Clinical advances in later-line therapy for metastatic or refractory colorectal cancer

Table 1 Later-line treatment studies of trifluridine/tipiracil hydrochloride mixture

Trial name/Ref.	Regimen	Sample size	Dosage and administration (experimental group)	mPFS (months, 95%CI)	Hazard ratio (95%CI), P value	mOS (months, 95%CI)	Hazard ratio (95%CI), P value	ORR (%), P value
Mayer et al[9], 2015	TAS-102 vs placebo	800	TAS-102: 35 mg/m2 bid, days 1–5 and 8–12, q28d	2.0 (1.9–2.1) vs 1.7 (1.7–1.8)	0.48 (0.41–0.57); P < 0.001	7.1 (6.5–7.8) vs 5.3 (4.6–6.0)	0.68 (0.58-0.81); P < 0.001	1.6 vs 0.4; P = 0.29
Martínez-Lago et al[11], 2022	TAS-102 + bevacizumab	35	TAS-102: 30–35 mg/m2 bid, days 1–5 and 8–12, q28d; bevacizumab: 5 mg/kg, q14d	4.3 (3.4–5.1)		9.3 (6.6–12.1)		3.20%
TAS-CC4 study[12], 2022	TAS-102 + bevacizumab	44	TAS-102: 35 mg/m2 bid, days 1–5 and 15–19, q28d; bevacizumab: 5 mg/kg, q14d	4.6 (3.6–5.3)		10.5 (9.6–11.4)		4.50%
E-BiTS study[13], 2025	TAS-102 + bevacizumab	33	TAS-102: 35 mg/m2 bid, days 1–5, q14d1; bevacizumab: 5 mg/kg q14d	5.6 (2.7–6.5)		17.6 (10.1–not available)		9.10%
Kuboki et al[14], 2023	TAS-102 + bevacizumab vs FOLFIRI + bevacizumab	397	TAS-102: 35 mg/m2 bid, days 1–5 and 8–12, q28d; bevacizumab: 5 mg/kg, q14d	4.5 (3.8–5.8) vs 6.0 (5.6–6.7)	1.45 (1.14–1.84)	14.8 (12.6–19.1) vs 18.1 (16.0–23.2)	1.38 (0.99-1.93); P = 0.5920	3.8% vs 7.1%; P = 0.2498
Li et al[15], 2024	TAS-102 + bevacizumab + irinotecan	35	TAS-102: 30 mg/m2 bid, days 1–5, q14d; bevacizumab: 5 mg/kg, q14d; irinotecan: 150 mg/m2, q14d	9.2 (6.285–12.115)				25.80%
Yang et al[16], 2026	TAS-102 + bevacizumab + irinotecan	60	TAS-102: 30 mg/m2 bid, days 1–5, q14d; bevacizumab: 5 mg/kg, q14d; irinotecan: 150 mg/m2 q14d	6.6 (4.39–8.81)		17.3 (13.55–21.05)		18.30%
Bordonaro et al[18], 2021	TAS-102 + oxaliplatin + bevacizumab vs TAS-102 + oxaliplatin + nivolumab	54	TAS-102: 35 mg/m2 bid, days 1–5, q14d; oxaliplatin: 85 mg/m2, q14d; bevacizumab: 5 mg/kg; nivolumab: 3 mg/kg, q14d	6.3 (5.5–15.6) vs 6.0 (2.0–8.0)		15.1 (10.7–NR) vs NR (6.5–NR)		17.1% vs 7.1%
Napolitano et al[20], 2023	TAS-102 + panitumumab vs TAS-102	62	TAS-102: 35 mg/m2 bid, days 1–5 and 8–12, q28d; panitumumab: 6 mg/kg days 1 and 15, q28d	4.0 (2.8–5.3)	0.48 (0.28–0.82); P = 0.007

¹Escalated by 10 mg/day per cycle, up to a maximum of 30 mg/day, during cycles 2–4.

CI: Confidence interval; mOS: Median overall survival; mPFS: Median progression-free survival; NR: Not reached; ORR: Objective response rate; TAS-102: Trifluridine/tipiracil hydrochloride mixture.