A Study Evaluating S 95005 Plus Bevacizumab and Capecitabine Plus Bevacizumab in Patients With Previously Untreated Colorectal Cancer Who Are Non-eligible for Intensive Therapy (TASCO1)

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ClinicalTrials.gov Identifier: NCT02743221

Recruitment Status : Completed

First Posted : April 19, 2016

Results First Posted : April 16, 2019

Last Update Posted : October 5, 2021

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Sponsor:

Collaborator:

ADIR, a Servier Group company

Information provided by (Responsible Party):

Servier ( Institut de Recherches Internationales Servier )

Study Type	Interventional
Study Design	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
Condition	Metastatic Colorectal Cancer
Interventions	Drug: Trifluridine/tipiracil + bevacizumab Drug: Capecitabine + bevacizumab
Enrollment	154

Participant Flow

Recruitment Details
Pre-assignment Details	154 patients were randomized among whom one was deemed ineligible after randomization.


Arm/Group Title	Trifluridine/Tipiracil + Bevacizumab	Capecitabine + Bevacizumab
Arm/Group Description	Trifluridine/tipiracil (S95005): fi...	Capecitabine was administered at 12...
Arm/Group Description	Trifluridine/tipiracil (S95005): film-coated tablets containing 15mg of trifluridine and 7.065mg of tipiracil hydrochloride, or 20mg of trifluridine and 9.42mg of tipiracil hydrochloride. Bevacizumab: concentrate for solution for IV infusion containing 25mg/ml of bevacizumab. Trifluridine/tipiracil was administered at 35 mg/m2/dose orally within 1 hour after completion of morning and evening meals, for 5 days on/2 days off, over 2 weeks, followed by a 14-day rest period, with bevacizumab administered intravenously at the dose of 5 mg/kg every 2 weeks at Day 1 and Day 15.This treatment cycle was repeated every 4 weeks. Trifluridine/tipiracil + bevacizumab: Patients were treated withTrifluridine/tipiracil + bevacizumab regimen until they met a discontinuation criterion.	Capecitabine was administered at 1250 mg/m² orally BID on Days 1-14 of each cycle, with bevacizumab (7.5 mg/kg, IV) administered on Day 1 of each cycle. This treatment cycle was repeated every 3 weeks Capecitabine + bevacizumab: Patients were treated with capecitabine+ bevacizumab regimen until they met a discontinuation criterion.
Period Title: Overall Study
Started	77	77
Completed ^[1]	21	17
Not Completed	56	60
Reason Not Completed
Progressive disease	29	38
Adverse Event	17	14
non medical reason	8	2
Physician Decision	2	5
Patient not eligible, not treated	0	1
[1] Of note, these patients were still under treatment at the primary completion date (cut-off date).

Baseline Characteristics

Arm/Group Title		Trifluridine/Tipiracil + Bevacizumab	Capecitabine + Bevacizumab	Total
Arm/Group Description		Trifluridine/tipiracil (S95005): fi...	Capecitabine was administered at 12...	Total of all reporting groups
Arm/Group Description		Trifluridine/tipiracil (S95005): film-coated tablets containing 15mg of trifluridine and 7.065mg of tipiracil hydrochloride, or 20mg of trifluridine and 9.42mg of tipiracil hydrochloride. Bevacizumab: concentrate for solution for IV infusion containing 25mg/ml of bevacizumab. Trifluridine/tipiracil was administered at 35 mg/m2/dose orally within 1 hour after completion of morning and evening meals, for 5 days on/2 days off, over 2 weeks, followed by a 14-day rest period, with bevacizumab administered intravenously at the dose of 5 mg/kg every 2 weeks at Day 1 and Day 15.This treatment cycle was repeated every 4 weeks. Trifluridine/tipiracil + bevacizumab: Patients were treated withTrifluridine/tipiracil + bevacizumab regimen until they met a discontinuation criterion.	Capecitabine was administered at 1250 mg/m² orally BID on Days 1-14 of each cycle, with bevacizumab (7.5 mg/kg, IV) administered on Day 1 of each cycle. This treatment cycle was repeated every 3 weeks Capecitabine + bevacizumab: Patients were treated with capecitabine+ bevacizumab regimen until they met a discontinuation criterion.	Total of all reporting groups
Overall Number of Baseline Participants		77	77	154
Baseline Analysis Population Description		[Not Specified]
Baseline Analysis Population Description		[Not Specified]
Age, Categorical Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	77 participants	77 participants	154 participants
	<=18 years	0 0.0%	0 0.0%	0 0.0%
	Between 18 and 65 years	20 26.0%	16 20.8%	36 23.4%
	>=65 years	57 74.0%	61 79.2%	118 76.6%
Age, Continuous Mean (Standard Deviation) Unit of measure: Years
	Number Analyzed	77 participants	77 participants	154 participants
		69.8 (10.2)	72.8 (11.0)	71.3 (10.7)
Sex: Female, Male Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	77 participants	77 participants	154 participants
	Female	37 48.1%	29 37.7%	66 42.9%
	Male	40 51.9%	48 62.3%	88 57.1%
Race/Ethnicity, Customized Measure Type: Count of Participants Unit of measure: Participants	Number Analyzed	77 participants	77 participants	154 participants
White		73 94.8%	72 93.5%	145 94.2%
Asian		1 1.3%	2 2.6%	3 1.9%
Other		1 1.3%	1 1.3%	2 1.3%
Not collected		2 2.6%	2 2.6%	4 2.6%

Outcome Measures

1.Primary Outcome


Title	Progression Free Survival (PFS)
Description	The progression free survival (PFS), defined as the time from the date...
Description	The progression free survival (PFS), defined as the time from the date of randomisation until the date of the investigator-assessed radiological disease progression or death due to any cause according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Progressive disease (PD) was defined at least a 20% increase in the sum of diameters of target lesions (taking as reference the smallest sum on study) and an absolute increase of at least 5 mm in the sum of lesions or the appearance of new lesions.
Time Frame	Baseline and every 8 weeks (maximum follow-up duration: 17.9 months)

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS): all randomised patients who have taken at least one dose of study treatment.


Arm/Group Title	Trifluridine/Tipiracil + Bevacizumab	Capecitabine + Bevacizumab
Arm/Group Description:	Trifluridine/tipiracil (S95005): fi...	Capecitabine was administered at 12...
Arm/Group Description:	Trifluridine/tipiracil (S95005): film-coated tablets containing 15mg of trifluridine and 7.065mg of tipiracil hydrochloride, or 20mg of trifluridine and 9.42mg of tipiracil hydrochloride. Bevacizumab: concentrate for solution for IV infusion containing 25mg/ml of bevacizumab. Trifluridine/tipiracil was administered at 35 mg/m2/dose orally within 1 hour after completion of morning and evening meals, for 5 days on/2 days off, over 2 weeks, followed by a 14-day rest period, with bevacizumab administered intravenously at the dose of 5 mg/kg every 2 weeks at Day 1 and Day 15.This treatment cycle was repeated every 4 weeks. Trifluridine/tipiracil + bevacizumab: Patients were treated withTrifluridine/tipiracil + bevacizumab regimen until they met a discontinuation criterion.	Capecitabine was administered at 1250 mg/m² orally BID on Days 1-14 of each cycle, with bevacizumab (7.5 mg/kg, IV) administered on Day 1 of each cycle. This treatment cycle was repeated every 3 weeks Capecitabine + bevacizumab: Patients were treated with capecitabine+ bevacizumab regimen until they met a discontinuation criterion.
Overall Number of Participants Analyzed	77	76
Median (95% Confidence Interval) Unit of Measure: months
	9.2 (7.6 to 11.6)	7.8 (5.5 to 10.2)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Trifluridine/Tipiracil + Bevacizumab, Capecitabine + Bevacizumab
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	This was a non-comparative study.

Statistical Test of Hypothesis	P-Value	0.09
	Comments	[Not Specified]
	Method	Cox proportional hazard model
	Comments	Cox proportional hazard model with adjustment for the stratification factors (RAS status, performance status ECOG)

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.71
	Confidence Interval	(2-Sided) 95% 0.48 to 1.06
	Estimation Comments	[Not Specified]

2.Secondary Outcome


Title	Overall Response Rate (ORR)
Description	As per RECIST v1.1, Complete Response (CR) was disappearance of all ta...
Description	As per RECIST v1.1, Complete Response (CR) was disappearance of all target lesions; Partial Response (PR) was at least 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. The ORR was the proportion of patients who presented CR or PR with confirmation at subsequent time point or at least 4 weeks later.
Time Frame	Baseline and every 8 weeks (maximum follow-up duration: 17.9 months)

Outcome Measure Data

Analysis Population Description

FAS


Arm/Group Title	Trifluridine/Tipiracil + Bevacizumab	Capecitabine + Bevacizumab
Arm/Group Description:	Trifluridine/tipiracil (S95005): fi...	Capecitabine was administered at 12...
Arm/Group Description:	Trifluridine/tipiracil (S95005): film-coated tablets containing 15mg of trifluridine and 7.065mg of tipiracil hydrochloride, or 20mg of trifluridine and 9.42mg of tipiracil hydrochloride. Bevacizumab: concentrate for solution for IV infusion containing 25mg/ml of bevacizumab. Trifluridine/tipiracil was administered at 35 mg/m2/dose orally within 1 hour after completion of morning and evening meals, for 5 days on/2 days off, over 2 weeks, followed by a 14-day rest period, with bevacizumab administered intravenously at the dose of 5 mg/kg every 2 weeks at Day 1 and Day 15.This treatment cycle was repeated every 4 weeks. Trifluridine/tipiracil + bevacizumab: Patients were treated withTrifluridine/tipiracil + bevacizumab regimen until they met a discontinuation criterion.	Capecitabine was administered at 1250 mg/m² orally BID on Days 1-14 of each cycle, with bevacizumab (7.5 mg/kg, IV) administered on Day 1 of each cycle. This treatment cycle was repeated every 3 weeks Capecitabine + bevacizumab: Patients were treated with capecitabine+ bevacizumab regimen until they met a discontinuation criterion.
Overall Number of Participants Analyzed	77	76
Measure Type: Count of Participants Unit of Measure: Participants
	26 33.8%	23 30.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Trifluridine/Tipiracil + Bevacizumab, Capecitabine + Bevacizumab
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.73
	Comments	[Not Specified]
	Method	Fisher Exact
	Comments	[Not Specified]

3.Secondary Outcome


Title	Duration of Response (DR)
Description	The DR was calculated among patients with CR or PR as the time (months...
Description	The DR was calculated among patients with CR or PR as the time (months) from the first documentation of response to the first documentation of objective tumor progression or death due to any cause, whichever occurred first.
Time Frame	Baseline and every 8 weeks (maximum follow-up duration: 16.6 months)

Outcome Measure Data

Analysis Population Description

Tumour Response population: patients with measurable disease at baseline and with at least one tumour evaluation while on treatment.


Arm/Group Title	Trifluridine/Tipiracil + Bevacizumab	Capecitabine + Bevacizumab
Arm/Group Description:	Trifluridine/tipiracil (S95005): fi...	Capecitabine was administered at 12...
Arm/Group Description:	Trifluridine/tipiracil (S95005): film-coated tablets containing 15mg of trifluridine and 7.065mg of tipiracil hydrochloride, or 20mg of trifluridine and 9.42mg of tipiracil hydrochloride. Bevacizumab: concentrate for solution for IV infusion containing 25mg/ml of bevacizumab. Trifluridine/tipiracil was administered at 35 mg/m2/dose orally within 1 hour after completion of morning and evening meals, for 5 days on/2 days off, over 2 weeks, followed by a 14-day rest period, with bevacizumab administered intravenously at the dose of 5 mg/kg every 2 weeks at Day 1 and Day 15.This treatment cycle was repeated every 4 weeks. Trifluridine/tipiracil + bevacizumab: Patients were treated withTrifluridine/tipiracil + bevacizumab regimen until they met a discontinuation criterion.	Capecitabine was administered at 1250 mg/m² orally BID on Days 1-14 of each cycle, with bevacizumab (7.5 mg/kg, IV) administered on Day 1 of each cycle. This treatment cycle was repeated every 3 weeks Capecitabine + bevacizumab: Patients were treated with capecitabine+ bevacizumab regimen until they met a discontinuation criterion.
Overall Number of Participants Analyzed	74	73
Median (80% Confidence Interval) Unit of Measure: months
	7.9 (6.01 to 14.75)	9.9 (8.41 to 10.02)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Trifluridine/Tipiracil + Bevacizumab, Capecitabine + Bevacizumab
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.16
	Confidence Interval	(2-Sided) 95% 0.49 to 2.74
	Estimation Comments	[Not Specified]

4.Secondary Outcome


Title	Disease Control Rate (DCR)
Description	DCR was the proportion of patients with confirmed CR, PR or stable dis...
Description	DCR was the proportion of patients with confirmed CR, PR or stable disease (SD) as best overall response. SD defined as neither sufficient decrease to qualify for PR nor sufficient increase to qualify for PD.
Time Frame	Baseline and every 8 weeks (maximum follow-up duration: 17.9 months)

Outcome Measure Data

Analysis Population Description

FAS


Arm/Group Title	Trifluridine/Tipiracil + Bevacizumab	Capecitabine + Bevacizumab
Arm/Group Description:	Trifluridine/tipiracil (S95005): fi...	Capecitabine was administered at 12...
Arm/Group Description:	Trifluridine/tipiracil (S95005): film-coated tablets containing 15mg of trifluridine and 7.065mg of tipiracil hydrochloride, or 20mg of trifluridine and 9.42mg of tipiracil hydrochloride. Bevacizumab: concentrate for solution for IV infusion containing 25mg/ml of bevacizumab. Trifluridine/tipiracil was administered at 35 mg/m2/dose orally within 1 hour after completion of morning and evening meals, for 5 days on/2 days off, over 2 weeks, followed by a 14-day rest period, with bevacizumab administered intravenously at the dose of 5 mg/kg every 2 weeks at Day 1 and Day 15.This treatment cycle was repeated every 4 weeks. Trifluridine/tipiracil + bevacizumab: Patients were treated withTrifluridine/tipiracil + bevacizumab regimen until they met a discontinuation criterion.	Capecitabine was administered at 1250 mg/m² orally BID on Days 1-14 of each cycle, with bevacizumab (7.5 mg/kg, IV) administered on Day 1 of each cycle. This treatment cycle was repeated every 3 weeks Capecitabine + bevacizumab: Patients were treated with capecitabine+ bevacizumab regimen until they met a discontinuation criterion.
Overall Number of Participants Analyzed	77	76
Measure Type: Count of Participants Unit of Measure: Participants
	66 85.7%	59 77.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Trifluridine/Tipiracil + Bevacizumab, Capecitabine + Bevacizumab
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.22
	Comments	[Not Specified]
	Method	Fisher Exact
	Comments	[Not Specified]

5.Secondary Outcome


Title	Overall Survival (OS)
Description	The OS was defined as the time from the date of randomisation to the d...
Description	The OS was defined as the time from the date of randomisation to the date of death. If death was not confirmed, or patient was alive at study cut-off date, survival time was censored at the date of last follow-up or at the study cut-off date, whichever was earlier.
Time Frame	Baseline up to death or study cut-off (maximum follow-up duration: 19.9 months)

Outcome Measure Data

Analysis Population Description

FAS


Arm/Group Title	Trifluridine/Tipiracil + Bevacizumab	Capecitabine + Bevacizumab
Arm/Group Description:	Trifluridine/tipiracil (S95005): fi...	Capecitabine was administered at 12...
Arm/Group Description:	Trifluridine/tipiracil (S95005): film-coated tablets containing 15mg of trifluridine and 7.065mg of tipiracil hydrochloride, or 20mg of trifluridine and 9.42mg of tipiracil hydrochloride. Bevacizumab: concentrate for solution for IV infusion containing 25mg/ml of bevacizumab. Trifluridine/tipiracil was administered at 35 mg/m2/dose orally within 1 hour after completion of morning and evening meals, for 5 days on/2 days off, over 2 weeks, followed by a 14-day rest period, with bevacizumab administered intravenously at the dose of 5 mg/kg every 2 weeks at Day 1 and Day 15.This treatment cycle was repeated every 4 weeks. Trifluridine/tipiracil + bevacizumab: Patients were treated withTrifluridine/tipiracil + bevacizumab regimen until they met a discontinuation criterion.	Capecitabine was administered at 1250 mg/m² orally BID on Days 1-14 of each cycle, with bevacizumab (7.5 mg/kg, IV) administered on Day 1 of each cycle. This treatment cycle was repeated every 3 weeks Capecitabine + bevacizumab: Patients were treated with capecitabine+ bevacizumab regimen until they met a discontinuation criterion.
Overall Number of Participants Analyzed	77	76
Median (80% Confidence Interval) Unit of Measure: months
	18.0 (15.18 to 19.48)	16.2 (13.07 to 17.67)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Trifluridine/Tipiracil + Bevacizumab, Capecitabine + Bevacizumab
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.04
	Comments	[Not Specified]
	Method	Cox proportional hazard model
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.56
	Confidence Interval	(2-Sided) 95% 0.32 to 0.98
	Estimation Comments	[Not Specified]

Adverse Events

Time Frame	All Adverse Events (AE) were collected from the informed consent signature up to the final visit regardless of seriousness or relationship to study drug (maximum exposure: 82 weeks).
Adverse Event Reporting Description	Reported AEs are Treatment-Emergent AEs (TEAE) that are AEs that developed/worsened during the treatment period i.e. between the first treatment intake date and the last treatment intake date + 35 days. In the Capecitabine + bevacizumab group, the number of participants at Risk for TEAE (both serious and non-serious) was 76 which is different from Started patients in the Participant Flow module (=77). Indeed, 1 started patient in this group did not received any treatment dose

Arm/Group Title	Trifluridine/Tipiracil + Bevacizumab		Capecitabine + Bevacizumab
Arm/Group Description	Trifluridine/tipiracil (S95005): fi...		Capecitabine was administered at 12...
Arm/Group Description	Trifluridine/tipiracil (S95005): film-coated tablets containing 15mg of trifluridine and 7.065mg of tipiracil hydrochloride, or 20mg of trifluridine and 9.42mg of tipiracil hydrochloride. Bevacizumab: concentrate for solution for IV infusion containing 25mg/ml of bevacizumab. Trifluridine/tipiracil was administered at 35 mg/m2/dose orally within 1 hour after completion of morning and evening meals, for 5 days on/2 days off, over 2 weeks, followed by a 14-day rest period, with bevacizumab administered intravenously at the dose of 5 mg/kg every 2 weeks at Day 1 and Day 15.This treatment cycle was repeated every 4 weeks. Trifluridine/tipiracil + bevacizumab: Patients were treated withTrifluridine/tipiracil + bevacizumab regimen until they met a discontinuation criterion.		Capecitabine was administered at 1250 mg/m² orally BID on Days 1-14 of each cycle, with bevacizumab (7.5 mg/kg, IV) administered on Day 1 of each cycle. This treatment cycle was repeated every 3 weeks Capecitabine + bevacizumab: Patients were treated with capecitabine+ bevacizumab regimen until they met a discontinuation criterion.
All-Cause Mortality
	Trifluridine/Tipiracil + Bevacizumab		Capecitabine + Bevacizumab
	Affected / at Risk (%)		Affected / at Risk (%)
Total	22/77 (28.57%)		33/76 (43.42%)
Serious Adverse Events Serious Adverse Events
	Trifluridine/Tipiracil + Bevacizumab		Capecitabine + Bevacizumab
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	42/77 (54.55%)		44/76 (57.89%)
Blood and lymphatic system disorders
Anaemia ^† 1	3/77 (3.90%)	4	0/76 (0.00%)	0
Febrile neutropenia ^† 1	3/77 (3.90%)	3	3/76 (3.95%)	3
Haemorrhagic anaemia ^† 1	1/77 (1.30%)	1	0/76 (0.00%)	0
Neutropenia ^† 1	4/77 (5.19%)	5	0/76 (0.00%)	0
Cardiac disorders
Acute coronary syndrome ^† 1	1/77 (1.30%)	1	0/76 (0.00%)	0
Atrial fibrillation ^† 1	1/77 (1.30%)	1	1/76 (1.32%)	1
Atrioventricular block complete ^† 1	0/77 (0.00%)	0	1/76 (1.32%)	1
Mitral valve incompetence ^† 1	1/77 (1.30%)	1	0/76 (0.00%)	0
Myocardial infarction ^† 1	2/77 (2.60%)	2	0/76 (0.00%)	0
Supraventricular tachycardia ^† 1	0/77 (0.00%)	0	1/76 (1.32%)	1
Ventricular tachycardia ^† 1	1/77 (1.30%)	1	0/76 (0.00%)	0
Endocrine disorders
Hypothyroidism ^† 1	0/77 (0.00%)	0	1/76 (1.32%)	1
Gastrointestinal disorders
Ascites ^† 1	1/77 (1.30%)	1	0/76 (0.00%)	0
Diarrhoea ^† 1	2/77 (2.60%)	2	5/76 (6.58%)	5
Enterocutaneous fistula ^† 1	1/77 (1.30%)	1	0/76 (0.00%)	0
Gastrointestinal angiodysplasia haemorrhagic ^† 1	1/77 (1.30%)	1	0/76 (0.00%)	0
Haematemesis ^† 1	1/77 (1.30%)	1	0/76 (0.00%)	0
Ileus paralytic ^† 1	0/77 (0.00%)	0	1/76 (1.32%)	1
Intestinal obstruction ^† 1	2/77 (2.60%)	2	1/76 (1.32%)	1
Intestinal perforation ^† 1	1/77 (1.30%)	1	0/76 (0.00%)	0
Large intestinal obstruction ^† 1	0/77 (0.00%)	0	1/76 (1.32%)	1
Large intestine perforation ^† 1	1/77 (1.30%)	1	1/76 (1.32%)	1
Malignant bowel obstruction ^† 1	0/77 (0.00%)	0	2/76 (2.63%)	2
Nausea ^† 1	1/77 (1.30%)	1	1/76 (1.32%)	1
Pancreatitis ^† 1	1/77 (1.30%)	1	0/76 (0.00%)	0
Proctalgia ^† 1	1/77 (1.30%)	1	0/76 (0.00%)	0
Small intestinal obstruction ^† 1	1/77 (1.30%)	1	1/76 (1.32%)	1
Umbilical hernia ^† 1	1/77 (1.30%)	1	0/76 (0.00%)	0
Vomiting ^† 1	2/77 (2.60%)	4	1/76 (1.32%)	1
General disorders
Death ^† 1	0/77 (0.00%)	0	2/76 (2.63%)	2
General physical health deterioration ^† 1	0/77 (0.00%)	0	2/76 (2.63%)	2
Mucosal dryness ^† 1	0/77 (0.00%)	0	1/76 (1.32%)	1
Multiple organ dysfunction syndrome ^† 1	0/77 (0.00%)	0	1/76 (1.32%)	1
Non-cardiac chest pain ^† 1	0/77 (0.00%)	0	1/76 (1.32%)	1
Hepatobiliary disorders
Cholecystitis ^† 1	1/77 (1.30%)	1	0/76 (0.00%)	0
Cholecystitis acute ^† 1	1/77 (1.30%)	1	1/76 (1.32%)	1
Cholelithiasis ^† 1	1/77 (1.30%)	1	0/76 (0.00%)	0
Hepatic failure ^† 1	0/77 (0.00%)	0	1/76 (1.32%)	1
Hepatotoxicity ^† 1	1/77 (1.30%)	1	0/76 (0.00%)	0
Infections and infestations
Abdominal abscess ^† 1	1/77 (1.30%)	1	0/76 (0.00%)	0
Arthritis bacterial ^† 1	1/77 (1.30%)	1	0/76 (0.00%)	0
Biliary sepsis ^† 1	0/77 (0.00%)	0	1/76 (1.32%)	1
Catheter site infection ^† 1	1/77 (1.30%)	1	0/76 (0.00%)	0
Clostridium difficile colitis ^† 1	2/77 (2.60%)	2	0/76 (0.00%)	0
Device related sepsis ^† 1	2/77 (2.60%)	2	0/76 (0.00%)	0
Escherichia urinary tract infection ^† 1	1/77 (1.30%)	1	0/76 (0.00%)	0
Neutropenic sepsis ^† 1	2/77 (2.60%)	2	0/76 (0.00%)	0
Peritonitis ^† 1	2/77 (2.60%)	2	0/76 (0.00%)	0
Pneumonia ^† 1	3/77 (3.90%)	3	1/76 (1.32%)	1
Pneumonia toxoplasmal ^† 1	1/77 (1.30%)	1	0/76 (0.00%)	0
Septic shock ^† 1	1/77 (1.30%)	1	1/76 (1.32%)	1
Wound infection ^† 1	1/77 (1.30%)	1	0/76 (0.00%)	0
Injury, poisoning and procedural complications
Fall ^† 1	1/77 (1.30%)	1	1/76 (1.32%)	1
Gastrointestinal stoma complication ^† 1	0/77 (0.00%)	0	1/76 (1.32%)	1
Postoperative wound complication ^† 1	1/77 (1.30%)	1	0/76 (0.00%)	0
Thoracic vertebral fracture ^† 1	0/77 (0.00%)	0	1/76 (1.32%)	1
Investigations
Blood bilirubin increased ^† 1	0/77 (0.00%)	0	2/76 (2.63%)	2
Blood calcium decreased ^† 1	0/77 (0.00%)	0	1/76 (1.32%)	1
Blood creatine phosphokinase increased ^† 1	0/77 (0.00%)	0	1/76 (1.32%)	1
Blood magnesium decreased ^† 1	0/77 (0.00%)	0	1/76 (1.32%)	1
Blood phosphorus decreased ^† 1	0/77 (0.00%)	0	1/76 (1.32%)	1
Blood potassium decreased ^† 1	0/77 (0.00%)	0	1/76 (1.32%)	1
Neutrophil count decreased ^† 1	0/77 (0.00%)	0	1/76 (1.32%)	1
Troponin T increased ^† 1	0/77 (0.00%)	0	1/76 (1.32%)	1
White blood cell count decreased ^† 1	0/77 (0.00%)	0	1/76 (1.32%)	1
Metabolism and nutrition disorders
Dehydration ^† 1	3/77 (3.90%)	3	5/76 (6.58%)	5
Fluid overload ^† 1	0/77 (0.00%)	0	1/76 (1.32%)	1
Hyperkalaemia ^† 1	1/77 (1.30%)	1	0/76 (0.00%)	0
Hyponatraemia ^† 1	0/77 (0.00%)	0	1/76 (1.32%)	1
Musculoskeletal and connective tissue disorders
Back pain ^† 1	0/77 (0.00%)	0	1/76 (1.32%)	1
Muscular weakness ^† 1	0/77 (0.00%)	0	1/76 (1.32%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cancer pain ^† 1	1/77 (1.30%)	1	0/76 (0.00%)	0
Malignant neoplasm progression ^† 1	8/77 (10.39%)	8	16/76 (21.05%)	16
Metastases to peritoneum ^† 1	0/77 (0.00%)	0	1/76 (1.32%)	1
Metastases to spine ^† 1	1/77 (1.30%)	1	0/76 (0.00%)	0
Skin cancer ^† 1	0/77 (0.00%)	0	1/76 (1.32%)	1
Nervous system disorders
Aphasia ^† 1	0/77 (0.00%)	0	1/76 (1.32%)	1
Cauda equina syndrome ^† 1	1/77 (1.30%)	1	0/76 (0.00%)	0
Ischaemic stroke ^† 1	1/77 (1.30%)	1	0/76 (0.00%)	0
Memory impairment ^† 1	0/77 (0.00%)	0	1/76 (1.32%)	1
Seizure ^† 1	0/77 (0.00%)	0	1/76 (1.32%)	1
Syncope ^† 1	1/77 (1.30%)	3	2/76 (2.63%)	2
Psychiatric disorders
Depressed mood ^† 1	0/77 (0.00%)	0	1/76 (1.32%)	1
Depression ^† 1	1/77 (1.30%)	1	0/76 (0.00%)	0
Renal and urinary disorders
Acute kidney injury ^† 1	2/77 (2.60%)	3	2/76 (2.63%)	2
Renal failure ^† 1	0/77 (0.00%)	0	1/76 (1.32%)	1
Reproductive system and breast disorders
Female genital tract fistula ^† 1	1/77 (1.30%)	1	0/76 (0.00%)	0
Respiratory, thoracic and mediastinal disorders
Acute respiratory distress syndrome ^† 1	1/77 (1.30%)	1	1/76 (1.32%)	1
Dyspnoea ^† 1	1/77 (1.30%)	1	0/76 (0.00%)	0
Dyspnoea exertional ^† 1	1/77 (1.30%)	1	0/76 (0.00%)	0
Hypoxia ^† 1	1/77 (1.30%)	1	0/76 (0.00%)	0
Pleural effusion ^† 1	0/77 (0.00%)	0	1/76 (1.32%)	1
Pneumonia aspiration ^† 1	0/77 (0.00%)	0	1/76 (1.32%)	1
Pulmonary congestion ^† 1	0/77 (0.00%)	0	1/76 (1.32%)	1
Pulmonary embolism ^† 1	3/77 (3.90%)	3	3/76 (3.95%)	4
Pulmonary oedema ^† 1	1/77 (1.30%)	1	1/76 (1.32%)	1
Skin and subcutaneous tissue disorders
Diabetic foot ^† 1	0/77 (0.00%)	0	1/76 (1.32%)	1
Palmar-plantar erythrodysaesthesia syndrome ^† 1	0/77 (0.00%)	0	1/76 (1.32%)	1
Rash erythematous ^† 1	0/77 (0.00%)	0	1/76 (1.32%)	1
Stevens-Johnson syndrome ^† 1	0/77 (0.00%)	0	1/76 (1.32%)	1
Vascular disorders
Deep vein thrombosis ^† 1	0/77 (0.00%)	0	4/76 (5.26%)	4
Hypertension ^† 1	3/77 (3.90%)	3	0/76 (0.00%)	0
Hypotension ^† 1	1/77 (1.30%)	2	2/76 (2.63%)	2
Thrombophlebitis superficial ^† 1	0/77 (0.00%)	0	1/76 (1.32%)	1
1 Term from vocabulary, MedDRA 21.0 † Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	0%
	Trifluridine/Tipiracil + Bevacizumab		Capecitabine + Bevacizumab
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	75/77 (97.40%)		69/76 (90.79%)
Blood and lymphatic system disorders
Anaemia ^† 1	22/77 (28.57%)	31	5/76 (6.58%)	7
Anaemia of chronic disease ^† 1	1/77 (1.30%)	1	1/76 (1.32%)	1
Anaemia of malignant disease ^† 1	5/77 (6.49%)	5	1/76 (1.32%)	2
Febrile neutropenia ^† 1	1/77 (1.30%)	1	0/76 (0.00%)	0
Haemolytic anaemia ^† 1	2/77 (2.60%)	2	0/76 (0.00%)	0
Leukopenia ^† 1	6/77 (7.79%)	9	2/76 (2.63%)	5
Neutropenia ^† 1	40/77 (51.95%)	181	5/76 (6.58%)	5
Spontaneous haematoma ^† 1	1/77 (1.30%)	1	1/76 (1.32%)	1
Thrombocytopenia ^† 1	11/77 (14.29%)	22	4/76 (5.26%)	5
Thrombocytosis ^† 1	4/77 (5.19%)	8	0/76 (0.00%)	0
Cardiac disorders
Angina pectoris ^† 1	1/77 (1.30%)	1	0/76 (0.00%)	0
Aortic valve thickening ^† 1	1/77 (1.30%)	1	0/76 (0.00%)	0
Arrhythmia ^† 1	0/77 (0.00%)	0	1/76 (1.32%)	1
Atrial fibrillation ^† 1	1/77 (1.30%)	1	0/76 (0.00%)	0
Bundle branch block right ^† 1	0/77 (0.00%)	0	1/76 (1.32%)	1
Supraventricular extrasystoles ^† 1	1/77 (1.30%)	1	0/76 (0.00%)	0
Tachycardia ^† 1	0/77 (0.00%)	0	1/76 (1.32%)	1
Ear and labyrinth disorders
Ear pain ^† 1	1/77 (1.30%)	1	1/76 (1.32%)	1
Vertigo ^† 1	2/77 (2.60%)	2	0/76 (0.00%)	0
Eye disorders
Dry eye ^† 1	1/77 (1.30%)	2	0/76 (0.00%)	0
Eye pain ^† 1	0/77 (0.00%)	0	1/76 (1.32%)	1
Eye pruritus ^† 1	0/77 (0.00%)	0	1/76 (1.32%)	1
Lacrimation increased ^† 1	0/77 (0.00%)	0	4/76 (5.26%)	5
Vision blurred ^† 1	1/77 (1.30%)	1	2/76 (2.63%)	2
Gastrointestinal disorders
Abdominal discomfort ^† 1	1/77 (1.30%)	1	0/76 (0.00%)	0
Abdominal pain ^† 1	9/77 (11.69%)	18	6/76 (7.89%)	7
Abdominal pain lower ^† 1	1/77 (1.30%)	1	0/76 (0.00%)	0
Abdominal pain upper ^† 1	2/77 (2.60%)	3	2/76 (2.63%)	3
Anal fissure ^† 1	0/77 (0.00%)	0	1/76 (1.32%)	1
Anal inflammation ^† 1	0/77 (0.00%)	0	1/76 (1.32%)	1
Aphthous ulcer ^† 1	2/77 (2.60%)	2	1/76 (1.32%)	1
Chronic gastritis ^† 1	1/77 (1.30%)	1	0/76 (0.00%)	0
Constipation ^† 1	13/77 (16.88%)	21	15/76 (19.74%)	17
Diarrhoea ^† 1	40/77 (51.95%)	91	31/76 (40.79%)	64
Dry mouth ^† 1	2/77 (2.60%)	2	6/76 (7.89%)	7
Dyschezia ^† 1	1/77 (1.30%)	1	0/76 (0.00%)	0
Dyspepsia ^† 1	6/77 (7.79%)	7	2/76 (2.63%)	2
Dysphagia ^† 1	1/77 (1.30%)	1	1/76 (1.32%)	1
Eructation ^† 1	2/77 (2.60%)	3	1/76 (1.32%)	1
Gastrointestinal motility disorder ^† 1	1/77 (1.30%)	1	0/76 (0.00%)	0
Gastrooesophageal reflux disease ^† 1	0/77 (0.00%)	0	2/76 (2.63%)	2
Gingival bleeding ^† 1	3/77 (3.90%)	4	1/76 (1.32%)	1
Haemorrhoids ^† 1	1/77 (1.30%)	1	0/76 (0.00%)	0
Lip dry ^† 1	0/77 (0.00%)	0	1/76 (1.32%)	1
Lip pain ^† 1	1/77 (1.30%)	1	0/76 (0.00%)	0
Lip swelling ^† 1	1/77 (1.30%)	1	0/76 (0.00%)	0
Mesenteric vein thrombosis ^† 1	0/77 (0.00%)	0	1/76 (1.32%)	1
Mouth ulceration ^† 1	2/77 (2.60%)	2	0/76 (0.00%)	0
Nausea ^† 1	36/77 (46.75%)	84	13/76 (17.11%)	23
Oral mucosa erosion ^† 1	1/77 (1.30%)	1	0/76 (0.00%)	0
Oral pain ^† 1	0/77 (0.00%)	0	1/76 (1.32%)	1
Pancreatitis chronic ^† 1	0/77 (0.00%)	0	1/76 (1.32%)	1
Periodontal disease ^† 1	1/77 (1.30%)	1	0/76 (0.00%)	0
Proctalgia ^† 1	3/77 (3.90%)	6	3/76 (3.95%)	3
Proctitis ^† 1	0/77 (0.00%)	0	1/76 (1.32%)	1
Rectal discharge ^† 1	1/77 (1.30%)	1	0/76 (0.00%)	0
Rectal haemorrhage ^† 1	0/77 (0.00%)	0	2/76 (2.63%)	2
Stomatitis ^† 1	13/77 (16.88%)	18	16/76 (21.05%)	29
Stomatitis haemorrhagic ^† 1	0/77 (0.00%)	0	1/76 (1.32%)	1
Toothache ^† 1	1/77 (1.30%)	1	0/76 (0.00%)	0
Vomiting ^† 1	22/77 (28.57%)	44	8/76 (10.53%)	8
General disorders
Asthenia ^† 1	14/77 (18.18%)	19	17/76 (22.37%)	22
Chest discomfort ^† 1	1/77 (1.30%)	1	0/76 (0.00%)	0
Chills ^† 1	1/77 (1.30%)	1	3/76 (3.95%)	3
Discomfort ^† 1	1/77 (1.30%)	1	0/76 (0.00%)	0
Early satiety ^† 1	1/77 (1.30%)	1	0/76 (0.00%)	0
Fatigue ^† 1	28/77 (36.36%)	45	23/76 (30.26%)	35
Feeling hot ^† 1	1/77 (1.30%)	1	0/76 (0.00%)	0
Impaired healing ^† 1	1/77 (1.30%)	1	0/76 (0.00%)	0
Influenza like illness ^† 1	3/77 (3.90%)	3	3/76 (3.95%)	3
Injection site haematoma ^† 1	0/77 (0.00%)	0	1/76 (1.32%)	1
Local swelling ^† 1	0/77 (0.00%)	0	1/76 (1.32%)	1
Malaise ^† 1	1/77 (1.30%)	2	0/76 (0.00%)	0
Mucosal inflammation ^† 1	0/77 (0.00%)	0	1/76 (1.32%)	1
Non-cardiac chest pain ^† 1	0/77 (0.00%)	0	1/76 (1.32%)	1
Oedema peripheral ^† 1	3/77 (3.90%)	4	3/76 (3.95%)	3
Pain ^† 1	0/77 (0.00%)	0	1/76 (1.32%)	1
Puncture site pain ^† 1	1/77 (1.30%)	1	0/76 (0.00%)	0
Pyrexia ^† 1	5/77 (6.49%)	5	4/76 (5.26%)	5
Tenderness ^† 1	0/77 (0.00%)	0	1/76 (1.32%)	1
Xerosis ^† 1	0/77 (0.00%)	0	1/76 (1.32%)	1
Hepatobiliary disorders
Cholecystitis chronic ^† 1	0/77 (0.00%)	0	1/76 (1.32%)	1
Hepatomegaly ^† 1	0/77 (0.00%)	0	1/76 (1.32%)	1
Hyperbilirubinaemia ^† 1	1/77 (1.30%)	1	5/76 (6.58%)	7
Infections and infestations
Bronchitis ^† 1	1/77 (1.30%)	1	0/76 (0.00%)	0
Conjunctivitis ^† 1	1/77 (1.30%)	2	3/76 (3.95%)	3
Cystitis ^† 1	0/77 (0.00%)	0	2/76 (2.63%)	2
Escherichia urinary tract infection ^† 1	1/77 (1.30%)	1	0/76 (0.00%)	0
Folliculitis ^† 1	0/77 (0.00%)	0	1/76 (1.32%)	1
Furuncle ^† 1	1/77 (1.30%)	1	0/76 (0.00%)	0
Gastroenteritis ^† 1	2/77 (2.60%)	2	0/76 (0.00%)	0
Gastrointestinal viral infection ^† 1	1/77 (1.30%)	1	0/76 (0.00%)	0
Gingivitis ^† 1	1/77 (1.30%)	1	0/76 (0.00%)	0
Hepatic cyst infection ^† 1	0/77 (0.00%)	0	1/76 (1.32%)	1
Influenza ^† 1	1/77 (1.30%)	1	1/76 (1.32%)	1
Labyrinthitis ^† 1	1/77 (1.30%)	1	0/76 (0.00%)	0
Lower respiratory tract infection bacterial ^† 1	0/77 (0.00%)	0	1/76 (1.32%)	1
Lung infection ^† 1	1/77 (1.30%)	2	1/76 (1.32%)	1
Oral candidiasis ^† 1	1/77 (1.30%)	1	3/76 (3.95%)	4
Oral fungal infection ^† 1	1/77 (1.30%)	1	0/76 (0.00%)	0
Oral herpes ^† 1	1/77 (1.30%)	1	4/76 (5.26%)	4
Oral infection ^† 1	1/77 (1.30%)	1	0/76 (0.00%)	0
Periumbilical abscess ^† 1	0/77 (0.00%)	0	1/76 (1.32%)	1
Pneumonia ^† 1	0/77 (0.00%)	0	1/76 (1.32%)	1
Pneumonia bacterial ^† 1	1/77 (1.30%)	1	1/76 (1.32%)	1
Rhinitis ^† 1	4/77 (5.19%)	4	1/76 (1.32%)	1
Skin candida ^† 1	0/77 (0.00%)	0	1/76 (1.32%)	1
Tooth abscess ^† 1	0/77 (0.00%)	0	1/76 (1.32%)	1
Upper respiratory tract infection ^† 1	7/77 (9.09%)	8	2/76 (2.63%)	2
Urinary tract infection ^† 1	7/77 (9.09%)	8	5/76 (6.58%)	6
Urinary tract infection bacterial ^† 1	1/77 (1.30%)	1	2/76 (2.63%)	3
Viral upper respiratory tract infection ^† 1	8/77 (10.39%)	9	5/76 (6.58%)	5
Vulvovaginal candidiasis ^† 1	1/77 (1.30%)	1	0/76 (0.00%)	0
Injury, poisoning and procedural complications
Abdominal wall wound ^† 1	1/77 (1.30%)	1	0/76 (0.00%)	0
Accidental overdose ^† 1	0/77 (0.00%)	0	2/76 (2.63%)	5
Clavicle fracture ^† 1	1/77 (1.30%)	1	0/76 (0.00%)	0
Contusion ^† 1	1/77 (1.30%)	1	0/76 (0.00%)	0
Fall ^† 1	5/77 (6.49%)	5	4/76 (5.26%)	6
Hand fracture ^† 1	0/77 (0.00%)	0	1/76 (1.32%)	1
Infusion related reaction ^† 1	1/77 (1.30%)	1	0/76 (0.00%)	0
Muscle strain ^† 1	1/77 (1.30%)	1	0/76 (0.00%)	0
Procedural pain ^† 1	1/77 (1.30%)	1	0/76 (0.00%)	0
Skin wound ^† 1	0/77 (0.00%)	0	1/76 (1.32%)	1
Stoma site haemorrhage ^† 1	1/77 (1.30%)	1	1/76 (1.32%)	1
Stoma site irritation ^† 1	1/77 (1.30%)	1	0/76 (0.00%)	0
Stoma site pain ^† 1	2/77 (2.60%)	2	0/76 (0.00%)	0
Traumatic haematoma ^† 1	1/77 (1.30%)	1	1/76 (1.32%)	1
Wound ^† 1	0/77 (0.00%)	0	2/76 (2.63%)	2
Wound complication ^† 1	1/77 (1.30%)	1	0/76 (0.00%)	0
Investigations
Activated partial thromboplastin time prolonged ^† 1	1/77 (1.30%)	1	1/76 (1.32%)	1
Alanine aminotransferase increased ^† 1	9/77 (11.69%)	11	2/76 (2.63%)	2
Aspartate aminotransferase increased ^† 1	7/77 (9.09%)	8	2/76 (2.63%)	2
Bilirubin conjugated increased ^† 1	1/77 (1.30%)	2	1/76 (1.32%)	1
Blood albumin decreased ^† 1	1/77 (1.30%)	1	0/76 (0.00%)	0
Blood alkaline phosphatase increased ^† 1	3/77 (3.90%)	3	2/76 (2.63%)	2
Blood bilirubin increased ^† 1	6/77 (7.79%)	18	8/76 (10.53%)	13
Blood bilirubin unconjugated increased ^† 1	0/77 (0.00%)	0	1/76 (1.32%)	1
Blood cholesterol increased ^† 1	1/77 (1.30%)	1	0/76 (0.00%)	0
Blood creatinine increased ^† 1	3/77 (3.90%)	5	1/76 (1.32%)	1
Blood glucose increased ^† 1	1/77 (1.30%)	1	0/76 (0.00%)	0
Blood lactate dehydrogenase decreased ^† 1	1/77 (1.30%)	1	0/76 (0.00%)	0
Blood lactate dehydrogenase increased ^† 1	1/77 (1.30%)	5	4/76 (5.26%)	5
Blood phosphorus increased ^† 1	1/77 (1.30%)	1	0/76 (0.00%)	0
Blood potassium decreased ^† 1	0/77 (0.00%)	0	1/76 (1.32%)	1
Blood potassium increased ^† 1	0/77 (0.00%)	0	1/76 (1.32%)	1
Blood pressure increased ^† 1	2/77 (2.60%)	3	0/76 (0.00%)	0
Blood urea increased ^† 1	0/77 (0.00%)	0	1/76 (1.32%)	1
Blood urine present ^† 1	0/77 (0.00%)	0	1/76 (1.32%)	1
Carcinoembryonic antigen increased ^† 1	0/77 (0.00%)	0	1/76 (1.32%)	1
Creatinine renal clearance decreased ^† 1	1/77 (1.30%)	1	1/76 (1.32%)	1
Eosinophil count decreased ^† 1	2/77 (2.60%)	2	0/76 (0.00%)	0
Gamma-glutamyltransferase increased ^† 1	6/77 (7.79%)	6	2/76 (2.63%)	3
Glomerular filtration rate decreased ^† 1	1/77 (1.30%)	1	0/76 (0.00%)	0
Heart rate irregular ^† 1	0/77 (0.00%)	0	1/76 (1.32%)	1
International normalised ratio increased ^† 1	1/77 (1.30%)	1	2/76 (2.63%)	2
Lymphocyte count decreased ^† 1	4/77 (5.19%)	7	1/76 (1.32%)	2
Monocyte count decreased ^† 1	2/77 (2.60%)	2	0/76 (0.00%)	0
Neutrophil count decreased ^† 1	18/77 (23.38%)	90	1/76 (1.32%)	1
Neutrophil count increased ^† 1	1/77 (1.30%)	1	0/76 (0.00%)	0
Platelet count decreased ^† 1	7/77 (9.09%)	22	3/76 (3.95%)	5
Platelet count increased ^† 1	2/77 (2.60%)	3	0/76 (0.00%)	0
Weight decreased ^† 1	9/77 (11.69%)	12	6/76 (7.89%)	7
Weight increased ^† 1	0/77 (0.00%)	0	1/76 (1.32%)	1
White blood cell count decreased ^† 1	15/77 (19.48%)	37	1/76 (1.32%)	1
White blood cell count increased ^† 1	1/77 (1.30%)	1	0/76 (0.00%)	0
Metabolism and nutrition disorders
Decreased appetite ^† 1	29/77 (37.66%)	46	15/76 (19.74%)	23
Gout ^† 1	1/77 (1.30%)	1	0/76 (0.00%)	0
Hypercalcaemia ^† 1	2/77 (2.60%)	2	0/76 (0.00%)	0
Hyperglycaemia ^† 1	3/77 (3.90%)	6	2/76 (2.63%)	2
Hyperkalaemia ^† 1	4/77 (5.19%)	5	0/76 (0.00%)	0
Hyperphosphataemia ^† 1	1/77 (1.30%)	1	0/76 (0.00%)	0
Hypertriglyceridaemia ^† 1	1/77 (1.30%)	1	0/76 (0.00%)	0
Hypoalbuminaemia ^† 1	4/77 (5.19%)	4	2/76 (2.63%)	2
Hypocalcaemia ^† 1	2/77 (2.60%)	4	1/76 (1.32%)	1
Hypochloraemia ^† 1	1/77 (1.30%)	1	0/76 (0.00%)	0
Hypoglycaemia ^† 1	1/77 (1.30%)	1	0/76 (0.00%)	0
Hypokalaemia ^† 1	0/77 (0.00%)	0	1/76 (1.32%)	1
Hypomagnesaemia ^† 1	3/77 (3.90%)	3	1/76 (1.32%)	1
Hyponatraemia ^† 1	3/77 (3.90%)	3	0/76 (0.00%)	0
Hypophosphataemia ^† 1	1/77 (1.30%)	1	1/76 (1.32%)	1
Metabolic acidosis ^† 1	1/77 (1.30%)	1	0/76 (0.00%)	0
Musculoskeletal and connective tissue disorders
Arthralgia ^† 1	6/77 (7.79%)	8	3/76 (3.95%)	3
Back pain ^† 1	6/77 (7.79%)	6	7/76 (9.21%)	7
Bursitis ^† 1	1/77 (1.30%)	1	0/76 (0.00%)	0
Coccydynia ^† 1	0/77 (0.00%)	0	1/76 (1.32%)	1
Intervertebral disc compression ^† 1	0/77 (0.00%)	0	1/76 (1.32%)	1
Joint swelling ^† 1	1/77 (1.30%)	1	0/76 (0.00%)	0
Mobility decreased ^† 1	1/77 (1.30%)	1	0/76 (0.00%)	0
Muscle spasms ^† 1	0/77 (0.00%)	0	1/76 (1.32%)	1
Muscular weakness ^† 1	1/77 (1.30%)	1	0/76 (0.00%)	0
Musculoskeletal chest pain ^† 1	1/77 (1.30%)	1	1/76 (1.32%)	1
Musculoskeletal pain ^† 1	2/77 (2.60%)	2	1/76 (1.32%)	1
Myalgia ^† 1	1/77 (1.30%)	2	4/76 (5.26%)	5
Neck pain ^† 1	2/77 (2.60%)	2	1/76 (1.32%)	1
Osteoarthritis ^† 1	1/77 (1.30%)	1	0/76 (0.00%)	0
Pain in extremity ^† 1	4/77 (5.19%)	4	1/76 (1.32%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cancer pain ^† 1	0/77 (0.00%)	0	1/76 (1.32%)	1
Malignant neoplasm progression ^† 1	9/77 (11.69%)	9	3/76 (3.95%)	3
Nervous system disorders
Amnesia ^† 1	0/77 (0.00%)	0	1/76 (1.32%)	1
Aphonia ^† 1	0/77 (0.00%)	0	2/76 (2.63%)	2
Balance disorder ^† 1	0/77 (0.00%)	0	1/76 (1.32%)	1
Dizziness ^† 1	5/77 (6.49%)	7	8/76 (10.53%)	10
Dizziness exertional ^† 1	1/77 (1.30%)	1	1/76 (1.32%)	1
Dizziness postural ^† 1	1/77 (1.30%)	1	1/76 (1.32%)	1
Dysarthria ^† 1	0/77 (0.00%)	0	1/76 (1.32%)	1
Dysgeusia ^† 1	7/77 (9.09%)	8	8/76 (10.53%)	8
Essential tremor ^† 1	1/77 (1.30%)	1	0/76 (0.00%)	0
Headache ^† 1	7/77 (9.09%)	13	4/76 (5.26%)	4
Hyperaesthesia ^† 1	0/77 (0.00%)	0	1/76 (1.32%)	1
Hypoaesthesia ^† 1	0/77 (0.00%)	0	1/76 (1.32%)	2
Memory impairment ^† 1	1/77 (1.30%)	1	1/76 (1.32%)	1
Neuralgia ^† 1	1/77 (1.30%)	2	0/76 (0.00%)	0
Neuropathy peripheral ^† 1	0/77 (0.00%)	0	3/76 (3.95%)	3
Neurotoxicity ^† 1	0/77 (0.00%)	0	1/76 (1.32%)	1
Orthostatic intolerance ^† 1	0/77 (0.00%)	0	1/76 (1.32%)	1
Paraesthesia ^† 1	1/77 (1.30%)	1	2/76 (2.63%)	2
Peripheral sensory neuropathy ^† 1	2/77 (2.60%)	2	1/76 (1.32%)	1
Presyncope ^† 1	1/77 (1.30%)	1	2/76 (2.63%)	3
Restless legs syndrome ^† 1	1/77 (1.30%)	1	1/76 (1.32%)	1
Sciatica ^† 1	1/77 (1.30%)	1	0/76 (0.00%)	0
Somnolence ^† 1	0/77 (0.00%)	0	1/76 (1.32%)	1
Tremor ^† 1	1/77 (1.30%)	1	0/76 (0.00%)	0
Psychiatric disorders
Anxiety ^† 1	0/77 (0.00%)	0	2/76 (2.63%)	2
Confusional state ^† 1	1/77 (1.30%)	1	1/76 (1.32%)	2
Depression ^† 1	1/77 (1.30%)	1	0/76 (0.00%)	0
Disorientation ^† 1	0/77 (0.00%)	0	1/76 (1.32%)	1
Insomnia ^† 1	6/77 (7.79%)	6	1/76 (1.32%)	1
Mood altered ^† 1	1/77 (1.30%)	1	0/76 (0.00%)	0
Restlessness ^† 1	1/77 (1.30%)	1	0/76 (0.00%)	0
Stress ^† 1	1/77 (1.30%)	1	0/76 (0.00%)	0
Renal and urinary disorders
Anuria ^† 1	1/77 (1.30%)	1	0/76 (0.00%)	0
Dysuria ^† 1	0/77 (0.00%)	0	3/76 (3.95%)	3
Glycosuria ^† 1	0/77 (0.00%)	0	1/76 (1.32%)	2
Haematuria ^† 1	1/77 (1.30%)	1	2/76 (2.63%)	2
Lower urinary tract symptoms ^† 1	1/77 (1.30%)	1	0/76 (0.00%)	0
Micturition urgency ^† 1	0/77 (0.00%)	0	1/76 (1.32%)	1
Nocturia ^† 1	0/77 (0.00%)	0	1/76 (1.32%)	1
Pollakiuria ^† 1	0/77 (0.00%)	0	1/76 (1.32%)	1
Proteinuria ^† 1	5/77 (6.49%)	6	4/76 (5.26%)	5
Urinary incontinence ^† 1	0/77 (0.00%)	0	1/76 (1.32%)	1
Urinary retention ^† 1	0/77 (0.00%)	0	1/76 (1.32%)	1
Reproductive system and breast disorders
Benign prostatic hyperplasia ^† 1	0/77 (0.00%)	0	1/76 (1.32%)	1
Oedema genital ^† 1	1/77 (1.30%)	1	0/76 (0.00%)	0
Prostatitis ^† 1	0/77 (0.00%)	0	1/76 (1.32%)	1
Respiratory, thoracic and mediastinal disorders
Catarrh ^† 1	1/77 (1.30%)	1	0/76 (0.00%)	0
Chronic obstructive pulmonary disease ^† 1	0/77 (0.00%)	0	1/76 (1.32%)	1
Cough ^† 1	2/77 (2.60%)	2	6/76 (7.89%)	6
Dysphonia ^† 1	4/77 (5.19%)	5	1/76 (1.32%)	1
Dyspnoea ^† 1	5/77 (6.49%)	5	8/76 (10.53%)	11
Dyspnoea exertional ^† 1	2/77 (2.60%)	2	2/76 (2.63%)	2
Epistaxis ^† 1	4/77 (5.19%)	6	4/76 (5.26%)	6
Hiccups ^† 1	1/77 (1.30%)	1	1/76 (1.32%)	1
Nasal congestion ^† 1	1/77 (1.30%)	1	0/76 (0.00%)	0
Nasal dryness ^† 1	1/77 (1.30%)	1	0/76 (0.00%)	0
Nasal inflammation ^† 1	1/77 (1.30%)	1	0/76 (0.00%)	0
Oropharyngeal pain ^† 1	1/77 (1.30%)	1	1/76 (1.32%)	1
Pneumonia aspiration ^† 1	0/77 (0.00%)	0	1/76 (1.32%)	1
Productive cough ^† 1	1/77 (1.30%)	1	3/76 (3.95%)	3
Pulmonary mass ^† 1	0/77 (0.00%)	0	1/76 (1.32%)	1
Pulmonary pain ^† 1	0/77 (0.00%)	0	1/76 (1.32%)	1
Rhinalgia ^† 1	1/77 (1.30%)	1	0/76 (0.00%)	0
Rhinorrhoea ^† 1	0/77 (0.00%)	0	3/76 (3.95%)	3
Sneezing ^† 1	1/77 (1.30%)	1	0/76 (0.00%)	0
Skin and subcutaneous tissue disorders
Alopecia ^† 1	17/77 (22.08%)	17	0/76 (0.00%)	0
Drug eruption ^† 1	0/77 (0.00%)	0	1/76 (1.32%)	1
Dry skin ^† 1	4/77 (5.19%)	4	4/76 (5.26%)	4
Erythema ^† 1	0/77 (0.00%)	0	2/76 (2.63%)	2
Hyperhidrosis ^† 1	0/77 (0.00%)	0	2/76 (2.63%)	2
Nail discolouration ^† 1	0/77 (0.00%)	0	1/76 (1.32%)	1
Nail disorder ^† 1	0/77 (0.00%)	0	1/76 (1.32%)	1
Night sweats ^† 1	1/77 (1.30%)	1	0/76 (0.00%)	0
Onychalgia ^† 1	0/77 (0.00%)	0	1/76 (1.32%)	1
Onychomadesis ^† 1	0/77 (0.00%)	0	1/76 (1.32%)	1
Palmar-plantar erythrodysaesthesia syndrome ^† 1	3/77 (3.90%)	4	39/76 (51.32%)	49
Pruritus ^† 1	2/77 (2.60%)	3	1/76 (1.32%)	1
Rash ^† 1	1/77 (1.30%)	1	1/76 (1.32%)	1
Rash erythematous ^† 1	0/77 (0.00%)	0	2/76 (2.63%)	2
Skin discolouration ^† 1	0/77 (0.00%)	0	1/76 (1.32%)	2
Skin fissures ^† 1	1/77 (1.30%)	1	0/76 (0.00%)	0
Skin hyperpigmentation ^† 1	0/77 (0.00%)	0	2/76 (2.63%)	2
Vascular disorders
Deep vein thrombosis ^† 1	0/77 (0.00%)	0	1/76 (1.32%)	1
Hot flush ^† 1	0/77 (0.00%)	0	1/76 (1.32%)	1
Hypertension ^† 1	9/77 (11.69%)	10	10/76 (13.16%)	12
Hypotension ^† 1	4/77 (5.19%)	5	1/76 (1.32%)	1
1 Term from vocabulary, MedDRA 21.0 † Indicates events were collected by systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

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Name/Title:	Dr Patrick Therasse
Organization:	Institut de Recherches Internationales Servier (I.R.I.S.)
Phone:	+33 1 55 72 43 47
EMail:	patrick.therasse@servier.com

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Van Cutsem E, Danielewicz I, Saunders MP, Pfeiffer P, Argiles G, Borg C, Glynne-Jones R, Punt CJA, Van de Wouw AJ, Fedyanin M, Stroyakovskiy D, Kroening H, Garcia-Alfonso P, Wasan H, Falcone A, Fougeray R, Egorov A, Amellal N, Moiseyenko V. First-line trifluridine/tipiracil + bevacizumab in patients with unresectable metastatic colorectal cancer: final survival analysis in the TASCO1 study. Br J Cancer. 2022 Jun;126(11):1548-1554. doi: 10.1038/s41416-022-01737-2. Epub 2022 Apr 19.

Van Cutsem E, Danielewicz I, Saunders MP, Pfeiffer P, Argiles G, Borg C, Glynne-Jones R, Punt CJA, Van de Wouw AJ, Fedyanin M, Stroyakovskiy D, Kroening H, Garcia-Alfonso P, Wasan H, Falcone A, Kanehisa A, Egorov A, Aubel P, Amellal N, Moiseenko V. Trifluridine/tipiracil plus bevacizumab in patients with untreated metastatic colorectal cancer ineligible for intensive therapy: the randomized TASCO1 study. Ann Oncol. 2020 Sep;31(9):1160-1168. doi: 10.1016/j.annonc.2020.05.024. Epub 2020 Jun 1.

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Responsible Party:	Servier ( Institut de Recherches Internationales Servier )
ClinicalTrials.gov Identifier:	NCT02743221
Other Study ID Numbers:	CL2-95005-002 2015-004544-18 ( EudraCT Number )
First Submitted:	February 24, 2016
First Posted:	April 19, 2016
Results First Submitted:	January 15, 2019
Results First Posted:	April 16, 2019
Last Update Posted:	October 5, 2021

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