A Double-blind Study of Paclitaxel in Combination With Reparixin or Placebo for Metastatic Triple-Negative Breast Cancer

PFS was defined as the number of days between the date of randomization and the date of clinical disease progression, according to RECIST criteria version 1.1, as assessed by Independent Radiology Review, or to death due to any cause, whichever occurred first. Patients must have completed at least one course of treatment and performed at least one disease assessment to be considered evaluable for response.

Time frame: Baseline up to every 8 weeks until disease progression or death, whichever occurs first, up to 721 days

Population: The Intent-to-Treat (ITT) Population consisted of all patients who are randomized and was based upon the randomized treatment, regardless of the treatment actually received. Patients were in the ITT analysis whether or not they received study drug. The primary and secondary efficacy analyses were presented primarily for the ITT Population.

BOR is defined as the best response among all overall responses (in the order complete response \[CR\], partial response \[PR\], stable disease \[SD\], and progressive disease \[PD\]) recorded as an independent review response from the start of reparixin or placebo until disease progression/recurrence or end of treatment, or death, whichever comes first. The status of BOR of PR or CR needs to be confirmed by repeat tumor assessment within no less than 4 weeks according to RECIST version 1.1. Complete Response (CR) = Disappearance of all target lesions; Partial Response (PR) = \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. If the status of CR or PR cannot be confirmed by repeat tumor assessment, the best overall response of unconfirmed CR and PR will be PR and SD, respectively. Patients must have completed at least one course of treatment and performed at least one disease assessment to be considered evaluable for response.

Time frame: From the start of treatment, every 8 weeks, up to 56 months

Population: The Response-Evaluable Population consisted of all patients who had completed at least one cycle of treatment and had a baseline assessment and have undergone at least one post-baseline disease assessment.

Duration of overall response (DOR) in days for the investigator assessments is measured from the time response criteria are first met for CR or PR (whichever is first recorded on the Disease Response page on the CRF) until either death or the first date that recurrent or PD is objectively documented (on the Disease Response p. on the CRF or the Follow-Up Disease Evaluation page indicates disease progression and there is supporting information in the Disease Status pages) per RECIST version 1.1. Complete Response (CR) = Disappearance of all target lesions; Partial Response (PR) = \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. If a patient is lost to follow-up with no documentation of PD, DOR was censored at the last evaluable tumor assessment. DOR was calculated only for responding patients (PR or CR) as recorded on the CRF page Disease Response based upon the RECIST version 1.1. Duration of overall response wa

Time frame: Baseline up to every 8 weeks until documented disease progression, up to 557 days

Population: The Response-Evaluable Population consisted of all patients who had completed at least one cycle of treatment and had a baseline assessment and have undergone at least one post-baseline disease assessment.

PFS was defined as the time from randomization to first documentation of disease progression, according to RECIST criteria version 1.1, as assessed by Independent Radiology Review, or to death due to any cause, whichever occurred first. For each treatment group, the Kaplan-Meier estimates for the median PFS time, the first and third quartiles were presented, along with approximate 95% confidence intervals if there were a sufficient number of progressions or deaths. Patients must have completed at least one course of treatment and performed at least one disease assessment to be considered evaluable for response.

Time frame: At screening and every 8 weeks, up to 721 days

Population: The Intent-to-Treat (ITT) Population consisted of all patients who are randomized and was based upon the randomized treatment, regardless of the treatment actually received. Patients were in the ITT analysis whether or not they received study drug. The primary and secondary efficacy analyses were presented primarily for the ITT Population.

Treatment-emergent adverse events (TEAEs) are those which first occur or increase in severity or relationship to study drug after the first dose of study drug and before 30 days after the last dose of study treatment, reparixin/placebo. In the case of missing or partial dates, any AE that could have started on or after first dose date was assumed to be treatment-emergent. In the case of missing or partial dates, imputed dates (see section 10.1 AE date imputation) were used.

Time frame: Throughout the study, until off-treatment visit (performed 14 to 28 days following the last dose of study drug), up to 985 days

Population: Safety population: this population consisted of all patients who had taken at least one dose of the study treatment and was based upon the treatment they actually received.

The ORR was defined as the percentage of patients achieving CR or PR in the Evaluable Population. The response rate was calculated from the independently reviewed assessment best response. In case of PR or CR, only confirmed cases were considered to be responses. Complete Response (CR) = Disappearance of all target lesions; Partial Response (PR) = \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. Patients with unknown or missing response, including response of not all evaluated or unable to determine, were treated as non-responders; i.e., they were included in the denominator when calculating the percentages. Patients must have completed at least one course of treatment and performed at least one disease assessment to be considered evaluable for response.

Time frame: Baseline up to every 8 weeks until documented disease progression, up to 56 months

Population: Responsible-evaluable population: this population consisted of all patients who had completed at least one cycle of treatment and had a baseline assessment and have undergone at least one post-baseline disease assessment.

OS was defined as the time from randomization until death due to any cause. For patients who did not die, time of death was censored at the date of last contact. Patients must have completed at least one course of treatment and performed at least one disease assessment to be considered evaluable for response.

Time frame: Baseline until death due to any cause, up to 985 days

Population: The Intent-to-Treat (ITT) Population consisted of all patients who are randomized and was based upon the randomized treatment, regardless of the treatment actually received. Patients were in the ITT analysis whether or not they received study drug. The primary and secondary efficacy analyses were presented primarily for the ITT Population.

A serious adverse event (SAE) in human drug trials is defined as any untoward medical occurrence that at any dose 1. \- results in death, (fatal) 2. \- is life-threatening 3. \- requires inpatient hospitalization or causes prolongation of existing hospitalization 4. \- results in persistent or significant disability/incapacity, 5. \- may have caused a congenital anomaly/birth defect, or 6. \- requires intervention to prevent permanent impairment or damage.

Time frame: Throughout the study, until off-treatment visit (performed 14 to 28 days following the last dose of study drug), up to 985 days.

Population: Safety population: this population consisted of all patients who had taken at least one dose of the study treatment and was based upon the treatment they actually received.