Summary

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• This summary is based on the review of six systematic review(s)/meta-analysis(es). ^[1-6]
• In metastatic colorectal cancer (mCRC), the addition of bevacizumab to trifluridine/tipiracil significantly improved overall survival (OS), with hazard ratios reported as 0.61 (95% CI (confidence interval) 0.52-0.70, p < 0.001) and 0.41 (95% CrI 0.32-0.52) compared to best supportive care (BSC). Median OS for the combination was reported between 8.6 and 14.4 months, with a consistent benefit observed across various subgroups, including those with KRAS mutations.
• Progression-free survival (PFS) was also significantly higher with the combination, as shown by a hazard ratio of 0.52 (95% CI 0.42-0.63, p < 0.001) and a median PFS range of 3.7-6.8 months. This improvement was observed across patient subgroups irrespective of KRAS mutation status, with a median PFS of 4.2 months for the combination versus 2.6 months for monotherapy.
• The combination treatment significantly improved the objective response rate (ORR) and disease control rate (DCR) compared to trifluridine/tipiracil alone, with an ORR risk ratio of 3.14 (95% CI 1.51-6.51, p = 0.002) and a DCR risk ratio of 1.66 (95% CI 1.28-2.16, p = 0.0001), reaching an absolute DCR of 64% with the combination versus 43% with monotherapy.
• The combination of trifluridine/tipiracil with bevacizumab was associated with a higher rate of neutropenia compared to monotherapy, with reported grade ≥3 neutropenia rates ranging from 29%-67% in combination therapy versus 5%-41% in monotherapy (RR 1.38; 95% CI 1.19-1.59; p = 0.00001). One study indicated grade ≥3 neutropenia at 43% for combination therapy compared to 29% for monotherapy.
• Other adverse events included anemia, which was more common in monotherapy (RR (relative risk) 0.60; 95% CI 0.44-0.82; p = 0.001), and similar rates of febrile neutropenia, fatigue, diarrhea, nausea, and vomiting between the combination and monotherapy groups, with incidence rates between 1%-7%. Discontinuation rates due to adverse events were low, reported at 8% for the combination and 7% for monotherapy.
• Subgroup analyses indicate that the combination of TAS-102 (trifluridine/tipiracil) and bevacizumab is highly ranked for efficacy across age, gender, ECOG (Eastern Cooperative Oncology Group) performance status, and time from initial mCRC diagnosis, as highlighted in one study using Bayesian SUCRA (Surface Under the Cumulative Ranking Curve).
• The survival benefits of trifluridine/tipiracil with or without bevacizumab were consistent across KRAS mutation statuses, including codons 12 and 13, indicating that the treatment efficacy remains unaffected by KRAS mutation variations, as reported in another study.