Profile of trifluridine/tipiracil hydrochloride in the treatment of metastatic colorectal cancer: efficacy, safety, and place in therapy

Figures & data

Table 1 Comparison of Phase III trials evaluating TAS-102 and regorafenib

Trial	RECOURSE	CORRECT
	TAS-102 vs placebo	Regorafenib vs placebo
N	534 vs 266	505 vs 255
Median PFS (months)	2.0 vs 1.7	1.9 vs 1.7
HR (95% CI)	0.48 (0.41–0.57)	0.49 (0.42–0.58)
Median OS (months)	7.1 vs 5.3	6.4 vs 5.0
HR (95% CI)	0.68 (0.58–0.81)	0.77 (0.64–0.94)
Any grade AEs (%)	98 vs 93	93 vs 61
Grade 3–4 AEs (%)	69 vs 52	54 vs 14
Most relevant AEs	Neutropenia, anemia, nausea, appetite loss	Hand–foot skin reaction, rash, fatigue, hypertension

Abbreviations: PFS, progression-free survival; HR, hazard ratio; CI, confidence interval; OS, overall survival; AEs, adverse events.

Table 2 Retrospective studies evaluating TAS-102 and regorafenib as salvage-line treatment

Study	Masuishi et al^Citation19		Sueda et al^Citation22		REGOTAS^Citation23
Treatment	TAS-102	Regorafenib	TAS-102	Regorafenib	TAS-102	Regorafenib
N	50	146	14	23	327	223
Response rate	0%	0.8%	0%	0%
Disease control rate	38%	33%	29%	30%
	P=0.60
Median PFS	2.1 months 95% CI 1.8–3.1	2.1 months 95% CI 1.8–2.5	2.1 months 95% CI 0.92–6.39	3.0 months 95% CI 1.64–4.52	2.1 months 95% CI 2.0–2.3	2.1 months 95% CI 2.0–2.4
	HR 1.20 95% CI 0.87–1.67 P=0.27		P=0.59
	Adjusted HR 1.27 95% CI 0.90–1.83 P=0.18				Adjusted HR 0.94 P=0.54
Median OS	6.5 months 95% CI 5.3–8.3	6.7 months 95% CI 5.8–7.6	6.3 months 95% CI 3.21–9.93	5.8 months 95% CI 3.7–11.7	7.4 months 95% CI 6.8–8.3	7.9 months 95% CI 6.8–9.2
	HR 1.01 95% CI 0.70–1.49 P=0.97		P=0.60
	Adjusted HR 0.98 95% CI 0.65–1.51 P=0.92				Adjusted HR 0.96 95% CI 0.78–1.18 P=0.69
Subsequent chemotherapy	44%	54%			50%	65%
TAS-102	0%	30%	0%	26%	0%	59%
Regorafenib	28%	0%	57%	0%	37%	0%
Reason for treatment discontinuation
Disease progression	94%	86%	86%	61%	92%	75%
Adverse events	6%	12%	14%	26%	7%	24%

Abbreviations: PFS, progression-free survival; HR, hazard ratio; OS, overall survival; CI, confidence interval.

Table 3 Ongoing clinical trials evaluating TAS-102 regimens

Triala	Phase	Trial ID	Treatment
First line
ALEXANDRIA	II	NCT02654639	TAS-102 with bevacizumab maintenance therapy post-induction chemo
TASCO1	II	NCT02743221	TAS-102 plus bevacizumab vs capecitabine plus bevacizumab for patients non-eligible for intensive chemo
KSCC1602	1	UMIN000025241	TAS-102 plus bevacizumab for the elderly
Second line
TRUSTY	II	JapicCTI-173618	TAS plus bevacizumab vs FOLFIRI plus bevacizumab
T-CORE	II	UMIN000017589	TAS-102 alone for the elderly
MODURATE	1	UMIN000019828	TAS-102 plus irinotecan with bevacizumab
CL1-95005-001	1	NCT02848443	TAS-102 plus oxaliplatin (± bevacizumab or nivolumab)
TAS-102-109	1	NCT01916447	TAS-102 plus irinotecan with bevacizumab
Salvage line
WJOG8916G	II	UMIN000027210	TAS-102 plus cetuximab for RAS wild-type patients refractory to previous anti-EGFR antibodies
TAS-102-203 study	1	NCT02860546	TAS-102 plus nivolumab for patients with MSS CRC
TAS-OX	1/II	NCT02848079	TAS-102 plus oxaliplatin
APOLLON	1/II	NCT02613221	TAS-102 plus panitumumab
N-TASK FORCE	1/II	UMIN000017114	TAS-102 plus nintedanib

Note:

a No references are available for these ongoing trials.

Abbreviations: FOLFIRI, fluorouracil/levofolinate calcium plus irinotecan; EGFR, epidermal growth factor receptor; MSS, microsatellite stable; CRC, colorectal cancer.

MasuishiTTaniguchiHHamauchiSRegorafenib versus trifluridine/tipiracil for refractory metastatic colorectal cancer: a retrospective comparisonClin Colorectal Cancer2017162e15e2227670892

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SuedaTSakaiDKudoTEfficacy and safety of regorafenib or TAS-102 in patients with metastatic colorectal cancer refractory to standard therapiesAnticancer Res20163684299430627466548

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FukuokaSMoriwakiTTaniguchiHRegorafenib (REG) versus trifluridine/tipiracil (TAS-102) as salvage-line in patients with metastatic colorectal cancer refractory to standard chemotherapies (REGOTAS): a propensity score analysis from a JSCCR multicenter observational studyJ Clin Oncol20173515 Suppl3540

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