Trial Outcomes & Findings for Diffuse Gastric and Esophagogastric Junction Cancer S-1 Trial (NCT NCT01285557)

Last Updated: 2024-09-19

Results Overview

OS was defined as the time from randomization to the date of death for the ITT population. Participants who did not die were censored at the date last known to be alive. Analysis was performed by using Kaplan-Meier method.

Recruitment status

TERMINATED

Study phase

PHASE3

Target enrollment

361 participants

Primary outcome timeframe

From the date of randomization until disease progression or death, cut-off date: 15 August 2014 (approximately 40 months)

Results posted on

2024-09-19

Participant Flow

A total of 690 participants were screened from 14 April 2011 to 25 February 2014, of which 361 participants enrolled in the study. The data cut-off date for all clinical data except overall survival was 07 Mar 2014 and for overall survival was 15 Aug 2014. The participants were randomized using interactive Voice/Web randomization system(2:1 ratio) to receive S-1/cisplatin or 5-Fluorouracil (5-FU)/cisplatin. A total of 329 participants failed screening due to failure to meet inclusion criteria.

Randomization was stratified by the histologic subtype (adenocarcinoma, diffuse type or signet ring cell adenocarcinoma); extent of metastasis (1 versus more than 1 metastatic site); Eastern Cooperative Oncology Group (ECOG) performance status (0 or 1) and region (North America, Western Europe, Eastern Europe, Rest of world). Cut-off dates for all clinical data collection was 07 March 2014 and for overall survival analysis was 15 August 2014.

Participant milestones

Participant milestones
Measure	S-1+Cisplatin Participants received S-1 25 milligrams per meter square (mg/m\^2) orally twice daily (BID) every 12 hours from Day 1 through Day 21, 1 hour before or after meal with a glass of water; followed by a 7-day rest period from Day 22 to Day 28 in a 28-day cycle. Participants received a single dose of cisplatin 75 mg/m\^2 as a 1- to 3-hour intravenous (IV) infusion on Day 1 following the morning dose of S-1 for a maximum of 8 cycles (each cycle of 28 days). Participants received study medication until progression of disease (PD), adverse event (AE), withdrawal of consent, or other reason for discontinuation, whichever happened earlier.	5FU+Cisplatin Participants received 5-FU 800 mg/m\^2 per 24 hours as continuous IV infusion over 120 hours from Day 1 through Day 5 followed by a 16-day rest period on Days 6 through 21 in a 21-day cycle. Participants received a single dose of cisplatin 80 mg/m\^2 as a 1- to 3-hour IV infusion on Day 1 prior to the start of the 5-FU infusion on Day 1 for a maximum of 8 cycles (each cycle of 21 days). Participants received study medication until PD, AE, withdrawal of consent, or other reason for discontinuation, whichever happened earlier.
Overall Study STARTED	239	122
Overall Study Treated	238	121
Overall Study As Treated (AT) Population	230	118
Overall Study COMPLETED	0	0
Overall Study NOT COMPLETED	239	122

Reasons for withdrawal

Reasons for withdrawal
Measure	S-1+Cisplatin Participants received S-1 25 milligrams per meter square (mg/m\^2) orally twice daily (BID) every 12 hours from Day 1 through Day 21, 1 hour before or after meal with a glass of water; followed by a 7-day rest period from Day 22 to Day 28 in a 28-day cycle. Participants received a single dose of cisplatin 75 mg/m\^2 as a 1- to 3-hour intravenous (IV) infusion on Day 1 following the morning dose of S-1 for a maximum of 8 cycles (each cycle of 28 days). Participants received study medication until progression of disease (PD), adverse event (AE), withdrawal of consent, or other reason for discontinuation, whichever happened earlier.	5FU+Cisplatin Participants received 5-FU 800 mg/m\^2 per 24 hours as continuous IV infusion over 120 hours from Day 1 through Day 5 followed by a 16-day rest period on Days 6 through 21 in a 21-day cycle. Participants received a single dose of cisplatin 80 mg/m\^2 as a 1- to 3-hour IV infusion on Day 1 prior to the start of the 5-FU infusion on Day 1 for a maximum of 8 cycles (each cycle of 21 days). Participants received study medication until PD, AE, withdrawal of consent, or other reason for discontinuation, whichever happened earlier.
Overall Study Death	173	90
Overall Study Lost to Follow-up	6	2
Overall Study Withdrew Consent	6	1
Overall Study Sponsor Study Termination	23	13
Overall Study Randomized but not treated	1	1
Overall Study Study follow-up ongoing	28	14
Overall Study Sponsor Decision	2	1

Baseline Characteristics

Diffuse Gastric and Esophagogastric Junction Cancer S-1 Trial

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	S-1+Cisplatin n=239 Participants Participants received S-1 25 mg/m\^2 orally BID every 12 hours from Day 1 through Day 21, 1 hour before or after meal with a glass of water; followed by a 7-day rest period from Day 22 to Day 28 in a 28-day cycle. Participants received a single dose of cisplatin 75 mg/m\^2 as a 1- to 3-hour IV infusion on Day 1 following the morning dose of S-1 for a maximum of 8 cycles (each cycle of 28 days). Participants received study medication until PD, AE, withdrawal of consent, or other reason for discontinuation, whichever happened earlier.	5FU+Cisplatin n=122 Participants Participants received 5-FU 800 mg/m\^2 per 24 hours as continuous IV infusion over 120 hours from Day 1 through Day 5 followed by a 16-day rest period on Days 6 through 21 in a 21-day cycle. Participants received a single dose of cisplatin 80 mg/m\^2 as a 1- to 3-hour IV infusion on Day 1 prior to the start of the 5-FU infusion on Day 1 for a maximum of 8 cycles (each cycle of 21 days). Participants received study medication until PD, AE, withdrawal of consent, or other reason for discontinuation, whichever happened earlier.	Total n=361 Participants Total of all reporting groups
Age, Continuous	55.1 years STANDARD_DEVIATION 11.01 • n=5 Participants	55.8 years STANDARD_DEVIATION 11.80 • n=7 Participants	55.4 years STANDARD_DEVIATION 11.27 • n=5 Participants
Sex: Female, Male Female	115 Participants n=5 Participants	62 Participants n=7 Participants	177 Participants n=5 Participants
Sex: Female, Male Male	124 Participants n=5 Participants	60 Participants n=7 Participants	184 Participants n=5 Participants
Race/Ethnicity, Customized Caucasian/White	226 Participants n=5 Participants	117 Participants n=7 Participants	343 Participants n=5 Participants
Race/Ethnicity, Customized Black	4 Participants n=5 Participants	2 Participants n=7 Participants	6 Participants n=5 Participants
Race/Ethnicity, Customized Asian/Oriental	4 Participants n=5 Participants	0 Participants n=7 Participants	4 Participants n=5 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race/Ethnicity, Customized Other	3 Participants n=5 Participants	3 Participants n=7 Participants	6 Participants n=5 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status ECOG Grade 0	75 Participants n=5 Participants	38 Participants n=7 Participants	113 Participants n=5 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status ECOG Grade 1	164 Participants n=5 Participants	83 Participants n=7 Participants	247 Participants n=5 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status Missing	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants

PRIMARY outcome

Timeframe: From the date of randomization until disease progression or death, cut-off date: 15 August 2014 (approximately 40 months)

Population: Analysis was performed on the ITT population that included all randomized participants.

Outcome measures

Outcome measures
Measure	S-1+Cisplatin n=239 Participants Participants received S-1 25 mg/m\^2 orally BID every 12 hours from Day 1 through Day 21, 1 hour before or after meal with a glass of water; followed by a 7-day rest period from Day 22 to Day 28 in a 28-day cycle. Participants received a single dose of cisplatin 75 mg/m\^2 as a 1- to 3-hour IV infusion on Day 1 following the morning dose of S-1 for a maximum of 8 cycles (each cycle of 28 days). Participants received study medication until PD, AE, withdrawal of consent, or other reason for discontinuation, whichever happened earlier.	5FU+Cisplatin n=122 Participants Participants received 5-FU 800 mg/m\^2 per 24 hours as continuous IV infusion over 120 hours from Day 1 through Day 5 followed by a 16-day rest period on Days 6 through 21 in a 21-day cycle. Participants received a single dose of cisplatin 80 mg/m\^2 as a 1- to 3-hour IV infusion on Day 1 prior to the start of the 5-FU infusion on Day 1 for a maximum of 8 cycles (each cycle of 21 days). Participants received study medication until PD, AE, withdrawal of consent, or other reason for discontinuation, whichever happened earlier.
Overall Survival (OS)	7.5 months Interval 6.7 to 9.3	6.6 months Interval 5.7 to 8.1

SECONDARY outcome

Timeframe: From date of randomization until disease progression or death, cut-off date: 07 March 2014 (approximately 34.7 months)

Population: Analysis was performed on the ITT population.

PFS was defined as the time from date of randomization until date of radiological disease progression or death due to any cause. Disease Progression was defined according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, where any of the 3 criteria have been met: 1) at least 20% increase in the sum of diameters of the target lesions, taking as reference the smallest sum on study, including the baseline sum, 2) Progression in no-target lesion(s), 3) appearance of new lesion(s) Participants who were alive with no PD were censored at the date of the last tumor assessment. Participants who received new anticancer therapy before disease progression were censored at the date of the last evaluable tumor assessment before new anticancer therapy was initiated. Analysis was performed by using Kaplan-Meier method.

Outcome measures

Outcome measures
Measure	S-1+Cisplatin n=239 Participants Participants received S-1 25 mg/m\^2 orally BID every 12 hours from Day 1 through Day 21, 1 hour before or after meal with a glass of water; followed by a 7-day rest period from Day 22 to Day 28 in a 28-day cycle. Participants received a single dose of cisplatin 75 mg/m\^2 as a 1- to 3-hour IV infusion on Day 1 following the morning dose of S-1 for a maximum of 8 cycles (each cycle of 28 days). Participants received study medication until PD, AE, withdrawal of consent, or other reason for discontinuation, whichever happened earlier.	5FU+Cisplatin n=122 Participants Participants received 5-FU 800 mg/m\^2 per 24 hours as continuous IV infusion over 120 hours from Day 1 through Day 5 followed by a 16-day rest period on Days 6 through 21 in a 21-day cycle. Participants received a single dose of cisplatin 80 mg/m\^2 as a 1- to 3-hour IV infusion on Day 1 prior to the start of the 5-FU infusion on Day 1 for a maximum of 8 cycles (each cycle of 21 days). Participants received study medication until PD, AE, withdrawal of consent, or other reason for discontinuation, whichever happened earlier.
Progression-free Survival (PFS)	4.4 months Interval 3.8 to 5.6	3.9 months Interval 3.6 to 5.2

SECONDARY outcome

Timeframe: From date of randomization until disease progression, cut-off date: 07 March 2014 (approximately 34.7 months)

Population: Analysis was performed on the ITT population.

TTF was defined as the time from date of randomization until date of PD (clinical or radiologic), or permanent discontinuation of study treatment (S-1 or 5-FU), or death due to any cause. Participates who were still on study treatment at the time of the analysis were censored at the last date the participants was known to be on treatment.

Outcome measures

Outcome measures
Measure	S-1+Cisplatin n=239 Participants Participants received S-1 25 mg/m\^2 orally BID every 12 hours from Day 1 through Day 21, 1 hour before or after meal with a glass of water; followed by a 7-day rest period from Day 22 to Day 28 in a 28-day cycle. Participants received a single dose of cisplatin 75 mg/m\^2 as a 1- to 3-hour IV infusion on Day 1 following the morning dose of S-1 for a maximum of 8 cycles (each cycle of 28 days). Participants received study medication until PD, AE, withdrawal of consent, or other reason for discontinuation, whichever happened earlier.	5FU+Cisplatin n=122 Participants Participants received 5-FU 800 mg/m\^2 per 24 hours as continuous IV infusion over 120 hours from Day 1 through Day 5 followed by a 16-day rest period on Days 6 through 21 in a 21-day cycle. Participants received a single dose of cisplatin 80 mg/m\^2 as a 1- to 3-hour IV infusion on Day 1 prior to the start of the 5-FU infusion on Day 1 for a maximum of 8 cycles (each cycle of 21 days). Participants received study medication until PD, AE, withdrawal of consent, or other reason for discontinuation, whichever happened earlier.
Time to Treatment Failure (TTF)	4.2 months Interval 3.8 to 4.9	3.8 months Interval 3.4 to 4.3

SECONDARY outcome

Timeframe: From first dose of study medication up to 30 days of last study medication (maximum duration: 35.7 months)

Population: Analysis was performed on the as treated (AT) population that included all participants who initiated treatment with either of the 2 regimens with treatment assignment designated according to actual treatment received.

AE was defined as any untoward medical condition that occurs in a participants while participating in a clinical study and does not necessarily had to have a causal relationship with the use of the study medication. A serious adverse event (SAE) was defined as any untoward medical occurrence that resulted in any of the following outcomes: death, life-threatening, required initial or prolonged in-patient hospitalization, persistent or significant disability/incapacity, congenital anomaly/birth defect, or considered as medically important event. TEAEs were defined as AEs that developed or worsened or became serious during on-treatment period (from first dose of study medication up to 30 days of last study medication \[maximum duration: 35.7 months\]).

Outcome measures

Outcome measures
Measure	S-1+Cisplatin n=230 Participants Participants received S-1 25 mg/m\^2 orally BID every 12 hours from Day 1 through Day 21, 1 hour before or after meal with a glass of water; followed by a 7-day rest period from Day 22 to Day 28 in a 28-day cycle. Participants received a single dose of cisplatin 75 mg/m\^2 as a 1- to 3-hour IV infusion on Day 1 following the morning dose of S-1 for a maximum of 8 cycles (each cycle of 28 days). Participants received study medication until PD, AE, withdrawal of consent, or other reason for discontinuation, whichever happened earlier.	5FU+Cisplatin n=118 Participants Participants received 5-FU 800 mg/m\^2 per 24 hours as continuous IV infusion over 120 hours from Day 1 through Day 5 followed by a 16-day rest period on Days 6 through 21 in a 21-day cycle. Participants received a single dose of cisplatin 80 mg/m\^2 as a 1- to 3-hour IV infusion on Day 1 prior to the start of the 5-FU infusion on Day 1 for a maximum of 8 cycles (each cycle of 21 days). Participants received study medication until PD, AE, withdrawal of consent, or other reason for discontinuation, whichever happened earlier.
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAE) TEAE	214 Participants	111 Participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAE) TESAE	63 Participants	31 Participants

SECONDARY outcome

Timeframe: From first dose of study medication up to 30 days of last study medication (maximum duration: 35.7 months)

Population: Analysis was performed on the as treated (AT) population.

An AE was any untoward medical condition that occurred in a participants while participating in a clinical study and does not necessarily had to have a causal relationship with the use of the study medication. TEAEs were defined as AEs that developed or worsened or became serious during on-treatment period (from first dose of study medication up to 30 days of last study medication \[maximum duration: 35.7 months\]).

Outcome measures

Outcome measures
Measure	S-1+Cisplatin n=230 Participants Participants received S-1 25 mg/m\^2 orally BID every 12 hours from Day 1 through Day 21, 1 hour before or after meal with a glass of water; followed by a 7-day rest period from Day 22 to Day 28 in a 28-day cycle. Participants received a single dose of cisplatin 75 mg/m\^2 as a 1- to 3-hour IV infusion on Day 1 following the morning dose of S-1 for a maximum of 8 cycles (each cycle of 28 days). Participants received study medication until PD, AE, withdrawal of consent, or other reason for discontinuation, whichever happened earlier.	5FU+Cisplatin n=118 Participants Participants received 5-FU 800 mg/m\^2 per 24 hours as continuous IV infusion over 120 hours from Day 1 through Day 5 followed by a 16-day rest period on Days 6 through 21 in a 21-day cycle. Participants received a single dose of cisplatin 80 mg/m\^2 as a 1- to 3-hour IV infusion on Day 1 prior to the start of the 5-FU infusion on Day 1 for a maximum of 8 cycles (each cycle of 21 days). Participants received study medication until PD, AE, withdrawal of consent, or other reason for discontinuation, whichever happened earlier.
Number of Participants With TEAEs With Severity Greater Than or Equal to (>=) Grade 3	157 Participants	78 Participants

SECONDARY outcome

Timeframe: From date of first study medication until cut-off date: 07 March 2014 (approximately 34.7 months)

Population: Analysis was performed on the ITT population. Here, 'overall number of participants analyzed' signifies participants with available data for the outcome measure.

ORR was defined as the percentage of participants with objective evidence of complete response (CR) or partial response (PR) based on the Investigator review of the images and application of Response Evaluation Criteria in Solid Tumors (RECIST) criteria. CR was defined as the disappearance of all target or non-target lesions. Any pathological lymph nodes for target lesions or all lymph nodes for non-target lesions were non-pathological morphologically that was reduced in size in short axis to less than (\<) 10 millimeter (mm). PR was defined as target lesions with at least 30% decrease in the sum of diameters, taking baseline sum diameters as reference.

Outcome measures

Outcome measures
Measure	S-1+Cisplatin n=193 Participants Participants received S-1 25 mg/m\^2 orally BID every 12 hours from Day 1 through Day 21, 1 hour before or after meal with a glass of water; followed by a 7-day rest period from Day 22 to Day 28 in a 28-day cycle. Participants received a single dose of cisplatin 75 mg/m\^2 as a 1- to 3-hour IV infusion on Day 1 following the morning dose of S-1 for a maximum of 8 cycles (each cycle of 28 days). Participants received study medication until PD, AE, withdrawal of consent, or other reason for discontinuation, whichever happened earlier.	5FU+Cisplatin n=91 Participants Participants received 5-FU 800 mg/m\^2 per 24 hours as continuous IV infusion over 120 hours from Day 1 through Day 5 followed by a 16-day rest period on Days 6 through 21 in a 21-day cycle. Participants received a single dose of cisplatin 80 mg/m\^2 as a 1- to 3-hour IV infusion on Day 1 prior to the start of the 5-FU infusion on Day 1 for a maximum of 8 cycles (each cycle of 21 days). Participants received study medication until PD, AE, withdrawal of consent, or other reason for discontinuation, whichever happened earlier.
Overall Response Rate (ORR): Percentage of Participants With Overall Response	34.7 percentage of participants Interval 28.0 to 41.9	19.8 percentage of participants Interval 12.2 to 29.4

SECONDARY outcome

Timeframe: From date of first study medication until cut-off date: 07 March 2014 (approximately 34.7 months)

Population: Analysis was performed on the ITT population. Here, 'overall number of participants analyzed' signifies participants with available data for the outcome measure.

Duration of response was defined as the time (in months) from date of first confirmed response (CR or PR) to date of first progressive disease (PD) or death. Per the RECIST criteria, definitions were as follows: CR was defined as the disappearance of all target or non-target lesions. Any pathological lymph nodes for target lesions or all lymph nodes for non-target lesions were non-pathological morphologically that was reduced in size in short axis to \<10 mm. Analysis was performed by using Kaplan-Meier method.

Outcome measures

Outcome measures
Measure	S-1+Cisplatin n=67 Participants Participants received S-1 25 mg/m\^2 orally BID every 12 hours from Day 1 through Day 21, 1 hour before or after meal with a glass of water; followed by a 7-day rest period from Day 22 to Day 28 in a 28-day cycle. Participants received a single dose of cisplatin 75 mg/m\^2 as a 1- to 3-hour IV infusion on Day 1 following the morning dose of S-1 for a maximum of 8 cycles (each cycle of 28 days). Participants received study medication until PD, AE, withdrawal of consent, or other reason for discontinuation, whichever happened earlier.	5FU+Cisplatin n=18 Participants Participants received 5-FU 800 mg/m\^2 per 24 hours as continuous IV infusion over 120 hours from Day 1 through Day 5 followed by a 16-day rest period on Days 6 through 21 in a 21-day cycle. Participants received a single dose of cisplatin 80 mg/m\^2 as a 1- to 3-hour IV infusion on Day 1 prior to the start of the 5-FU infusion on Day 1 for a maximum of 8 cycles (each cycle of 21 days). Participants received study medication until PD, AE, withdrawal of consent, or other reason for discontinuation, whichever happened earlier.
Duration of Response (DR)	5.1 months Interval 3.0 to 5.8	4.2 months Interval 2.0 to 6.0

SECONDARY outcome

Timeframe: From date of first study medication until cut-off date: 07 March 2014 (approximately 34.7 months)

Population: Analysis was performed on the ITT population. Here, 'overall number of participants analyzed' signifies participants with available data for the outcome measure.

TTR was defined as the time (in months) from the date of randomization to the date of first observation of response (PR or CR) (whichever status was recorded first). TTR was assessed based on investigator assessment utilizing RECIST 1.1. CR was defined as the disappearance of all target or non-target lesions. Any pathological lymph nodes for target lesions or all lymph nodes for non-target lesions were non-pathological morphologically that was reduced in size in short axis to \<10 mm. PR was defined as target lesions with at least 30% decrease in the sum of diameters, taking baseline sum diameters as reference. Analysis was performed by using Kaplan-Meier method.

Outcome measures

Outcome measures
Measure	S-1+Cisplatin n=67 Participants Participants received S-1 25 mg/m\^2 orally BID every 12 hours from Day 1 through Day 21, 1 hour before or after meal with a glass of water; followed by a 7-day rest period from Day 22 to Day 28 in a 28-day cycle. Participants received a single dose of cisplatin 75 mg/m\^2 as a 1- to 3-hour IV infusion on Day 1 following the morning dose of S-1 for a maximum of 8 cycles (each cycle of 28 days). Participants received study medication until PD, AE, withdrawal of consent, or other reason for discontinuation, whichever happened earlier.	5FU+Cisplatin n=18 Participants Participants received 5-FU 800 mg/m\^2 per 24 hours as continuous IV infusion over 120 hours from Day 1 through Day 5 followed by a 16-day rest period on Days 6 through 21 in a 21-day cycle. Participants received a single dose of cisplatin 80 mg/m\^2 as a 1- to 3-hour IV infusion on Day 1 prior to the start of the 5-FU infusion on Day 1 for a maximum of 8 cycles (each cycle of 21 days). Participants received study medication until PD, AE, withdrawal of consent, or other reason for discontinuation, whichever happened earlier.
Time to Tumor Response (TTR)	1.8 months Interval 1.8 to 1.9	1.9 months Interval 1.8 to 2.1

Adverse Events

S-1+Cisplatin

Serious events: 63 serious events

Other events: 210 other events

Deaths: 173 deaths

5FU+Cisplatin

Serious events: 31 serious events

Other events: 110 other events

Deaths: 90 deaths

Serious adverse events

Other adverse events

Additional Information

Taiho

Taiho Oncology, Inc.

Phone: +1 844-878-2446

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place