A Trial of ABI-007 Versus Dacarbazine in Previously Untreated Patients With Metastatic Malignant Melanoma

PFS was defined as the time from the randomization date to the start of disease progression or patient death, whichever occurred first. Participants who did not have disease progression or had not died were censored at the last known time that the patient was progression free. In the event of palliative radiotherapy or surgery, they were censored at the last assessment where they were documented to be progression-free prior to the date of radiotherapy or surgery. In follow up, participants who began new anticancer therapy prior to documented progression were censored at the last assessment where they were documented as progression free. Those with two or more missing response assessments prior to a visit with documented disease progression (or death) were censored at the last visit where they were documented to be progression free. RECIST defines progressive disease as a ≥ 20% increase taking as reference the smallest sum of the longest diameters recorded since the treatment began.

Time frame: Response assessment completed every 8 weeks until disease progression for up to 106 weeks; data cut off 30 June 2012

Population: Intent to treat population = The ITT population consisted of all randomized participants regardless of whether the participant received any study drug or had any efficacy assessments collected.

Maximal degree of myelosuppression was represented by the nadir in platelet count measurements over all treatment cycles.

Time frame: Day 1 up to 106 weeks; up to data cut off 30 June 2012

Population: Treated population = consisted of all randomized participants who received at least one dose of study drug and with at least one post-baseline central laboratory result were included

Maximal degree of myelosuppression during study drug dosing was represented by the nadir in ANC measurements over all treatment cycles.

Time frame: Day 1 up to 106 weeks; up to data cut off 30 June 2012

Population: Treated Population = consisted of all randomized participants who received at least one dose of study drug and with at least one post-baseline central laboratory result were included

Maximal degree of myelosuppression during study drug dosing was represented by the nadir in hemoglobin count measurements over all treatment cycles.

Time frame: Day 1 up to 106 weeks; up to data cut off 30 June 2012

Population: Treated population = consisted of all randomized participants who received at least one dose of study drug and with at least one post-baseline central laboratory result were included.

Maximal degree of myelosuppression was represented by the nadir in white blood cells (WBCs) count measurements over all treatment cycles.

Time frame: Day 1 up to 106 weeks; up to data cut off 30 June 2012

Population: Treated population = consisted of all randomized participants who received at least one dose of study drug and with at least one post-baseline central laboratory result were included

The number of participants with dose reductions, dose interruptions and dose delays that occurred during the treatment period. Dose reductions, interruptions and delays are typically caused by clinically significant laboratory abnormalities and /or treatment emergent adverse events/toxicities.

Time frame: Maximum study drug exposure 106 weeks; data cut off 30 June 2012

Population: Treated population

Survival was defined as the time from the date of randomization to the date of death (any cause). Participants were censored at the last known time that they were alive.

Time frame: Up to 38 months; Up to data cut off of 30 June 2012

Population: Intent to treat population

Time frame: On Cycle 1, Day 1 blood samples were taken at 0.25, 3.5, and 24 hr post-infusion end of the initial dose

Population: Patients randomized to receive ABI-007 treatment in Australia, Canada, Europe, United Kingdom and United States had the option to participate in sparse PK sampling in this study. Only 44 participants consented to participate, an insufficient number to support the planned population PK analysis hence these analyses were not performed

A Treatment Emergent AE (TEAE) was any AE that began or worsened after the start of the study drug through 30 days after the last dose of study drug or end of study whichever is later. A treatment related toxicity was one considered by the investigator to be possibly, probably or definitely related to study drug. AE's were graded according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) V 3.0 criteria and the following scale: Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life threatening, and Grade 5 = Death A SAE is any untoward medical occurrence at any dose that is fatal or life threatening, results in persistent or significant disability or incapacity; requires prolonged hospitalizations; is a congenital anomaly birth defect in the offspring of a patient, and conditions not included in the above that may jeopardize the patient or may require intervention to prevent one of the outcomes listed above.

Time frame: Maximum exposure to study drug was 106 weeks; up to data cut off of 30 June 2012

Population: Treated Population = The Treated population consisted of all randomized participants who received at least one dose of study drug

Duration of response (DOR) as measured by PFS based on radiological review for participants who achieved an objective confirmed response of CR or PR. DOR was defined as progression-free survival in responders, i.e. as the time between the start of a complete response (CR) or partial response (PR) and the start of progressive disease (PD) or participants death from any cause, whichever occurred first. Participants that did not have progression or had not died were censored at the last known time the participant was progression free. Participants that had initiated other anticancer therapy prior to progression were censored at the time when new anticancer therapy was initiated. Complete response (CR) and partial response (PR) are defined in outcome #4. Progressive disease was defined as at least a 20% increase in the sum of the longest diameters of target lesions; or the appearance of one or more new lesions; or the unequivocal progression of a non-target lesion.

Time frame: up to data cut off 30 June 2012

Population: ITT of participants with a confirmed complete or partial overall response

RECIST defines complete response (CR): The disappearance of all known disease and no new sites or disease related symptoms confirmed at least 4 weeks after initial documentation. All sites must be assessed, including non-measurable sites, such as effusions, or markers. Disappearance of all non-target lesions. The normalization of tumor marker level confirmed at least 4 weeks after initial documentation. Partial response (PR): At least a 30% decrease in the sum of the longest diameters of target lesions, taking as a reference the baseline sum of the longest diameters confirmed at least 4 weeks after initial documentation. PR is also recorded when all measurable disease has completely disappeared, but a non-measurable component (i.e., ascites) is still present but not progressing. As well as persistence of one or more non-target lesion(s) and/or the maintenance of tumor marker level above the normal limits.

Time frame: every 8 weeks; up to data cut off 30 June 2012

Population: ITT

Disease control is stable disease (SD) for \>=16 weeks + complete response (CR) + partial response (PR). See Outcome #4 for definitions of CR and PR. RECIST defines SD for target lesions as neither sufficient shrinkage to qualify for partial response nor sufficient increase to qualify for progressive disease, no occurrence of progression disease for non-target lesions, and no new lesions.

Time frame: Response assessment completed every 8 weeks until disease progression; up to data cut-off 30 June 2012

Population: ITT

PFS was defined as the time from the randomization date to the start of disease progression or patient death, whichever occurred first. Participants who did not have disease progression or had not died were censored at the last known time that the patient was progression free. In the event of palliative radiotherapy or surgery, they were censored at the last assessment where they were documented to be progression-free prior to the date of radiotherapy or surgery. In follow up, patients who began new anticancer therapy prior to documented progression were censored at the last assessment where they were documented as progression free. Those with two or more missing response assessments prior to a visit with documented disease progression (or death) were censored at the last visit where they were documented to be progression free.

Time frame: Response assessments completed every 8 weeks until disease progression; up to data cut off 30 June 2012; 38 months

Population: ITT