Study of Trifluridine/Tipiracil (TAS-102) in Patients With Metastatic Colorectal Cancer in Asia

The primary endpoint was Overall Survival (OS), which was defined as the time from random assignment to the date of death. In the absence of confirmation of death or for patients alive at the OS cutoff date, survival time was censored at the date of last trial follow-up or the cutoff date, whichever was earlier.

Time frame: Every 8 weeks. Survival status should be collected for up to 12 months after the last patient is randomized or until the target number of events (deaths) is met, whichever is later.

Population: The intent-to-treat (ITT) population: the ITT population was comprised of all patients who were randomized to study medication.

The assessment of DCR paralleled that of ORR, with DCR defined as the proportion of patients with objective evidence of CR, PR, or SD.

Time frame: From randomization until the date of radiologic disease progression, permanent discontinuation of study treatment, or death due to any cause, assessed up to 30 months.

Population: The tumor response evaluable (TR) population: the TR population included all patients in the ITT population who had measurable disease (at least 1 target lesion) at baseline and with at least 1 tumor evaluation while on treatment.

Duration of response was derived for those patients with objective evidence of PR or CR. Duration of response was defined as the time from the first documentation of response (CR or PR) to the first documentation of objective tumor progression or to death due to any cause. Patients alive and progression free as of the analysis cut-off date were censored at their last evaluable tumor response assessment prior to initiation of any non-study cancer treatment.

Time frame: From randomization until the date of radiologic disease progression, permanent discontinuation of study treatment, or death due to any cause, assessed up to 30 months.

Population: The tumor response evaluable (TR) population: the TR population included all patients in the ITT population who had measurable disease (at least 1 target lesion) at baseline and with at least 1 tumor evaluation while on treatment.

The assessment of ORR was based on Investigator review of the images according to RECIST Version 1.1. Overall response rate was defined as the proportion of patients with objective evidence of complete response (CR) or partial response (PR). At the analysis stage, the best overall response was assigned for each patient as the best response recorded from all responses recorded after study randomization. If applicable, responses recorded after disease progression or initiation of non-study cancer treatment was excluded. A patient's best response assignment of stable disease (SD) needed to be maintained for at least 6 weeks after study randomization. If a patient didn't meet this condition, best response was assigned Not evaluable.

Time frame: From randomization until the date of radiologic disease progression, permanent discontinuation of study treatment, or death due to any cause, assessed up to 30 months.

Population: The tumor response evaluable (TR) population: the TR population included all patients in the ITT population who had measurable disease (at least 1 target lesion) at baseline and with at least 1 tumor evaluation while on treatment.

The primary end point was OS, which was defined as the time from random assignment to the date of death. In the absence of confirmation of death or for patients alive at the OS cutoff date, survival time was censored at the date of last trial follow-up or the cutoff date, whichever was earlier. The OS indicated above as secondary outcome was analyzed by mutant type KRAS.

Time frame: Every 8 weeks. Survival status should be collected for up to 12 months after the last patient is randomized or until the target number of events (deaths) is met, whichever is later.

Population: The intent-to-treat (ITT) population: the ITT population was comprised of all patients who were randomized to study medication.

The primary end point was OS, which was defined as the time from random assignment to the date of death. In the absence of confirmation of death or for patients alive at the OS cutoff date, survival time was censored at the date of last trial follow-up or the cutoff date, whichever was earlier. The OS indicated above as secondary outcome was analyzed by wild type KRAS.

Time frame: Every 8 weeks. Survival status should be collected for up to 12 months after the last patient is randomized or until the target number of events (deaths) is met, whichever is later.

Population: The intent-to-treat (ITT) population: the ITT population was comprised of all patients who were randomized to study medication.

Tumor assessments were performed throughout the study period and analyzed using Response Evaluation Criteria in Solid Tumors criteria (Version 1.1, 2009). Progression-free survival was defined as the time (in months) from the date of randomization until the date of the Investigator-assessed radiological disease progression or death due to any cause. Patients who received non-study cancer treatment before radiologic evidence of disease progression were censored at the date of the last evaluable tumor assessment before initiation of non-study cancer treatment.

Time frame: Every 8 weeks. Tumor assessments will be performed until radiologic progression develops or the start of new anticancer treatment, for up to 12 months after the last patient is randomized or until the target number of events (deaths) is met.

Population: The intent-to-treat (ITT) population: the ITT population was comprised of all patients who were randomized to study medication.

Progression-free survival was defined as the time (in months) from the date of randomization until the date of the Investigator-assessed radiological disease progression or death due to any cause. Patients who received non-study cancer treatment before radiologic evidence of disease progression were censored at the date of the last evaluable tumor assessment before initiation of non-study cancer treatment. The PFS indicated above as secondary outcome was analyzed by mutant type KRAS.

Time frame: Every 8 weeks. Tumor assessments will be performed until radiologic progression develops or the start of new anticancer treatment, for up to 12 months after the last patient is randomized or until the target number of events (deaths) is met.

Population: The intent-to-treat (ITT) population: the ITT population was comprised of all patients who were randomized to study medication.

Progression-free survival was defined as the time (in months) from the date of randomization until the date of the Investigator-assessed radiological disease progression or death due to any cause. Patients who received non-study cancer treatment before radiologic evidence of disease progression were censored at the date of the last evaluable tumor assessment before initiation of non-study cancer treatment. The PFS indicated above as secondary outcome was analyzed by wild type KRAS.

Time frame: Every 8 weeks. Tumor assessments will be performed until radiologic progression develops or the start of new anticancer treatment, for up to 12 months after the last patient is randomized or until the target number of events (deaths) is met.

Population: The intent-to-treat (ITT) population: the ITT population was comprised of all patients who were randomized to study medication.

An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Treatment-related AEs were events between administration of study drug and up to 30 Days that were absent before treatment or that worsened relative to pre-treatment state. A serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability /incapacity; congenital anomaly. The AEs were graded for severity using National Cancer Institute Common Terminology Criteria for AEs.

Time frame: From the time a patient signed informed until 30 day safety follow-up visit or until initiation of new anticancer treatment, or assessed up to 30 months.

Population: The as-treated (AT) population: the AT population contained all patients in the ITT population who received at least 1 dose of study medication and patients were analyzed according to treatment actually received.

All laboratory values that were out of the normal range were to be evaluated for their clinical significance before exposing the patient to the next dose of study medication. Any laboratory abnormality that was clinically significant, e.g., results in delay of study medication dosing, study discontinuation, required treatment due to abnormal values, or was considered by the Investigator to be medical important, were to be reported as an AE, unless it was considered part of clinical manifestations to a clinical diagnosis that has already been reported as an AE.

Time frame: From the time a patient signed informed until 30 day safety follow-up visit or until initiation of new anticancer treatment, or assessed up to 30 months.

Population: The as-treated (AT) population: the AT population contained all patients in the ITT population who received at least 1 dose of study medication and patients were analyzed according to treatment actually received.

Time to treatment failure was defined as the time (in months) from the date of randomization until the date of radiologic disease progression, permanent discontinuation of study treatment, or death due to any cause. Censoring for TTF was also applied for those patients who were given non-study cancer treatment, with censoring at the time when the patient began the non-study cancer treatment.

Time frame: From randomization until the date of radiologic disease progression, permanent discontinuation of study treatment, or death due to any cause, assessed up to 30 months.

Population: The intent-to-treat (ITT) population: the ITT population was comprised of all patients who were randomized to study medication.