Michael Stahlon behalf of the

German Oesophageal Cancer Study Group

Long term results of a phase III study investigating chemoradiation with and

without surgery in locally advanced squamous cell carcinoma of the

esophagus

Abstract No 4530, Poster No 18

Participating CentersParticipating CentersGerman Oesophageal Cancer Study GroupGerman Oesophageal Cancer Study Group

Essen (KEM, AKK, University, EKK)Essen (KEM, AKK, University, EKK)Düsseldorf (University)Düsseldorf (University)Tübingen (University)Tübingen (University)Marburg (University)Marburg (University)Duisburg (St.J., Städt.)Duisburg (St.J., Städt.)Trier (KB)Trier (KB)Berlin (RRK)Berlin (RRK)Göttingen (University)Göttingen (University)Mönchengladbach (Franz.)Mönchengladbach (Franz.)

Eligibility CriteriaEligibility Criteria

SCC of the intrathoracic SCC of the intrathoracic esophagusesophagusStage T3-4 N0-1 M0 according Stage T3-4 N0-1 M0 according to CT und EUSto CT und EUSMedically fit for surgery, PS 0-1Medically fit for surgery, PS 0-1Age up to 70 yearsAge up to 70 yearsWritten informed consentWritten informed consent

Flow Diagram of Patients Flow Diagram of Patients includedincludedAssessed

for eligibilityn = 189

Randomisedn = 172

Refusedrandomisation

n = 12

Excluded(not meeting

inclusion criteria)n = 5

Allocated toArm An = 86

Allocated toArm Bn = 86

Treated An = 7

Treated Bn = 5

Treated n = 86 Treated n = 85

Stahl M, et alJCO 23:2310-7,2005

Stratification CriteriaStratification Criteria

CenterCenterGenderGenderWeight loss (up to vs. above Weight loss (up to vs. above 10% of BW)10% of BW)Complete EUSComplete EUSStage (T3N0 vs. T3N+ vs. T4)Stage (T3N0 vs. T3N+ vs. T4)

EndpointsEndpoints

Primary endpointPrimary endpoint- Overall survivalOverall survival

Secondary endpointsSecondary endpoints- Rate of R0-ResectionRate of R0-Resection- Rate of PCRRate of PCR- Postoperative MortalityPostoperative Mortality- Local tumor controlLocal tumor control

POETGOeCSG

Statistical designStatistical design

Test for equivalence between arms ITest for equivalence between arms I<15%I <15%I

- H0: 35% 2y-survival in Arm A; >20% Arm B- H0: 35% 2y-survival in Arm A; >20% Arm B

N= 175 , power of 80%, N= 175 , power of 80%, =0.05 =0.05

Results at SurgeryResults at Surgery

SurgerySurgery 62 patients62 patientsResectionResection 55 / 62 (89%)55 / 62 (89%)R0R0 51 / 62 (82%)51 / 62 (82%)

ypT0 N0 M0ypT0 N0 M0 18 / 51 (35%)18 / 51 (35%)ypT1-3 N0 M0ypT1-3 N0 M0 17 / 51 (33%)17 / 51 (33%)ypT1-3 N1 M0ypT1-3 N1 M0 9 / 51 (18%) 9 / 51 (18%)ypT1-3 N0-1 M1ypT1-3 N0-1 M1 7 / 51 (14%) 7 / 51 (14%)

Surgical ProceduresSurgical Procedures

ExplorationExploration 7 /62 7 /62ResectionResection 55/62 (89%)55/62 (89%)

TTETTE 49/55 (89%)49/55 (89%)THETHE 4/55 4/55OtherOther 1/55 1/55UnknownUnknown 1/55 1/55

Treatment Related MortalityTreatment Related Mortality

CTXCTX CRTX CRTX Surgery Surgery

Arm AArm A 2/86(2.2%) 2/86(2.2%) 0 0 7/57(12.3%) 7/57(12.3%) Arm BArm B 2/85(2.3%) 2/85(2.3%) 0 0 0/5 0/5 allall 4/171(2.3%) 4/171(2.3%) 0 0 7/62(11.3%) 7/62(11.3%)

Overall 8.2%, including 3 pts. with late toxicity

Patterns of FailurePatterns of Failure (treatment according to protocol)(treatment according to protocol)

Arm A*Arm A* Arm B*Arm B*

Any failureAny failure 31/56 (55%)31/56 (55%) 57/83 (69%)57/83 (69%)

Local+regional 14/31 (45%)Local+regional 14/31 (45%) 41/57 (72%)41/57 (72%)Distant (only)Distant (only) 16/31 (52%)16/31 (52%) 14/57 (25%)14/57 (25%)UnknownUnknown 1/31 ( 3%) 1/31 ( 3%) 2/57 ( 3%) 2/57 ( 3%)

* Arm A: CRTX (at least 36 Gy) + Resection, Arm B: CRTX (at least 59 Gy)

Overall Survival (JCO 2005)Overall Survival (JCO 2005)

Log-rank for equivalenceLog-rank for equivalencep = 0.04p = 0.04

2-YSR38.8% vs. 35.4%

Overall Survival (December 2007)Overall Survival (December 2007)

5-YSR27.9% vs. 17.0%Calculated 10-YSR19.2% vs 12.2%Logrank p=0.36HR 1.15 (0.82-1.61)

- CRTX with Surgery- CRTX alone

Survival as treated (no crossover)Survival as treated (no crossover)

5-YSR28.0% vs. 17.0%Calculated 10-YSR19.8% vs 12.9%Logrank p=0.48HR 1.13 (0.79-1.61)

Cox Regression AnalysisCox Regression Analysis

Progn. FactorProgn. Factor HR HR (95%CI)(95%CI) p-value p-value

CTX-Response (y/n)CTX-Response (y/n) 0.300.30 0.19-0.480.19-0.48 <0.0001 <0.0001

Treatment group (A/B)Treatment group (A/B) 1.191.19 0.80-1.760.80-1.76 0.390.39

Gender (m/f)Gender (m/f) 1.061.06 0.65-1.730.65-1.73 0.820.82

EUS complete (y/n)EUS complete (y/n) 0.910.91 0.61-1.350.61-1.35 0.640.64

Weight loss (</>10%)Weight loss (</>10%) 1.191.19 0.76-1.850.76-1.85 0.450.45

Stage (T3N1/T3N0)Stage (T3N1/T3N0) 1.021.02 0.61-1.700.61-1.70 0.940.94

StageStage (T4NX/T3N0)(T4NX/T3N0)1.011.01 0.52-1.970.52-1.97 0.970.97