ASPECCT: A Study of Panitumumab Efficacy and Safety Compared to Cetuximab in Patients With KRAS Wild-Type Metastatic Colorectal Cancer

Overall survival is the time from the date of randomization until the date of death. Participants who had not died by the analysis data cut-off date were censored at their last contact date.

Time frame: From randomization until the data cut-off date of 5 February 2013. Maximum time on study was 155 weeks.

Population: Primary Analysis Set: All participants who were randomized and who received at least 1 dose of panitumumab or cetuximab; analyzed according to randomized treatment arm.

The EQ-5D is a standardized instrument for use as a generic measure of health outcome. The health state index measures the following 5 health dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension contains 3 levels of response to reflect degree of problems participants have experienced: no problem (1), some problem (2) and extreme problems (3). The health states for each respondent are converted into a single index number using a specified set of weights. Resulting scores can range from 1.0 and -0.594. A higher score indicates a more preferred health status with 1.0 representing perfect health and 0 representing death. Negative scores are possible and represent health states regarded as less preferable than death (0). Repeated measures mixed model includes treatment, geographic region, ECOG score, assessment week, and treatment by assessment week interaction as fixed effects, and participants a random effect.

Time frame: From Study Day 1 through the last day of treatment or disease progression, up to Week 85.

Population: Patient reported outcomes (PRO) analysis set: all participants in the primary analysis set who have a Baseline and at least one follow-up PRO assessment prior to clinical or objective disease progression per RECIST version 1.1. Participants with available data are included.

The EQ-5D is a standardized instrument for use as a generic measure of health outcome. The VAS asks respondents to rate their present health status on a 0 - 100 scale, with 0 labeled as Worst imaginable health state and 100 labeled as Best imaginable health state. The VAS score is determined by observing the point at which the participant's hand drawn line intersects the scale.

Time frame: From Study Day 1 through the last day of treatment or disease progression, up to Week 85.

Population: Patient reported outcomes (PRO) analysis set participants with available data

The FCSI consists of 9 questions comprising the most important symptoms associated with colorectal cancer, including energy, pain, weight, diarrhea, nausea, swelling or cramps in the stomach area, appetite, ability to enjoy life, and overall quality of life. The 9 questions are combined in three algorithms to provide information for 3 domains: colorectal cancer symptoms, physical well-being, and functional well-being. Each of the 9 items are scored from 0 to 4 representing Not at All through to Very Much True. The raw score for all items is transformed to a 0-100 scale, and the average for each of the 3 subscales is calculated; high scores illustrate an improved state (e.g. able to enjoy life more).

Time frame: From Study Day 1 through the last day of treatment or disease progression, up to Week 85.

Population: Patient reported outcomes (PRO) analysis set participants with available data.

The FCSI consists of 9 questions comprising the most important symptoms associated with colorectal cancer, including energy, pain, weight, diarrhea, nausea, swelling or cramps in the stomach area, appetite, ability to enjoy life, and overall quality of life. The 9 questions are combined in three algorithms to provide information for 3 domains: colorectal cancer symptoms, physical well-being, and functional well-being. Each of the 9 items are scored from 0 to 4 representing Not at All through to Very Much True. The raw score for all items is transformed to a 0-100 scale, and the average for each of the 3 subscales is calculated; high scores illustrate an improved state (e.g. able to enjoy life more).

Time frame: From Study Day 1 through the last day of treatment or disease progression, up to Week 85.

Population: Patient reported outcomes (PRO) analysis set participants with available data.

The FCSI consists of 9 questions comprising the most important symptoms associated with colorectal cancer, including energy, pain, weight, diarrhea, nausea, swelling or cramps in the stomach area, appetite, ability to enjoy life, and overall quality of life. The 9 questions are combined in three algorithms to provide information for 3 domains: colorectal cancer symptoms, physical well-being, and functional well-being. Each of the 9 items are scored from 0 to 4 representing Not at All through to Very Much True. The raw score for all items is transformed to a 0-100 scale, and the average for each of the 3 subscales is calculated; high scores illustrate an improved state (e.g. able to enjoy life more).

Time frame: From Study Day 1 through the last day of treatment or disease progression, up to Week 85.

Population: Patient reported outcomes (PRO) analysis set participants with available data.

Duration of response (DOR), calculated only for those participants with an objective response, is the time from first objective response to disease progression per the RECIST v1.1 or death. Participants not meeting criteria for progression or who died by the analysis data cutoff date were censored at their last evaluable disease assessment date.

Time frame: From randomization until the data cut-off date of 5 February 2013. Maximum time on study was 155 weeks.

Population: Participants with an objective response

Serious adverse events include any event that is fatal, life threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, a congenital anomaly/birth defect, or other significant medical hazard. Treatment-related AEs are those the investigator considered as a reasonable possibility to have been caused by study drug.

Time frame: From the day of the first dose of study therapy through 30 days since the last dose. Maximum time on study treatment was 130 weeks.

Population: Safety Analysis Set (randomized participants who received at least 1 dose of study medication). Five participants who received the incorrect study medication (4 assigned to panitumumab but received cetuximab and 1 assigned to cetuximab but received panitumumab) were included in different treatment arms for safety analyses.

Objective response is either a complete response (CR) or partial response (PR) per RECIST version 1.1. All participants that did not meet the criteria for an objective response by the analysis cut-off date were considered non-responders. CR: Disappearance of all target lesions, any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm, and disappearance of all non-target lesions, and no new lesions. PR: Disappearance of all target lesions, persistence of one or more non-target lesions not qualifying for either CR or progressive disease, or, at least a 30% decrease in the sum of diameters of target lesions with no unequivocal progression of existing non-target lesions and no new lesions.

Time frame: From randomization until the data cut-off date of 5 February 2013. Maximum time on study was 155 weeks.

Population: Tumor Response Analysis Set: Participants in the primary analysis set with at least 1 Baseline unidimensionally measurable lesion per RECIST version 1.1.

Progression free survival (PFS) is the time from the date of randomization to the date of disease progression per the Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1 or death. Participants alive and not meeting criteria for progression by the analysis data cut-off date were censored at their last evaluable disease assessment date. Progression is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study based on all target lesions recorded since the treatment started (the sum must also demonstrate an absolute increase of at least 5 mm), or unequivocal progression of existing non-target lesions, or any new lesions.

Time frame: From randomization until the data cut-off date of 5 February 2013. Maximum time on study was 155 weeks.

Population: Primary analysis set

Time to response (TTR), calculated for those participants with an objective response, is defined as the time from the randomization date to the date of first objective response.

Time frame: From randomization until the data cut-off date of 5 February 2013. Maximum time on study was 155 weeks.

Population: Participants with an objective response

Time to treatment failure (TTF) is the time from randomization date to date that the decision was made to end the treatment period for any reason; participants who remained in the treatment period at the time of analysis were censored at the date of the last on-study assessment.

Time frame: From randomization until the data cut-off date of 5 February 2013. Maximum time on study was 155 weeks.

Population: Primary analysis set