCRC who received R and/or T between July 2012 and March 2022, were retrospectively collected from 12 institutes in Lazio Region. Overall survival (OS), progression-free survival (PFS), overall response rate (ORR), disease control rate (DCR), and adverse events (AEs) were compared between the two groups. Results: 781 pts were included. Of these, 270 (34.5%) received T alone, 278 (35.5%) R alone, 124 (15.8%) T followed by R, and 109 (13.9%) the reverse sequence. M/F = 452/329; median age was 68 (42-86); median duration of follow-up was 24.7 months (mos) (95%CI = 19.7-81.1). The prevalent ECOG PS was 1 (54%). We focused our attention on 233 pts who received R/T (N = 110, 14%) or T/R sequence (N = 123, 15.7%). ≥2 metastatic sites prevailed in both groups (83% T/R, 88% R/T; p = 0.45). Drug dose reductions due to grade 3/4 AEs were carried out in 81.8% of the R/T-treated pts (the R dose reduction to 120 mg and the T dose reduction to 30 mg/m2 were both the most prevalent in 28.8% of the cases) vs. 77.2% of the reverse sequence (R dose reduction to 120 mg was the most prevalent in 34.7% of the events) (p = 0.42). 143 pts (61.3%) experienced grade 3-4 toxicities (50.3% in R/T vs. 49.6% in T/R). The most common grade 3/4 AEs related to the R/T group were non-haematologic like hand-foot syndrome (21.6%) and fatigue (15.4%); on the other hand, these were haematologic: neutropenia (36.4%) and anemia (13%) (p = 0.28). Only 1 pt discontinued T in the T/R group. No therapy-related death was reported. The median PFS and OS of R/T were longer than the T/R sequence: 11 vs. 8,5 mos (HR = 0,62; 95%CI = 0,46-0,83; p = 0.0014) and 14,9 vs. 13 mos (HR = 0,70; 95%CI = 0,51-0,96; p = 0.0296), respectively. The ORR did not differ significantly showing slightly higher in the T/R sequence (4.8% vs. 2.2%; p = 0.45). The DCR was in favor of the R/T group (44.4% vs. 33.9%; p = 0.14). Conclusions: In our real-world context, PFS and OS were significantly longer in the R/T group. R and T used sequentially could extend survival and stabilize cancer growth without acting on tumor shrinkage. Safety profiles are in line with published data. Dose reductions were more frequent in the R/T group. We suggest that prospective clinical trials directly comparing R and T are needed.

Retrospective Correlation between First Drug Treatment Duration and Survival Outcomes in Sequential Treatment with Regorafenib and Trifluridine/Tipiracil in Refractory Metastatic Colorectal Cancer: A Real-World Subgroup Analysis

“…Though this is only conjecture, it is possible that this is because this group includes more than half of the patients in the two 3 to <6 months sequences. The results we came to in our earlier articles [16,19,31] are further supported by this finding. However, the lack of benefit seen in the <3 months and ≥6 months groups may be explained by the limited sample sizes of patients.…”

“…In line with our previous research, we tried to investigate T and R treatment sequencing further, for metastatic colorectal cancer that had relapsed or was refractory [16,19]. We hypothesized that therapy with R prior to that with T could result in improved survival results compared to reverse sequencing, based on interesting data from our previous real-world experience [31].…”

Treatment Settings and Outcomes with Regorafenib and Trifluridine/Tipiracil at Third-Line Treatment and beyond in Metastatic Colorectal Cancer: A Real-World Multicenter Retrospective Study

“…The best protocols for the administration of T and R in patients with advanced disease, the identification of subpopulations that might benefit from vital treatment with these drugs, and the identification of those subpopulations that might benefit from treatment with these drugs vs. the best supportive therapy alone are all questions that have yet to be resolved [ 29 , 30 , 31 , 32 , 33 , 34 , 35 ]. Furthermore, T and R have not been directly compared to one another, and it is uncertain which agent should be given first [ 36 , 37 , 38 , 39 , 40 , 41 ]. This multi-institutional retrospective study aimed to assess the effect of R and T, administered sequentially or not, on clinical outcomes and safety in patients with mCRC resistant to conventional chemotherapies.…”