Trial Outcomes & Findings for Skin Toxicity Treatment in Metastatic Colorectal Cancer (mCRC) Patients Receiving Panitumumab + Irinotecan-based Therapy (NCT NCT00332163)

Last Updated: 2016-02-23

Results Overview

Skin toxicities were assessed by the study clinician and graded according to the modified Common Toxicity Criteria for Adverse Events (CTCAE) v.3.0 Dermatology Toxicity Grading criteria, on a scale from Grade 1 (mild) to 4 (life-threatening). The specific skin toxicities of interest were pruritus, acneiform dermatitis, skin desquamation (also described as skin exfoliation), exfoliative dermatitis, paronychia, nail disorder, skin fissures, skin laceration, pruritic rash, pustular rash, skin infection, skin ulceration, and local infection.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

95 participants

Primary outcome timeframe

6 weeks

Results posted on

2016-02-23

Participant Flow

Participants enrolled at 36 sites in the United States between 17 April 2006 and 28 September 2007.

Participants were stratified to receive either a FOLFIRI and panitumumab regimen or an irinotecan and panitumumab regimen based on the investigator's discretion according to local standard of care. Participants were then randomized to receive either a pre-emptive skin treatment or reactive skin treatment regimen for a 6-week skin treatment period.

Participant milestones

Participant milestones
Measure	Pre-emptive Skin Treatment Participants received either FOLFIRI and panitumumab 6 mg/kg once every 2 weeks (Q2W) or irinotecan and panitumumab 9 mg/kg once every 3 weeks (Q3W), and pre-emptive skin treatment which included skin moisturizer, sunscreen, 1% hydrocortisone cream, and an oral antibiotic for 6 weeks starting 24 hours prior to chemotherapy.	Reactive Skin Treatment Participants received either FOLFIRI and panitumumab 6 mg/kg Q2W or irinotecan and panitumumab 9 mg/kg Q3W. Participants were treated for each individual skin toxicity occurrence according to prespecified guidelines and based on the type and severity. Treatment could include emollient, sunscreen, topical or oral steroids, antibiotics, or antihistamines, as required.
Overall Study STARTED	48	47
Overall Study Received Treatment	48	47
Overall Study COMPLETED	48	47
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Skin Toxicity Treatment in Metastatic Colorectal Cancer (mCRC) Patients Receiving Panitumumab + Irinotecan-based Therapy

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Pre-emptive Skin Treatment n=48 Participants Participants received either FOLFIRI and panitumumab 6 mg/kg once every 2 weeks (Q2W) or irinotecan and panitumumab 9 mg/kg once every 3 weeks (Q3W), and pre-emptive skin treatment which included skin moisturizer, sunscreen, 1% hydrocortisone cream, and an oral antibiotic for 6 weeks starting 24 hours prior to chemotherapy.	Reactive Skin Treatment n=47 Participants Participants received either FOLFIRI and panitumumab 6 mg/kg Q2W or irinotecan and panitumumab 9 mg/kg Q3W. Participants were treated for each individual skin toxicity occurrence according to prespecified guidelines and based on the type and severity. Treatment could include emollient, sunscreen, topical or oral steroids, antibiotics, or antihistamines, as required.	Total n=95 Participants Total of all reporting groups
Age, Continuous	60.6 years STANDARD_DEVIATION 12.7 • n=5 Participants	61.1 years STANDARD_DEVIATION 9.9 • n=7 Participants	60.8 years STANDARD_DEVIATION 11.4 • n=5 Participants
Sex: Female, Male Female	16 Participants n=5 Participants	21 Participants n=7 Participants	37 Participants n=5 Participants
Sex: Female, Male Male	32 Participants n=5 Participants	26 Participants n=7 Participants	58 Participants n=5 Participants
Race/Ethnicity, Customized White or Caucasian	34 participants n=5 Participants	40 participants n=7 Participants	74 participants n=5 Participants
Race/Ethnicity, Customized Black or African American	6 participants n=5 Participants	5 participants n=7 Participants	11 participants n=5 Participants
Race/Ethnicity, Customized Hispanic or Latino	5 participants n=5 Participants	1 participants n=7 Participants	6 participants n=5 Participants
Race/Ethnicity, Customized Asian	2 participants n=5 Participants	0 participants n=7 Participants	2 participants n=5 Participants
Race/Ethnicity, Customized Native Hawaiian or other Pacific Islander	1 participants n=5 Participants	0 participants n=7 Participants	1 participants n=5 Participants
Race/Ethnicity, Customized Other	0 participants n=5 Participants	1 participants n=7 Participants	1 participants n=5 Participants
Chemotherapy Stratification FOLFIRI + Panitumumab Q2W	28 participants n=5 Participants	27 participants n=7 Participants	55 participants n=5 Participants
Chemotherapy Stratification Irinotecan + Panitumumab Q3W	20 participants n=5 Participants	20 participants n=7 Participants	40 participants n=5 Participants

PRIMARY outcome

Timeframe: 6 weeks

Population: Primary analysis set (all randomized participants who provided informed consent before protocol-specific procedures and who received at least 1 dose of panitumumab)

Outcome measures

Outcome measures
Measure	Pre-emptive Skin Treatment n=48 Participants Participants received either FOLFIRI and panitumumab 6 mg/kg once every 2 weeks (Q2W) or irinotecan and panitumumab 9 mg/kg once every 3 weeks (Q3W), and pre-emptive skin treatment which included skin moisturizer, sunscreen, 1% hydrocortisone cream, and an oral antibiotic for 6 weeks starting 24 hours prior to chemotherapy.	Reactive Skin Treatment n=47 Participants Participants received either FOLFIRI and panitumumab 6 mg/kg Q2W or irinotecan and panitumumab 9 mg/kg Q3W. Participants were treated for each individual skin toxicity occurrence according to prespecified guidelines and based on the type and severity. Treatment could include emollient, sunscreen, topical or oral steroids, antibiotics, or antihistamines, as required.
Percentage of Participants With Specific Grade 2 or Higher Skin Toxicities During the 6-week Skin Treatment Period	29 percentage of participants Interval 16.0 to 42.0	62 percentage of participants Interval 48.0 to 76.0

SECONDARY outcome

Timeframe: 6 weeks

Population: Primary Analysis Set

The percentage of participants who developed at least 1 incidence of ≥ grade 2 skin toxicities of any type during the 6-week skin treatment period. Analysis of this endpoint was based on adverse event data associated with the "Skin and Subcutaneous Tissue Disorders" system organ class. Adverse events were graded according to the National Cancer Institute (NCI) CTCAE version 3.0.

Outcome measures

Outcome measures
Measure	Pre-emptive Skin Treatment n=48 Participants Participants received either FOLFIRI and panitumumab 6 mg/kg once every 2 weeks (Q2W) or irinotecan and panitumumab 9 mg/kg once every 3 weeks (Q3W), and pre-emptive skin treatment which included skin moisturizer, sunscreen, 1% hydrocortisone cream, and an oral antibiotic for 6 weeks starting 24 hours prior to chemotherapy.	Reactive Skin Treatment n=47 Participants Participants received either FOLFIRI and panitumumab 6 mg/kg Q2W or irinotecan and panitumumab 9 mg/kg Q3W. Participants were treated for each individual skin toxicity occurrence according to prespecified guidelines and based on the type and severity. Treatment could include emollient, sunscreen, topical or oral steroids, antibiotics, or antihistamines, as required.
Percentage of Participants With Any Grade 2 or Higher Skin Toxicity of Any Type During the 6-week Skin Treatment Period	40 percentage of participants Interval 26.0 to 53.0	62 percentage of participants Interval 48.0 to 76.0

SECONDARY outcome

Timeframe: 6 weeks

Population: Primary Analysis Set

The time to the first occurrence of specific grade 2 or higher skin toxicities of interest was defined as the time from the first dose of panitumumab to the date of first occurrence of specific ≥ grade 2 skin toxicities of interest. Participants who did not experience specific skin-related toxicities were censored at their last skin toxicity assessment during the skin toxicity assessment period. Skin toxicities were assessed by the study clinician and graded according to the modified CTCAE v.3.0 Dermatology Toxicity Grading criteria, on a scale from Grade 1 (mild) to 4 (life-threatening). The specific skin toxicities of interest were pruritus, acneiform dermatitis, skin desquamation (also described as skin exfoliation), exfoliative dermatitis, paronychia, nail disorder, skin fissures, skin laceration, pruritic rash, pustular rash, skin infection, skin ulceration, and local infection.

Outcome measures

Outcome measures
Measure	Pre-emptive Skin Treatment n=48 Participants Participants received either FOLFIRI and panitumumab 6 mg/kg once every 2 weeks (Q2W) or irinotecan and panitumumab 9 mg/kg once every 3 weeks (Q3W), and pre-emptive skin treatment which included skin moisturizer, sunscreen, 1% hydrocortisone cream, and an oral antibiotic for 6 weeks starting 24 hours prior to chemotherapy.	Reactive Skin Treatment n=47 Participants Participants received either FOLFIRI and panitumumab 6 mg/kg Q2W or irinotecan and panitumumab 9 mg/kg Q3W. Participants were treated for each individual skin toxicity occurrence according to prespecified guidelines and based on the type and severity. Treatment could include emollient, sunscreen, topical or oral steroids, antibiotics, or antihistamines, as required.
Time to First Occurrence of Specific Grade 2 or Higher Skin Toxicities of Interest	NA weeks Not reached due to the low number of events	2.1 weeks Interval 2.1 to 6.3

SECONDARY outcome

Timeframe: 6 weeks

Population: Primary Analysis Set

The percentage of participants with a most severe grade of 2, 3 or 4 specific skin toxicity of interest reported during the 6-week skin treatment period. Skin toxicities were assessed by the study clinician and graded according to the modified CTCAE v.3.0 Dermatology Toxicity Grading criteria, on a scale from Grade 1 (mild) to 4 (life-threatening). The specific skin toxicities of interest were pruritus, acneiform dermatitis, skin desquamation (also described as skin exfoliation), exfoliative dermatitis, paronychia, nail disorder, skin fissures, skin laceration, pruritic rash, pustular rash, skin infection, skin ulceration, and local infection.

Outcome measures

Outcome measures
Measure	Pre-emptive Skin Treatment n=48 Participants Participants received either FOLFIRI and panitumumab 6 mg/kg once every 2 weeks (Q2W) or irinotecan and panitumumab 9 mg/kg once every 3 weeks (Q3W), and pre-emptive skin treatment which included skin moisturizer, sunscreen, 1% hydrocortisone cream, and an oral antibiotic for 6 weeks starting 24 hours prior to chemotherapy.	Reactive Skin Treatment n=47 Participants Participants received either FOLFIRI and panitumumab 6 mg/kg Q2W or irinotecan and panitumumab 9 mg/kg Q3W. Participants were treated for each individual skin toxicity occurrence according to prespecified guidelines and based on the type and severity. Treatment could include emollient, sunscreen, topical or oral steroids, antibiotics, or antihistamines, as required.
Most Severe Specific Grade 2 or Higher Skin Toxicities of Interest Grade 3	6 percentage of participants Interval 0.0 to 13.0	21 percentage of participants Interval 10.0 to 33.0
Most Severe Specific Grade 2 or Higher Skin Toxicities of Interest Grade 2	23 percentage of participants Interval 11.0 to 35.0	40 percentage of participants Interval 26.0 to 54.0
Most Severe Specific Grade 2 or Higher Skin Toxicities of Interest Grade 4	0 percentage of participants Could not be estimated as there were no events in this category	0 percentage of participants Could not be estimated as there were no events in this category

SECONDARY outcome

Timeframe: 6 weeks

Population: Primary Analysis Set

Time to the first most severe grade ≥ 2 of all the specific skin-related toxicities of interest was defined as the time from the first dose of panitumumab to the date of the first occurrence of the most severe specific ≥ grade 2 skin toxicity of interest during the 6-week skin treatment period. Participants who did not experience any specific skin-related toxicity of grade ≥ 2 were censored at their last skin toxicity assessment during the 6-week skin toxicity assessment period. Skin toxicities were assessed by the study clinician and graded according to the modified CTCAE v.3.0 Dermatology Toxicity Grading criteria, on a scale from Grade 1 (mild) to 4 (life-threatening). The specific skin toxicities of interest were pruritus, acneiform dermatitis, skin desquamation (also described as skin exfoliation), exfoliative dermatitis, paronychia, nail disorder, skin fissures, skin laceration, pruritic rash, pustular rash, skin infection, skin ulceration, and local infection.

Outcome measures

Outcome measures
Measure	Pre-emptive Skin Treatment n=48 Participants Participants received either FOLFIRI and panitumumab 6 mg/kg once every 2 weeks (Q2W) or irinotecan and panitumumab 9 mg/kg once every 3 weeks (Q3W), and pre-emptive skin treatment which included skin moisturizer, sunscreen, 1% hydrocortisone cream, and an oral antibiotic for 6 weeks starting 24 hours prior to chemotherapy.	Reactive Skin Treatment n=47 Participants Participants received either FOLFIRI and panitumumab 6 mg/kg Q2W or irinotecan and panitumumab 9 mg/kg Q3W. Participants were treated for each individual skin toxicity occurrence according to prespecified guidelines and based on the type and severity. Treatment could include emollient, sunscreen, topical or oral steroids, antibiotics, or antihistamines, as required.
Time to First Most Severe Specific Grade 2 or Higher Skin Toxicities of Interest	NA weeks Could not be estimated due to the low number of events	2.7 weeks Interval 2.1 to 6.3

SECONDARY outcome

Timeframe: 6 weeks

Population: Primary Analysis Set

Outcome measures

Outcome measures
Measure	Pre-emptive Skin Treatment n=48 Participants Participants received either FOLFIRI and panitumumab 6 mg/kg once every 2 weeks (Q2W) or irinotecan and panitumumab 9 mg/kg once every 3 weeks (Q3W), and pre-emptive skin treatment which included skin moisturizer, sunscreen, 1% hydrocortisone cream, and an oral antibiotic for 6 weeks starting 24 hours prior to chemotherapy.	Reactive Skin Treatment n=47 Participants Participants received either FOLFIRI and panitumumab 6 mg/kg Q2W or irinotecan and panitumumab 9 mg/kg Q3W. Participants were treated for each individual skin toxicity occurrence according to prespecified guidelines and based on the type and severity. Treatment could include emollient, sunscreen, topical or oral steroids, antibiotics, or antihistamines, as required.
Percentage of Participants With Panitumumab Dose Reductions Due to the Specific Skin Toxicities of Interest	6 percentage of participants Interval 0.0 to 13.0	11 percentage of participants Interval 2.0 to 19.0

SECONDARY outcome

Timeframe: Week 9 with confirmed response at Week 13 for the FOLFIRI and panitumumab Q2W regimen or at Week 10 with confirmed response at Week 14 for the irinotecan and panitumumab Q3W regimen.

Population: Primary Analysis Set; participants who discontinued prematurely without a post-baseline tumor assessment or with an observed CR or PR at Week 9 or 10 that was not confirmed at Week 13/14 were considered non-responders.

Tumor response was assessed by computed tomography (CT) scan or magnetic resonance imaging (MRI) of the abdomen, pelvis, and all other sites of disease. Disease assessments were performed by central review according to the modified response evaluation criteria in solid tumors (RECIST). Response rate is defined as the percentage of participants with a complete response (CR) or partial response (PR) at the Week 9/10 assessment visit and a corresponding CR or PR confirmed at the Week 13/14 assessment visit for the Q2W/Q3W regimens. CR: Disappearance of all target and non-target lesions and no new lesions. PR: Either the disappearance of all target lesions with persistence of one or more non-target lesion(s) not qualifying for either CR or progressive disease (PD; ≥ 25% increase in lesion size) and no new lesions, or, at least a 30% decrease in the size of target lesions with no progression of existing non-target lesions, and no new lesions.

Outcome measures

Outcome measures
Measure	Pre-emptive Skin Treatment n=48 Participants Participants received either FOLFIRI and panitumumab 6 mg/kg once every 2 weeks (Q2W) or irinotecan and panitumumab 9 mg/kg once every 3 weeks (Q3W), and pre-emptive skin treatment which included skin moisturizer, sunscreen, 1% hydrocortisone cream, and an oral antibiotic for 6 weeks starting 24 hours prior to chemotherapy.	Reactive Skin Treatment n=47 Participants Participants received either FOLFIRI and panitumumab 6 mg/kg Q2W or irinotecan and panitumumab 9 mg/kg Q3W. Participants were treated for each individual skin toxicity occurrence according to prespecified guidelines and based on the type and severity. Treatment could include emollient, sunscreen, topical or oral steroids, antibiotics, or antihistamines, as required.
Response Rate at First Scheduled Assessment	6 percentage of participants Interval 0.0 to 13.0	6 percentage of participants Interval 0.0 to 13.0

SECONDARY outcome

Timeframe: Response was assessed at Weeks 9 and 13 and then every 8 weeks for the Q2W regimen, or at Weeks 10, 14, 22 and then every 9 weeks for the Q3W regimen until the end of treatment; median treatment duration was 13 and 17 weeks in each group respectively.

Population: Primary Analysis Set; participants who prematurely discontinued without a post-baseline tumor assessment or with an observed CR or PR that was not confirmed were considered non-responders.

Best overall response rate is defined as the percentage of participants with a complete response (CR) or partial response (PR) while on study. Tumor response was assessed by CT scan or MRI of the abdomen, pelvis, and all other sites of disease. Disease assessments were performed by central review according to the modified RECIST criteria. CR: Disappearance of all target and non-target lesions and no new lesions. PR: Either the disappearance of all target lesions with persistence of one or more non-target lesion(s) not qualifying for either CR or PD (≥ 25% increase in lesion size) and no new lesions, or, at least a 30% decrease in the size of target lesions with no progression of existing non-target lesions, and no new lesions.

Outcome measures

Outcome measures
Measure	Pre-emptive Skin Treatment n=48 Participants Participants received either FOLFIRI and panitumumab 6 mg/kg once every 2 weeks (Q2W) or irinotecan and panitumumab 9 mg/kg once every 3 weeks (Q3W), and pre-emptive skin treatment which included skin moisturizer, sunscreen, 1% hydrocortisone cream, and an oral antibiotic for 6 weeks starting 24 hours prior to chemotherapy.	Reactive Skin Treatment n=47 Participants Participants received either FOLFIRI and panitumumab 6 mg/kg Q2W or irinotecan and panitumumab 9 mg/kg Q3W. Participants were treated for each individual skin toxicity occurrence according to prespecified guidelines and based on the type and severity. Treatment could include emollient, sunscreen, topical or oral steroids, antibiotics, or antihistamines, as required.
Best Overall Response Rate	15 percentage of participants Interval 5.0 to 25.0	11 percentage of participants Interval 2.0 to 19.0

SECONDARY outcome

Timeframe: Week 9 with confirmed response at Week 13 for the FOLFIRI and panitumumab Q2W regimen or at Week 10 with confirmed response at Week 14 for the irinotecan and panitumumab Q3W regimen.

Population: Primary Analysis Set; participants who prematurely discontinued without a postbaseline tumor assessment or with an observed CR or PR at Week 9 or 10 that was not confirmed at Week 13 or 14 were considered non-responders.

Tumor response was assessed by CT scan or MRI of the abdomen, pelvis, and all other sites of disease. Disease assessments were performed by central review according to the modified response evaluation criteria in solid tumors (RECIST). Disease control rate is defined as the percentage of participants with a CR, PR or stable disease (SD) at the Week 9/10 assessment visit and a corresponding response (CR or PR) confirmed at the Week 13/14 assessment visit for the Q2W/Q3W regimens. SD: Neither sufficient shrinkage or increase in target lesions to qualify for PR or PD, with no progression of non-target lesions and no new lesions.

Outcome measures

Outcome measures
Measure	Pre-emptive Skin Treatment n=48 Participants Participants received either FOLFIRI and panitumumab 6 mg/kg once every 2 weeks (Q2W) or irinotecan and panitumumab 9 mg/kg once every 3 weeks (Q3W), and pre-emptive skin treatment which included skin moisturizer, sunscreen, 1% hydrocortisone cream, and an oral antibiotic for 6 weeks starting 24 hours prior to chemotherapy.	Reactive Skin Treatment n=47 Participants Participants received either FOLFIRI and panitumumab 6 mg/kg Q2W or irinotecan and panitumumab 9 mg/kg Q3W. Participants were treated for each individual skin toxicity occurrence according to prespecified guidelines and based on the type and severity. Treatment could include emollient, sunscreen, topical or oral steroids, antibiotics, or antihistamines, as required.
Rate of Disease Control at First Scheduled Assessment	63 percentage of participants Interval 49.0 to 76.0	64 percentage of participants Interval 50.0 to 78.0

SECONDARY outcome

Timeframe: From randomization until the end of study; median time on study was 31 weeks and 41 weeks in each treatment group respectively with a maximum time on study of 97 weeks.

Population: Primary Analysis Set

Time-to-treatment failure is defined as the time from the date of randomization to the first date of any of the following events: discontinuation of study therapy due to any reason (except for complete response and curative surgery), progression of disease, or death due to any cause. Participants who did not discontinue, who were still alive, and who did not have disease progression were censored at the date of last contact. Time to treatment failure was analyzed using the Kaplan-Meier method.

Outcome measures

Outcome measures
Measure	Pre-emptive Skin Treatment n=48 Participants Participants received either FOLFIRI and panitumumab 6 mg/kg once every 2 weeks (Q2W) or irinotecan and panitumumab 9 mg/kg once every 3 weeks (Q3W), and pre-emptive skin treatment which included skin moisturizer, sunscreen, 1% hydrocortisone cream, and an oral antibiotic for 6 weeks starting 24 hours prior to chemotherapy.	Reactive Skin Treatment n=47 Participants Participants received either FOLFIRI and panitumumab 6 mg/kg Q2W or irinotecan and panitumumab 9 mg/kg Q3W. Participants were treated for each individual skin toxicity occurrence according to prespecified guidelines and based on the type and severity. Treatment could include emollient, sunscreen, topical or oral steroids, antibiotics, or antihistamines, as required.
Time to Treatment Failure	3.1 months Interval 2.3 to 4.8	4.2 months Interval 3.2 to 5.3

SECONDARY outcome

Timeframe: From randomization until the end of study; median time on study was 31 weeks and 41 weeks in each treatment group respectively with a maximum time on study of 97 weeks.

Population: Primary Analysis Set

Time from the date of randomization to the date of observed disease progression or death due to disease progression. Participants who did not have documented disease progression were censored at the date of last tumor assessment; participants who died for reasons other than disease progression while on study were censored at the date of death. PD: At least a 20% increase in the size of target lesions, recorded since the treatment started, or at least a 25% increase in size of non-target lesions and the lesion(s) measure \> 10 mm in one dimension, or the appearance of one or more new lesions. Time to progression was analyzed using the Kaplan-Meier method. This analysis excludes any data collected during follow-up for participants who began third-line treatment.

Outcome measures

Outcome measures
Measure	Pre-emptive Skin Treatment n=48 Participants Participants received either FOLFIRI and panitumumab 6 mg/kg once every 2 weeks (Q2W) or irinotecan and panitumumab 9 mg/kg once every 3 weeks (Q3W), and pre-emptive skin treatment which included skin moisturizer, sunscreen, 1% hydrocortisone cream, and an oral antibiotic for 6 weeks starting 24 hours prior to chemotherapy.	Reactive Skin Treatment n=47 Participants Participants received either FOLFIRI and panitumumab 6 mg/kg Q2W or irinotecan and panitumumab 9 mg/kg Q3W. Participants were treated for each individual skin toxicity occurrence according to prespecified guidelines and based on the type and severity. Treatment could include emollient, sunscreen, topical or oral steroids, antibiotics, or antihistamines, as required.
Time to Progression	4.9 months Interval 3.1 to 6.4	4.1 months Interval 2.9 to 6.2

SECONDARY outcome

Timeframe: From randomization until the end of study; median time on study was 31 weeks and 41 weeks in each treatment group respectively with a maximum time on study of 97 weeks.

Population: Primary Analysis Set

Overall Survival is defined as the time from the date of randomization to the date of death. Participants who did not die while on study or who were lost-to-follow-up were censored at their last contact date. Overall survival was analyzed using all data regardless of whether it was collected during second- or third-line treatment.

Outcome measures

Outcome measures
Measure	Pre-emptive Skin Treatment n=48 Participants Participants received either FOLFIRI and panitumumab 6 mg/kg once every 2 weeks (Q2W) or irinotecan and panitumumab 9 mg/kg once every 3 weeks (Q3W), and pre-emptive skin treatment which included skin moisturizer, sunscreen, 1% hydrocortisone cream, and an oral antibiotic for 6 weeks starting 24 hours prior to chemotherapy.	Reactive Skin Treatment n=47 Participants Participants received either FOLFIRI and panitumumab 6 mg/kg Q2W or irinotecan and panitumumab 9 mg/kg Q3W. Participants were treated for each individual skin toxicity occurrence according to prespecified guidelines and based on the type and severity. Treatment could include emollient, sunscreen, topical or oral steroids, antibiotics, or antihistamines, as required.
Overall Survival	11.2 months Interval 8.3 to 16.1	13.6 months Interval 9.9 to 19.0

SECONDARY outcome

Timeframe: From randomization until the end of study; median time on study was 31 weeks and 41 weeks in each treatment group respectively with a maximum time on study of 97 weeks.

Population: Primary Analysis Set

Defined as the time from the date of randomization to the first date of observed disease progression or death due to any cause (whichever comes first). Participants who were alive and had not progressed while on study were censored at the date of last progression-free tumor assessment.

Outcome measures

Outcome measures
Measure	Pre-emptive Skin Treatment n=48 Participants Participants received either FOLFIRI and panitumumab 6 mg/kg once every 2 weeks (Q2W) or irinotecan and panitumumab 9 mg/kg once every 3 weeks (Q3W), and pre-emptive skin treatment which included skin moisturizer, sunscreen, 1% hydrocortisone cream, and an oral antibiotic for 6 weeks starting 24 hours prior to chemotherapy.	Reactive Skin Treatment n=47 Participants Participants received either FOLFIRI and panitumumab 6 mg/kg Q2W or irinotecan and panitumumab 9 mg/kg Q3W. Participants were treated for each individual skin toxicity occurrence according to prespecified guidelines and based on the type and severity. Treatment could include emollient, sunscreen, topical or oral steroids, antibiotics, or antihistamines, as required.
Progression-free Survival	4.7 months Interval 2.9 to 6.0	4.1 months Interval 2.9 to 6.2

SECONDARY outcome

Timeframe: Baseline and Weeks 2, 3, 4, 5, 6 and 7

Population: Patient Reported Outcomes (PRO) Analysis Set (randomized participants who signed informed consent before protocol-specified procedures, received at least 1 dose of panitumumab, with a non-missing baseline overall DLQI score and who had at least 1 post-baseline non-missing overall DLQI score) with available data at each time point.

Skin-related quality of life was assessed using the DLQI. The DLQI questionnaire asks participants to evaluate the degree that their skin condition has affected their quality of life in the last week. Participants answer 10 questions on a scale from 0 (not at all) to 3 (very much); The DLQI score is calculated by summing the scores for all questions, resulting in a maximum of 30 and a minimum of 0; higher scores indicate a more impaired quality of life.

Outcome measures

Outcome measures
Measure	Pre-emptive Skin Treatment n=46 Participants Participants received either FOLFIRI and panitumumab 6 mg/kg once every 2 weeks (Q2W) or irinotecan and panitumumab 9 mg/kg once every 3 weeks (Q3W), and pre-emptive skin treatment which included skin moisturizer, sunscreen, 1% hydrocortisone cream, and an oral antibiotic for 6 weeks starting 24 hours prior to chemotherapy.	Reactive Skin Treatment n=44 Participants Participants received either FOLFIRI and panitumumab 6 mg/kg Q2W or irinotecan and panitumumab 9 mg/kg Q3W. Participants were treated for each individual skin toxicity occurrence according to prespecified guidelines and based on the type and severity. Treatment could include emollient, sunscreen, topical or oral steroids, antibiotics, or antihistamines, as required.
Change From Baseline in Overall Dermatologic Quality of Life Index (DLQI) Score Change from Baseline to Week 7 (n=40, 40)	2.0 units on a scale Standard Deviation 2.8	2.6 units on a scale Standard Deviation 4.4
Change From Baseline in Overall Dermatologic Quality of Life Index (DLQI) Score Baseline (n=46, 44)	0.3 units on a scale Standard Deviation 0.7	0.1 units on a scale Standard Deviation 0.3
Change From Baseline in Overall Dermatologic Quality of Life Index (DLQI) Score Change from Baseline to Week 2 (n=42, 41)	0.7 units on a scale Standard Deviation 1.4	1.6 units on a scale Standard Deviation 3.7
Change From Baseline in Overall Dermatologic Quality of Life Index (DLQI) Score Change from Baseline to Week 3 (n=44, 42)	1.3 units on a scale Standard Deviation 2.6	4.2 units on a scale Standard Deviation 5.8
Change From Baseline in Overall Dermatologic Quality of Life Index (DLQI) Score Change from Baseline to Week 4 (n=42, 42)	1.7 units on a scale Standard Deviation 2.4	3.8 units on a scale Standard Deviation 5.4
Change From Baseline in Overall Dermatologic Quality of Life Index (DLQI) Score Change from Baseline to Week 5 (n=44, 42)	1.3 units on a scale Standard Deviation 2.3	2.7 units on a scale Standard Deviation 4.2
Change From Baseline in Overall Dermatologic Quality of Life Index (DLQI) Score Change from Baseline to Week 6 (n=42, 38)	1.6 units on a scale Standard Deviation 2.8	2.3 units on a scale Standard Deviation 3.9

Adverse Events

Pre-emptive Skin Treatment

Serious events: 13 serious events

Other events: 47 other events

Deaths: 0 deaths

Reactive Skin Treatment

Serious events: 23 serious events

Other events: 47 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Study Director

Amgen Inc.

Phone: 866-572-6436

Results disclosure agreements

Principal investigator is a sponsor employee The Clinical Trial Agreement generally does not restrict an investigator's discussion of trial results after completion. The Agreement permits Amgen a limited period of time to review material discussing trial results (typically up to 45 days and possible extension). Amgen may remove confidential information, but authors have final control and approval of publication content. For multicenter studies, the investigator agrees not to publish any results before the first multi-center publication.
Publication restrictions are in place

Restriction type: OTHER