American Society of Clinical Oncology 2009 Final STEPP results of prophylactic versus reactive skin...

American Society of Clinical Oncology 2009

Final STEPP results of prophylactic versus reactive Final STEPP results of prophylactic versus reactive skin toxicity (ST) treatment (tx) for panitumumab skin toxicity (ST) treatment (tx) for panitumumab

(pmab)-related ST in patients (pts) with metastatic (pmab)-related ST in patients (pts) with metastatic colorectal cancer (mCRC)colorectal cancer (mCRC)

Edith P. Mitchell,Edith P. Mitchell,11 Mario Lacouture, Mario Lacouture,22 Heather Heather Shearer,Shearer,33 Nicholas Iannotti, Nicholas Iannotti,44 Bilal Piperdi, Bilal Piperdi,55

Madhavan Pillai,Madhavan Pillai,66 Feng Xu, Feng Xu,77 Mohamed Yassine Mohamed Yassine77

11Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA;Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA; 22Northwestern University, Chicago, IL;Northwestern University, Chicago, IL;

33Piedmont Hematology Oncology Associates PLLC, Winston-Salem, NC; Piedmont Hematology Oncology Associates PLLC, Winston-Salem, NC; 44Hematology Oncology Associates of Treasure Coast, Port Saint Lucie, FL; Hematology Oncology Associates of Treasure Coast, Port Saint Lucie, FL;

55University ofUniversity of Massachusetts Medical Center, Worcester, MA; Massachusetts Medical Center, Worcester, MA; 66Virginia Oncology Care PC, Richlands, VA;Virginia Oncology Care PC, Richlands, VA;

77Amgen Inc., Thousand Oaks, CAAmgen Inc., Thousand Oaks, CA


IntroductionIntroduction• Colorectal cancer is the third most common cancer worldwide, with approximatelyColorectal cancer is the third most common cancer worldwide, with approximately

1 million new cases diagnosed annually1 million new cases diagnosed annually11

• Panitumumab, a fully human monoclonal antibody targeting the epidermal growth Panitumumab, a fully human monoclonal antibody targeting the epidermal growth factor receptor (EGFR), is approved in thefactor receptor (EGFR), is approved in the US as monotherapy for US as monotherapy for mCRC after mCRC after disease progression on standard chemotherapy and in the EU and Canada as disease progression on standard chemotherapy and in the EU and Canada as monotherapy in patients with wild-type monotherapy in patients with wild-type KRASKRAS tumor status tumor status2,32,3

• Skin toxicities are the most common treatment‑related side effects of anti‑EGFR Skin toxicities are the most common treatment‑related side effects of anti‑EGFR therapytherapy3,43,4

• The STEPP study is the first prospective study to examine differences between The STEPP study is the first prospective study to examine differences between prophylactic and reactive skin treatment for skin toxicities associated with any prophylactic and reactive skin treatment for skin toxicities associated with any EGFR inhibitorEGFR inhibitor

• This is the final analysis of STEPP on safety and efficacy of panitumumab by skin This is the final analysis of STEPP on safety and efficacy of panitumumab by skin treatment and treatment and KRASKRAS status status


Study ObjectivesStudy Objectives• To estimate the difference in the incidence of specific ≥ To estimate the difference in the incidence of specific ≥

grade 2 skin toxicities of interest between patients grade 2 skin toxicities of interest between patients receiving prophylactic or reactive skin treatment arms receiving prophylactic or reactive skin treatment arms during the 6-week skin treatment periodduring the 6-week skin treatment period

• Secondary objectives:Secondary objectives:

– Assessments of other skin toxicity events during the Assessments of other skin toxicity events during the 6-week skin treatment period6-week skin treatment period

– Safety and efficacy of panitumumab plus irinotecan-Safety and efficacy of panitumumab plus irinotecan-based chemotherapy by based chemotherapy by KRASKRAS status status


Methods: Study DesignMethods: Study Design• Phase 2, multicenter, open-label, randomized clinical trial conducted in the USPhase 2, multicenter, open-label, randomized clinical trial conducted in the US

• Patients received either pmab 6 mg/kg/FOLFIRI Q2W or pmab 9.0 mg/kg/ irinotecan Patients received either pmab 6 mg/kg/FOLFIRI Q2W or pmab 9.0 mg/kg/ irinotecan chemotherapy Q3W by investigators choicechemotherapy Q3W by investigators choice

• Tumor response was assessed byTumor response was assessed by central review using modified Response Evaluation central review using modified Response Evaluation Criteria in Solid Tumors (RECIST) at weeks 9 and 13, and Q8W thereafter for patients on the Criteria in Solid Tumors (RECIST) at weeks 9 and 13, and Q8W thereafter for patients on the Q2W regimen, and at weeks 10, 14, 22, and then Q9W thereafter for patients on the Q3W Q2W regimen, and at weeks 10, 14, 22, and then Q9W thereafter for patients on the Q3W regimenregimen

• Within each chemotherapy stratum, patients were randomized in a 1:1 ratio to either the Within each chemotherapy stratum, patients were randomized in a 1:1 ratio to either the prophylactic or reactive skin treatmentprophylactic or reactive skin treatment

• Patient-reported Quality of Life was assessed using the Dermatology Life Quality Index Patient-reported Quality of Life was assessed using the Dermatology Life Quality Index (DLQI) at screening during weeks 2 to 7, and at the week 13 or 14 visit, depending on (DLQI) at screening during weeks 2 to 7, and at the week 13 or 14 visit, depending on treatment scheduletreatment schedule

• Patients continued on-study until completion of the post-treatment follow-up period, death, Patients continued on-study until completion of the post-treatment follow-up period, death, withdrawal of full consent, or lost to follow-upwithdrawal of full consent, or lost to follow-up


STEPP Study SchemaSTEPP Study Schema

Prophylactic SkinProphylactic Skin

TreatmentTreatment

SSCCRREEEEN N I I NNGG

RRAANNDDOOMMI I ZZAAT T I I OONN

PPRROOGGRREESSS S IIOONN

OOVVEER R AAL L LL

SSUURRVVIIVVAALL

FFOOLLLLOOWW

UUPP

SSAAFFEETTYY

FFOOLLLLOOWW

UUPP

SSKKIINN

TTOOXXIICCIITTY Y

EEVVAALLUUAATTIIOONNbb

TTUUMMOORR

RREESSPPOONNSSEE

EEVVAALLUUAATTIIOONN

Q8WQ8W or Q9W or Q9W

n = n = 9595

n = 48n = 48

n = 47n = 47

Reactive SkinReactive Skin

TreatmentTreatment

1:11:1aa

aaStratified by chemotherapy regimen (investigator choice): either FOLFIRI and Stratified by chemotherapy regimen (investigator choice): either FOLFIRI and panitumumab Q2W regimen or irinotecan and panitumumab Q3W regimenpanitumumab Q2W regimen or irinotecan and panitumumab Q3W regimenbbSkin treatment period: Weeks 1 to 6 (start day - 1)Skin treatment period: Weeks 1 to 6 (start day - 1) Skin assessment period: QW from weeks 1 to 7Skin assessment period: QW from weeks 1 to 7


Skin TreatmentSkin Treatment

• Prophylactic skin treatment regimen administered weeks 1 to 6 Prophylactic skin treatment regimen administered weeks 1 to 6 (beginning day 1):(beginning day 1):

• Skin moisturizer – apply to face, hands, feet, neck, back, and Skin moisturizer – apply to face, hands, feet, neck, back, and chest daily in the morning upon risingchest daily in the morning upon rising

• Sunscreen (PABA free, SPF ≥ 15, UVA/UVB protection) – Sunscreen (PABA free, SPF ≥ 15, UVA/UVB protection) – apply to exposed skin areas before going outdoorsapply to exposed skin areas before going outdoors

• Topical steroid (1% hydrocortisone cream) – apply to face, Topical steroid (1% hydrocortisone cream) – apply to face, hands, feet, neck, back, and chest at bedtime hands, feet, neck, back, and chest at bedtime

• Doxycycline 100 mg BIDDoxycycline 100 mg BID• Per investigator discretion, aPer investigator discretion, a reactive skin treatment was reactive skin treatment was

administered anytime during weeks 1-6 administered anytime during weeks 1-6 • From week 7 and thereafter, investigators had the option to From week 7 and thereafter, investigators had the option to

continue patients on the assigned skin treatment regimencontinue patients on the assigned skin treatment regimen


Key Eligibility CriteriaKey Eligibility Criteria• ≥ ≥ 18 years of age18 years of age• Unresectable metastatic adenocarcinoma of the colon or rectum Unresectable metastatic adenocarcinoma of the colon or rectum

that cannot, per investigator, be cured by surgical resection at the that cannot, per investigator, be cured by surgical resection at the time of randomizationtime of randomization

• Measurable disease per modified RECISTMeasurable disease per modified RECIST• Failure of first-line treatment containing fluoropyrimidine and Failure of first-line treatment containing fluoropyrimidine and

oxaliplatin-based chemotherapy with or without bevacizumab for oxaliplatin-based chemotherapy with or without bevacizumab for mCRCmCRC– Treatment failure was defined as progression of disease or Treatment failure was defined as progression of disease or

toxicity-based from fluoropyrimidine, oxaliplatin, and/or toxicity-based from fluoropyrimidine, oxaliplatin, and/or bevacizumabbevacizumab

• ECOG performance status of 0 or 1ECOG performance status of 0 or 1• No prior irinotecan use for the treatment of mCRCNo prior irinotecan use for the treatment of mCRC


Statistical AnalysisStatistical Analysis• This is the final analysis of the STEPP studyThis is the final analysis of the STEPP study

• Skin toxicity, anti-tumor efficacy, and safety endpoints were analyzed Skin toxicity, anti-tumor efficacy, and safety endpoints were analyzed on the primary analysis set including all randomized patientson the primary analysis set including all randomized patients

• Analyses by Analyses by KRASKRAS were defined as a subset of patients with evaluable were defined as a subset of patients with evaluable KRASKRAS status status

• Quality of life data were based on PRO analysis set defined as a subset Quality of life data were based on PRO analysis set defined as a subset of patients with baseline and at least one post-baseline PRO resultsof patients with baseline and at least one post-baseline PRO results

• Logistic regression model was employed to estimate the treatment Logistic regression model was employed to estimate the treatment effect on the binary endpoints of interest. The Odds Ratio (OR) and effect on the binary endpoints of interest. The Odds Ratio (OR) and 95% CI using the Wald method were provided 95% CI using the Wald method were provided

• AEs (adverse events) were grouped by using MedDRA 9.0. The severity AEs (adverse events) were grouped by using MedDRA 9.0. The severity of AEs was coded according to the NCI CTCAE v. 3.0 with modification of AEs was coded according to the NCI CTCAE v. 3.0 with modification for Dermatology Toxicity Grading for skin related toxicitiesfor Dermatology Toxicity Grading for skin related toxicities


Table 1: Patient DispositionTable 1: Patient Disposition

Prophylactic Prophylactic Skin TreatmentSkin Treatment

N = 48N = 48

Reactive Skin Reactive Skin TreatmentTreatment

N = 47N = 47

Patients who ended second-line treatment – n (%)Patients who ended second-line treatment – n (%) 48 (100)48 (100) 47 (100)47 (100)

Reason for ending treatment – n (%)Reason for ending treatment – n (%)

Disease progressionDisease progression 30 (63)30 (63) 28 (60)28 (60)

Adverse eventAdverse event 5 (10)5 (10) 5 (11)5 (11)

Patient requestPatient request 5 (10)5 (10) 6 (13)6 (13)

DeathDeath 3 (6)3 (6) 2 (4)2 (4)

OtherOther 5 (10)5 (10) 6 (13)6 (13)

Median follow-up timeMedian follow-up time11, weeks, weeks 31.031.0 40.740.71 1 Follow-up time is calculated as the randomization date to the last on-study or long-term follow-up visit.Follow-up time is calculated as the randomization date to the last on-study or long-term follow-up visit.


Prophylactic Skin TreatmentProphylactic Skin TreatmentN = 48N = 48

Reactive Skin TreatmentReactive Skin TreatmentN = 47N = 47

Sex – n (%)Sex – n (%)

MenMen 32 (67)32 (67) 26 (55)26 (55)

Race – n (%)Race – n (%)

White or CaucasianWhite or Caucasian 34 (71)34 (71) 40 (85)40 (85)

Black or African AmericanBlack or African American 6 (13)6 (13) 5 (11)5 (11)

Hispanic or LatinoHispanic or Latino 5 (10)5 (10) 1 (2)1 (2)

OtherOther 3 (6)3 (6) 1 (2)1 (2)

Age – years, median (min, max)Age – years, median (min, max) 60 (24, 84)60 (24, 84) 61 (40, 86)61 (40, 86)

ECOG performance status – n (%)ECOG performance status – n (%)

00 34 (71)34 (71) 30 (64)30 (64)

11 12 (25)12 (25) 17 (36)17 (36)

22 2 (4)2 (4) 0 (0)0 (0)

Primary tumor type – n (%)Primary tumor type – n (%)

ColonColon 34 (71)34 (71) 28 (60)28 (60)

RectalRectal 14 (29)14 (29) 19 (40)19 (40)

Number of metastatic sites – n (%)Number of metastatic sites – n (%)

11 18 (38)18 (38) 17 (36)17 (36)

> 1> 1 30 (63)30 (63) 30 (64)30 (64)

Table 1: Demographics and Disease Characteristics Table 1: Demographics and Disease Characteristics (cont’d)(cont’d)


Primary Endpoint - Incidence of Grade 2 or Higher Skin Primary Endpoint - Incidence of Grade 2 or Higher Skin ToxicitiesToxicities11 in Prophylactic vs Reactive Skin Treatment Arms in Prophylactic vs Reactive Skin Treatment Arms

(During the Skin Treatment Period, Final Analysis)(During the Skin Treatment Period, Final Analysis)

Prophylactic Prophylactic SkinSkin

TreatmentTreatmentN = 48N = 48

Reactive Reactive SkinSkin

TreatmentTreatmentN = 47N = 47

Patients with grade 2 or higher skin toxicity – n (%)Patients with grade 2 or higher skin toxicity – n (%)2 2 14 (29)14 (29) 29 (62)29 (62)

Odds RatioOdds Ratio33 (95% CL) (95% CL) 0.3 (0.1, 0.6) 0.3 (0.1, 0.6)

Grade 2 – n (%)Grade 2 – n (%) 11 (23)11 (23) 19 (40)19 (40)

Grade 3 – n (%)Grade 3 – n (%) 3 (6)3 (6) 10 (21)10 (21)

1 Specific skin toxicities of interest per protocol2 There were no grade 4 skin toxicities during the skin treatment period3 Odds ratio is estimated from a logistic regression model including treatment (prophylactic vs reactive) that includes an

adjustment for chemotherapy stratum (Q2W vs Q3W)


Probability of Grade 2 or Higher Skin ToxicityProbability of Grade 2 or Higher Skin Toxicity11 by Time on the by Time on the StudyStudy

1Specific skin toxicities of interest per protocol

Weeks

Prophylactic N

Events Median (95% CL)n (%) Weeks

Prophylactic 14 (29) NRReactive 29 (62) 2.1 (2.1, 6.3)

Censored480

441

361

275

027

Reactive NCensored

470

362

181

160

015

Su

rviv

al D

istr

ibu

tio

n F

un

ctio

n

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

0 2 4 6 8


Best Overall ResponseBest Overall Response11 and Progression-free and Progression-free Survival By Skin Treatment GroupSurvival By Skin Treatment Group

Central ReviewCentral Review

ProphylacticProphylacticN = 48N = 48

ReactiveReactiveN = 47N = 47

Best overall response – n (%)Best overall response – n (%) 7 (15)7 (15) 5 (11)5 (11)

Complete responseComplete response 0 (0)0 (0) 0 (0)0 (0)

Partial responsePartial response 7 (15)7 (15) 5 (11)5 (11)

Stable diseaseStable disease 24 (50)24 (50) 25 (53)25 (53)

Disease controlDisease control 31 (65)31 (65) 30 (64)30 (64)


Not done or unevaluableNot done or unevaluable 8 (17)8 (17) 7 (15)7 (15)

Progression free survival – KM Progression free survival – KM Median (95% CI) Months Median (95% CI) Months 4.7 (2.9 - 6.0)4.7 (2.9 - 6.0) 4.1 (2.9 - 6.2)4.1 (2.9 - 6.2)

1By independent central review and confirmed by a follow-up assessment no less than 28 days after the criteria for response were first met


Disposition: Disposition: KRASKRAS subsets subsetsPatients enrolled n (%)Patients enrolled n (%) Wild-type Wild-type

KRASKRASN = 49N = 49

Mutant Mutant KRASKRASN = 38N = 38

Total patients ended treatment – n (%)Total patients ended treatment – n (%) 49 (100)49 (100) 38 (100)38 (100)

Reason for ending treatment period – n (%)Reason for ending treatment period – n (%)


DeathDeath 4 (8)4 (8) 0 (0)0 (0)

Protocol deviationProtocol deviation 4 (8)4 (8) 0 (0)0 (0)

Adverse eventsAdverse events 5 (10)5 (10) 5 (13)5 (13)

Patient requestPatient request 8 (16)8 (16) 3 (8)3 (8)

Consent withdrawnConsent withdrawn 0 (0)0 (0) 1 (3)1 (3)

Administrative decisionAdministrative decision 3 (6)3 (6) 1 (3)1 (3)

OtherOther 2 (4)2 (4) 0 (0)0 (0)

Follow-up time (weeks)Follow-up time (weeks)

MedianMedian 39.339.3 33.233.2

RangeRange 0.7, 96.40.7, 96.4 1.7, 96.61.7, 96.6


Best Overall Response by Central review: Best Overall Response by Central review: KRASKRAS subsetssubsets

Wild-typeWild-typeKRASKRASN = 49N = 49

MutantMutantKRASKRASN = 38N = 38

Best overall response – n (%)Best overall response – n (%)aa

Complete responseComplete response 0 (0)0 (0) 0 (0)0 (0)

Partial responsePartial response 8 (16)8 (16) 3 (8)3 (8)

Stable diseaseStable disease 26 (53)26 (53) 21 (55)21 (55)

Disease controlDisease control 34 (69)34 (69) 24 (63)24 (63)


Not done or unevaluableNot done or unevaluable 4 (8)4 (8) 6 (16)6 (16)

aaResponses were confirmed at least 4 weeks after response criteria were first metResponses were confirmed at least 4 weeks after response criteria were first met


Events Events Median (months) Median (months)

N (%) N (%) (95 % CI)(95 % CI) KRASKRAS Wild-type Wild-type 34 (69%)34 (69%) 5.55.5 (4.0 - 6.8)(4.0 - 6.8) KRASKRAS Mutant Mutant 26 (68%)26 (68%) 3.3 (2.9 - 5.2)3.3 (2.9 - 5.2)HR = 0.8 (95% CI: 0.4 - 1.3)HR = 0.8 (95% CI: 0.4 - 1.3)

Central Review of Progression Free Survival by Central Review of Progression Free Survival by KRASKRAS Status: Status:

Months

KRAS Wild Type N 49 32 15 7 1 0Censored 0 2 3 0 2 1

KRAS Mutant N 38 17 6 2 1 0Censored 0 3 1 1 0 0

KRAS Wild TypeKRAS Mutant

Sur

viva

l Dis

trib

utio

n F

unct

ion

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

12840 16 20


Best Overall ResponseBest Overall Response11 and Progression-free Survival by and Progression-free Survival by KRASKRAS Status and Skin Treatment Group Status and Skin Treatment Group22

Central ReviewCentral Review Wild-type Wild-type KRASKRAS Mutant Mutant KRASKRAS

ProphylacticProphylacticN = 23N = 23

ReactiveReactiveN = 26N = 26

ProphylacticProphylactic N = 21N = 21

Reactive Reactive N = 17N = 17

Best overall response – n (%)Best overall response – n (%) 4 (17)4 (17) 4 (15)4 (15) 2 (10)2 (10) 1 (6)1 (6)

Complete responseComplete response 0 (0)0 (0) 0 (0)0 (0) 0 (0)0 (0) 0 (0)0 (0)

Partial responsePartial response 4 (17)4 (17) 4 (15)4 (15) 2 (10)2 (10) 1 (6)1 (6)

Stable diseaseStable disease 13 (57)13 (57) 13 (50)13 (50) 11 (52)11 (52) 10 (59)10 (59)

Disease controlDisease control 17 (74)17 (74) 17 (65)17 (65) 13 (62)13 (62) 11 (65)11 (65)

Disease progressionDisease progression 3 (13)3 (13) 7 (27)7 (27) 5 (24)5 (24) 1 (6)1 (6)

Not done or unevaluableNot done or unevaluable 3 (13)3 (13) 2 (8)2 (8) 3 (14)3 (14) 5 (29)5 (29)

Progression free survival – KM Progression free survival – KM Median (95% CI) Months Median (95% CI) Months 6 (4 - 9)6 (4 - 9) 5 (2 - 8)5 (2 - 8) 3 (3 - 5)3 (3 - 5) 3 (3 - 9)3 (3 - 9)

1Responses were confirmed via central review and confirmed 28 days after the criteria for response was first met2This was an unplanned analysis


NauseaNausea 32 (67)32 (67) 3 (6)3 (6) 0 (0)0 (0) 26 (55)26 (55) 4 (9)4 (9) 0 (0)0 (0)

VomitingVomiting 22 (46)22 (46) 3 (6)3 (6) 0 (0)0 (0) 17 (36)17 (36) 4 (9)4 (9) 0 (0)0 (0)

FatigueFatigue 29 (60)29 (60) 5 (10)5 (10) 0 (0)0 (0) 27 (57)27 (57) 5 (11)5 (11) 0 (0)0 (0)

DiarrheaDiarrhea 27 (56)27 (56) 7 (15)7 (15) 0 (0)0 (0) 40 (85)40 (85) 15 (32)15 (32) 0 (0)0 (0)

NeutropeniaNeutropenia 9 (19)9 (19) 3 (6)3 (6) 1 (2)1 (2) 20 (43)20 (43) 8 (17)8 (17) 4 (9)4 (9)

HypomagnesemiaHypomagnesemia 7 (15)7 (15) 1 (2)1 (2) 1 (2)1 (2) 13 (28)13 (28) 2 (4)2 (4) 1 (2)1 (2)

DehydrationDehydration 6 (13)6 (13) 3 (6)3 (6) 0 (0)0 (0) 16 (34)16 (34) 8 (17)8 (17) 0 (0)0 (0)

Adverse Events of InterestAdverse Events of Interest11 Week 1 Through the Safety Week 1 Through the Safety Follow-upFollow-up

Prophylactic Skin Treatment - N = 48Prophylactic Skin Treatment - N = 48 Reactive Skin Treatment - N = 47Reactive Skin Treatment - N = 47

AnyAnyGradeGrade Grade 3Grade 3 Grade 4Grade 4

AnyAnyGradeGrade Grade 3Grade 3 Grade 4Grade 4

Pts with any event – n (%) Pts with any event – n (%) 48 (100)48 (100) 20 (42)20 (42) 5 (10)5 (10) 47 (100)47 (100) 25 (53)25 (53) 10 (21)10 (21)

Dermatitis acneiformDermatitis acneiform 37 (77)37 (77) 2 (4)2 (4) 0 (0)0 (0) 40 (85)40 (85) 10 (21)10 (21) 0 (0)0 (0)

PruritusPruritus 30 (63)30 (63) 1 (2)1 (2) 0 (0)0 (0) 32 (68)32 (68) 5 (11)5 (11) 0 (0)0 (0)

Pustular rashPustular rash 13 (27)13 (27) 2 (4)2 (4) 0 (0)0 (0) 19 (40)19 (40) 8 (17)8 (17) 0 (0)0 (0)

ParonychiaParonychia 8 (17)8 (17) 0 (0)0 (0) 1 (2)1 (2) 17 (36)17 (36) 3 (6)3 (6) 0 (0)0 (0)

1There were no grade 5 adverse events of interest


Treatment ExposureTreatment Exposure

Prophylactic Skin Treatment Prophylactic Skin Treatment Reactive Skin TreatmentReactive Skin Treatment

Total number of panitumumab dosesTotal number of panitumumab doses11 325325 333333

Total panitumumab doses delayed during Total panitumumab doses delayed during the studythe study11 – n (%) – n (%)

12 (4)12 (4) 21 (6)21 (6)

1Patients who had changes in panitumumab during the study


Dermatologic Toxicities – Grade 3Dermatologic Toxicities – Grade 3

0%0%

5%5%

10%10%

15%15%

20%20%

25%25%

DermatitisDermatitisacneiformacneiform

PruritusPruritus Pustular rashPustular rash ParonychiaParonychia

Prophylactic Skin TreatmentProphylactic Skin Treatment

Reactive Skin TreatmentReactive Skin Treatment

Of these commonly observed dermatologic toxicities, there were no grade 4 Of these commonly observed dermatologic toxicities, there were no grade 4 or 5 events for either skin treatment groupor 5 events for either skin treatment group

% P

atie

nts

% P

atie

nts


Non-Dermatologic Toxicities – Grade 3 and 4Non-Dermatologic Toxicities – Grade 3 and 4

Prophylactic Skin TreatmentProphylactic Skin Treatment

Reactive Skin TreatmentReactive Skin Treatment

Of these commonly observed non-dermatologic toxicities, there were no grade 5 Of these commonly observed non-dermatologic toxicities, there were no grade 5 events for either skin treatment groupevents for either skin treatment group

0%0%5%5%

10%10%15%15%20%20%25%25%30%30%35%35%

NauseaNausea

Gr 3Gr 3

% P

atie

nts

% P

atie

nts

Gr 4Gr 4 Gr 3Gr 3 Gr 4Gr 4 Gr 3Gr 3 Gr 4Gr 4 Gr 3Gr 3 Gr 4Gr 4 Gr 3Gr 3 Gr 4Gr 4 Gr 3Gr 3 Gr 4Gr 4 Gr 3Gr 3 Gr 4Gr 4

VomitingVomiting FatigueFatigue DiarrheaDiarrhea NeutropeniaNeutropenia HypomagnesemiaHypomagnesemia DehydrationDehydration


Prophylactic Prophylactic Skin TreatmentSkin Treatment

N = 46N = 46

Reactive Skin Reactive Skin TreatmentTreatment

N = 44N = 44Mean (SD) DLQI change from baseline to Mean (SD) DLQI change from baseline to week 3 – points week 3 – points 1.3 (2.6) 1.3 (2.6) 4.2 (5.8) 4.2 (5.8)

Mean (SD) DLQI change from baseline to Mean (SD) DLQI change from baseline to week 7 – points week 7 – points 2.0 (2.8) 2.0 (2.8) 2.6 (4.4) 2.6 (4.4)

Mean (SD) DLQI Score Change from Baseline to Week 3 Mean (SD) DLQI Score Change from Baseline to Week 3 and Week 7and Week 711

1Based on the PRO Analysis Set defined as patients who had a baseline and at least 1 post-baseline DLQI score

Patients in the prophylactic skin treatment group reported improved quality of life, especially during weeks 2 to 3 when the median time to first ≥ grade 2 skin toxicityof interest was reached in the reactive skin treatment group


ConclusionsConclusions• The incidence of grade 2 or higher skin toxicities during The incidence of grade 2 or higher skin toxicities during

the 6-week skin treatment period was reduced by more the 6-week skin treatment period was reduced by more than 50% in the prophylactic treatment group compared than 50% in the prophylactic treatment group compared with the reactive treatment groupwith the reactive treatment group

• Numerical differences in favor of the wild-type Numerical differences in favor of the wild-type KRASKRAS group were observed for all efficacy endpoints group were observed for all efficacy endpoints

• Prophylactic and reactive skin treatment regimen had Prophylactic and reactive skin treatment regimen had no difference in efficacy based on skin toxicity regimenno difference in efficacy based on skin toxicity regimen

• A phase 3 registrational study is currently ongoing to A phase 3 registrational study is currently ongoing to investigate panitumumab with FOLFIRI by investigate panitumumab with FOLFIRI by KRASKRAS mutational status in second-line mCRCmutational status in second-line mCRC


ReferencesReferences

1.1. Parkin DM, Bray F, Ferlay J, et al. Global cancer statistics, 2002. Parkin DM, Bray F, Ferlay J, et al. Global cancer statistics, 2002. CA Cancer J CA Cancer J ClinClin. 2005; 55:74-108.. 2005; 55:74-108.

2.2. Jakobovits A, et al. Jakobovits A, et al. Nat Biotech. Nat Biotech. 2007; 25:1134-1143.2007; 25:1134-1143.3.3. VectibixVectibix®® Prescribing Information, Amgen Inc. Thousand Oaks, CA; 2007. Prescribing Information, Amgen Inc. Thousand Oaks, CA; 2007.4.4. Perez-Soler R, Saltz L. Perez-Soler R, Saltz L. J Clin Oncol. 2005;J Clin Oncol. 2005; 23:5235-5246. 23:5235-5246.

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