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Eric Van Cutsem, 1

Rash as a marker for the efficacy of gemcitabine plus erlotinib-based therapy in pancreatic cancer: results from the AViTA study. Eric Van Cutsem, 1 Walter Vervenne, 2 Jaafar Bennouna, 3 Yves Humblet, 4 Chris Verslype 1 and Jan Cosaert 5

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Eric Van Cutsem, 1

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  1. Rash as a marker for the efficacy of gemcitabine plus erlotinib-based therapy in pancreatic cancer: results from the AViTA study Eric Van Cutsem,1 Walter Vervenne,2 Jaafar Bennouna,3 Yves Humblet,4 Chris Verslype1 and Jan Cosaert5 1University Hospital Gasthuisberg, Leuven, Belgium; 2Deventer Hospital, Deventer, The Netherlands; 3Centre René Gauducheau, Saint Herblain, France 4Centre du Cancer, Université Catholique de Louvain, Brussels, Belgium, 5F. Hoffmann-La Roche, Basel, Switzerland

  2. PA.3: significant improvement in OS with addition of erlotinib to gemcitabine 1.00 0.75 0.50 0.25 0 Survival probability HR=0.82 (95% CI: 0.69–0.99) p=0.038 0 6 12 18 24 30 36 Time (months) OS = overall survivalG = gemcitabine; E = erlotinib; P = placebo Moore M, et al. J Clin Oncol 2007;25:1960–6

  3. PA.3: OS relative to grade of rash 1.0 0.8 0.6 0.4 0.2 0 Survival probability Grade 0 Grade 1 Grade 2 p<0.0001 HR (rash)=0.71 0 5 10 15 20 Time (months) Moore M, et al. J Clin Oncol 2007;25:1960–6; Roche, data on file

  4. AViTA: study design • Stratified according to country, KPS (<80% vs ≥80%), albumin level (<2.9g/dL vs ≥2.9g/dL) R A N D O M I Z A T I O N GE-B (n=306) PD Previously untreated metastatic pancreatic cancer 1:1 GE-P(n=301) PD G: 1,000mg/m2 on days 1, 8, 15, 22, 29, 36, 43 for first 8 weeks, days 1, 8, 15 in subsequent 4-week cycles; E 100mg/day; B 5mg/kg q2w B = bevacizumab KPS = Karnofsky performance statusPD = progressive disease Vervenne W, Van Cutsem E, et al. J Clin Oncol 2008;26(Suppl.):214s (Abs. 4507) Van Cutsem E et al, accepted J Clin Oncol 2009

  5. AViTA objectives and inclusion/exclusion criteria • Primary endpoint: • OS • Secondary endpoints: • Progression-free survival (PFS), response rate, and safety (adverse events [AEs] graded by NCI-CTC v3.0) • Exploratory analysis • OS, PFS, and disease control rate according to occurrence and grade of rash • Inclusion criteria • histologically confirmed, metastatic pancreatic adenocarcinoma; no prior therapy for metastatic disease; >6 months since adjuvant therapy; no prior gemcitabine or anti-vascular endothelial growth factor (VEGF) therapy; KPS ≥60; adequate hematologic, hepatic, and renal function • Exclusion criteria • invasion of major blood vessels; surgery in last 28 days; bleeding disorders; significant cardiovascular disease

  6. OS and PFS in AViTA OS PFS 1.0 0.8 0.6 0.4 0.2 0 1.0 0.8 0.6 0.4 0.2 0 GE-B (n=221 with events) GE-P(n=233 with events) GE-B (n=257 with events) GE-P(n=278 with events) p=0.2087HR=0.89 (95% CI: 0.74–1.07) p=0.0002 HR=0.73 (95% CI: 0.61–0.86) PFS probability OS probability 6.0 7.1 3.6 4.6 0 3 6 9 12 15 18 21 24 0 3 6 9 12 15 18 21 24 Time (months) Time (months) Vervenne W, Van Cutsem E, et al. J Clin Oncol 2008;26(Suppl.):214s (Abs. 4507)

  7. Incidence of AEs in both treatment arms aOne patient in the placebo arm had a grade 5 event

  8. Baseline characteristics by grade of rash

  9. 1.0 0.8 0.6 0.4 0.2 0 1.0 0.8 0.6 0.4 0.2 0 1.0 0.8 0.6 0.4 0.2 0 GE-B grade 0 GE-B grade  1 GE-P grade 0 GE-P grade  1 All grade 0 All grade 1 All grade 2 All grade 0 All grade 1 OS OS OS p<0.0001 HR=0.54 (95% CI: 0.44–0.65) 0 6 12 18 24 0 6 12 18 24 0 6 12 18 24 Time (months) Time (months) Time (months) No. left GE-B gr 0 GE-B gr 1 GE-P gr 0 GE-P gr 1 No. left All gr 0 214 78 12 1 0 All gr 1 393 240 46 2 0 No. left All gr 0 214 78 12 1 0All gr 1 211 121 20 0 0 All gr 2 182 119 26 2 0 91 37 3 0 0 215 137 25 1 0 123 41 9 1 0 178 103 21 1 0 OS relative to rash

  10. OS according to severity of rash N.B. All hazard ratios (HRs) are for rash versus no rash

  11. 1.0 0.8 0.6 0.4 0.2 0 1.0 0.8 0.6 0.4 0.2 0 1.0 0.8 0.6 0.4 0.2 0 GE-B grade 0 GE-B grade  1 GE-P grade 0 GE-P grade  1 All grade 0 All grade 1 All grade 2 All grade 0 All grade 1 PFS PFS PFS p<0.0001 HR=0.53 (95% CI: 0.44–0.63) 0 6 12 18 24 0 6 12 18 24 0 6 12 18 24 Time (months) Time (months) Time (months) No. left All gr 0 214 36 0 0 0All gr 1 211 54 6 0 0 All gr 2 393 122 15 1 0 No. left All gr 0 214 36 0 0 0All gr 1 393 122 15 1 0 No. left GE-B gr 0 91 21 0 0 0 GE-B gr 1 215 77 10 1 0 GE-P gr 0 123 15 0 0 0 GE-P gr 1 178 45 5 0 0 PFS relative to rash

  12. PFS according to severity of rash N.B. All HRs are for rash versus no rash

  13. Conclusions • Rash was associated with improved outcomes for erlotinib-based therapy in AViTA, confirming the results seen in PA.3 • this was a retrospective exploratory analysis not corrected for multiple testing • This association was consistent across treatment arms and endpoints • benefit was seen for all grades of rash, not just severe rash • Some baseline characteristics appear to be associated with an increased incidence of rash and improved efficacy; this warrants further prospective investigation

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