Presentation on theme: "Waterfall plot analysis of XELOX or XELIRI"— Presentation transcript:
1 Waterfall plot analysis of XELOX or XELIRI with cetuximab or bevacizumabin pts with advanced colorectal cancer (ACRC).Combined analysis of two randomized1st line phase II trials if the AIO CRC study group.Dirk Arnold1, Axel Hinke2, Anke Reinacher-Schick3, Wolff Schmiegel3,Ullrich Graeven4, Stefan Kubicka5, Ludwig Fischer von Weikersthal6,Nicolas Moosmann7, Hans-Joachim Schmoll1, Volker Heinemann71Martin Luther University, Halle; 2WiSP, Langenfeld; 3Ruhr University, Bochum;4Maria Hilf Hospital, Mönchengladbach, 5Medizinische Hochschule, Hannover;6Klinikum St. Marien, Amberg; 7Ludwig Maximilian University, München; all: GermanyWorking Group for Medical Oncology from the German Cancer Society Gastrointestinal Tumor Study Group
2 IntroductionThe Response Evaluation Criteria in Solid Tumors (RECIST) or World Health Organization (WHO) criteria can be used to assess the treatment response rate (RR) in patients with advanced colorectal cancer (ACRC).Owing to the methodology used, RR measures the percentage of patients with relevant tumor shrinkage rather than the magnitude of response or the time until maximal response. Both of these parameters could be relevant for ACRC treatment strategies.Waterfall plots have commonly been used to capture the anti-tumor efficacy of biologic agents that mainly exhibit a cytostatic effect. Thus far, only one waterfall analysis has been conducted to investigate the use of conventional chemotherapy in patients with ACRC.1In order to assess the activity of different compounds used in the treatment of ACRC, waterfall plot analyses were performed on two similarly designed, randomized, first-line, phase II trials:AIO KRK 0104: XELOX-cetuximab vs. XELIRI-cetuximab)(Fischer von Weikersthal et al., ESMO 20062; update ASCO 2008: #4033 )AIO KRK 0604: XELOX-bevacizumab vs. XELIRI-bevacizumab(Schmiegel et al., ASCO 20073; Reinacher-Schick et al., update ASCO 2008: #4030)
3 Method of the analysisUsing RECIST, the percentage change from baseline in tumor volume was evaluated when “best response” to treatment was obtained.A time window of assessment from 6 to 21 weeks (wks) was thereby used throughout the analysis.Average reduction in tumor burden (ARTB)was calculated as difference in waterfall area under curve (AUC) divided by the number of pts., capturing the average reduction in tumor burden.Median reduction in tumor burden (MRTB)captures median tumor size regression from baseline.From the 4 treatment arms, pooled 2x2 analysis was performed to compareXELOX vs. XELIRI(independent from biologic agent)bevacizumab (B) vs. cetuximab (C)(independent from chemotherapy backbone).
4 Patient populationData were available from eligible patients with measurable disease and at least one restaging (taken at “best response”):Pts. (total)Pts. herein% of all pts.AIO KRK 0104:XELOX-cetuximab vs.XELIRI-cetuximab1859293122566669AIO KRK 0604:XELOX-bevacizumab vs.XELIRI-bevacizumab2551271281991009978total44032173
5 Combined analysis - I Best response XELOX arms N=156 XELIRI arms N=165 (compared with baseline)XELOX armsN=156XELIRIarmsN=165BevacizumabN=199CetuximabN=122Tumor growth (% of pts)No Change (% of pts)Tumor shrinkage (% of pts)590678789MRTB (%)33313035ARTB (%)34.7184.108.40.206p (Wilcoxon Mann Whitney Test)0.290.009MRTB = median reduction in tumor burdenARTB = avarage reduction in tumor burden
6 Combined analysis - II102030405060708090100XELOXXELIRIwith Bevacizumabwith CetuximabTm GrowthNo ChangeTm ShrinkageARTB% of pts. (at best response) / % from baseline (ARTB)p=0.29p=0.009Wilcoxon Mann Whitney Test
7 Waterfall plot analysis of the treatment arms CIOX / XELOX + Cetuximab: Best Response100n = 5650AIO 0104:XELOX-cetuximab% change-50-100-150
8 Waterfall plot analysis of the treatment arms CIOX / XELIRI + Cetuximab: Best Response100n = 6650AIO 0104:XELIRI-cetuximab% change-50-100-150
9 Waterfall plot analysis of the treatment arms KRK 0604 / XELOX + Bevacizumab: Best Response100n = 10050AIO 0604:XELOX-bevacizumab% change-50-100-150
10 Waterfall plot analysis of the treatment arms KRK 0604 / XELIRI + Bevacizumab: Best Response100n = 9950AIO 0604:XELIRI-bevacizumab% change-50-100-150
11 ConclusionWaterfall plot analysis was successfully used to evaluate the results ofthe AIO KRK 0104 and the AIO KRK 0604 clinical trials.Waterfall analyses could be used to examine the results of other CRCtrials using chemotherapy and targeted agents.Additional information on the rates of tumor reduction may be obtainedby ARTB and MRTB.Our analysis suggests a larger degree of benefit for cetuximab containingcombinations. However, the results should be interpreted with cautiondue to the limited sample sizes and the retrospective and unpreplannedcharacter of the analysis.ARTB and MRTB should be validated in future trials and in relation toparameters like secondary metastasis resection, but also to clinicallyproven time-to-event-endpoints, like progression free survival and overallsurvival.