ECCLU 2011 - K. Fizazi - Testicular cancer - Treatment of advanced testicular cancer
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1. Advanced testicular cancer has a variable prognosis depending on factors like tumor markers and site of metastases. First-line chemotherapy typically consists of bleomycin, etoposide, and cisplatin (BEP). 2. For good prognosis metastatic seminoma or non-seminoma, 3 cycles of BEP is usually sufficient. For poor prognosis, 4 cycles of BEP is standard despite trials finding no benefit to more treatment. 3. For relapsed or refractory disease, salvage regimens including ifosfamide and cisplatin offer around 25% chance of cure, with prognostic factors predicting outcome. Intensive approaches show no clear benefit.
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ECCLU 2011 - K. Fizazi - Testicular cancer - Treatment of advanced testicular cancer
- 1. Systemic treatment of advanced testicular cancer Karim Fizazi, MD, PhD Institut Gustave Roussy, France
- 2. Metastatic GCT: Prognosis (IGCCC) Good prognosis Intermediate prognosis Poor prognosis J Clin Oncol 1997, 15: 594-603
- 7. Séminomes métastatiques Bon pronostic Pronostic intermédiaire Pas de M+ visc extra-P LDH < 2N si supra-diaph M+ viscérales extra-P ou LDH > 2N si supra-diaph 4 EP 4 VIP + G-CSF IGCCCG MRC
- 9. Survival according to prognosis Progression-free survival (3-year): Good prognosis group: 93% (85-97) Intermediate prognosis group: 83% (63-93) Overall survival (3-year): Good prognosis group: 99% (92-100) Intermediate prognosis group: 87% (67-95) Fizazi K et al., ASCO 2009
- 13. Proposition étude française Séminome stade II (A-C?) 2 cycles d’EP Pet-scan Si - 1 cycle carbo Si + 2 cycles EP
- 14. Treatment for metastatic non-seminomatous germ-cell tumors (NSGCT)
- 19. Logrank p=0.06 n= 251 Good-risk NSGCT Event-Free Survival GETUG T93 trial: 3 BEP vs 4 EP Culine et al., Ann Oncol 2007 0,5 0,6 0,7 0,8 0,9 1,0 0 2 4 6 8 YEARS PROBABILITY 4EP; 84% at 4 years 3BEP; 90% at 4 years
- 20. GETUG T93 trial: 3 BEP vs 4 EP Logrank p=0.14 BEP: 5 deaths EP: 12 deaths Median follow-up = 51 months Culine et al., Ann Oncol 2007 Overall Survival
- 25. Time to treatment failure Overall survival Phase III intergroup US trial Intermediate/poor risk pts n= 219 2 BEP + 2 HDCT (CBDCA, VP16, CPM) Motzer, J Clin Oncol 2007; 25: 247-256 4 BEP R
- 26. Poor prognosis NSGCT: Randomized trials Courtesy of S. Culine Chemotherapy Number of patients Favorable response rates (%) Conclusion Reference BEP x 4 v BEP 200 x 4 78 81 73 68 Double dose cisplatin not superior and more toxic Nichols 1991 BEP x 4 v BEP/PVB x 4 125 125 76 72 Alternating regimen not superior and more toxic de Wit 1995 BEP x 4/EP x 2 v BOP/VIP-B 190 190 57 54 Dose dense alternating regimen not superior and more toxic Kaye 1998 BEP x 4 v VIP x 4 148 151 60 63 Substitution of ifosfamide for bleomycin not superior and more toxic Nichols 1998 P 200 VBE x ¾ v P 200 VBE x 2 + P 200 EC 58 57 75 67 High dose chemotherapy not superior and more toxic Droz 2007 BEP x 4 v BEP x 3 + CaEC 111 108 55 56 High dose chemotherapy not superior and more toxic Motzer 2007 BEP x 4 v CISCA/VB 96 94 61 54 Alternating regimen not superior and more toxic Culine 2008
- 29. Overall survival according to tumor marker decline at day 21 or day 42 TM assessed at Day 21 Fizazi, J Clin Oncol 2004, 22: 3868-76 Motzer, J Clin Oncol 2007; 25: 247-256 TM assessed at Day 42
- 31. GETUG 13: dose-dense regimen BEP x 1 Taxol-BEP + Oxaliplatin (d10) + G-CSF / 3 weeks x 2 cycles Cisplatin, Ifosfamide, bleomycine + G-CSF / 3 weeks x 2 cycles
- 33. Kaplan-Meier estimate of failure-free survival according to total accrual of patients by the treating institution in trial 30895/TE13. Collette L et al. JNCI J Natl Cancer Inst 1999;91:839-846 Oxford University Press Failure-Free Survival
- 34. Kaplan-Meier estimate of overall survival according to the total accrual of patients by the treating institution in trial 30895/TE13. Collette L et al. JNCI J Natl Cancer Inst 1999;91:839-846 Oxford University Press Overall survival
- 38. HD chemotherapy for 2 nd line: IT94 phase III trial n= 280 1994-2001
- 39. IT94: Overall survival Pico et al., Ann Oncol 2005, 16: 1152-1159 Conclusion: No demonstrated benefit for single HD chemotherapy
- 40. Single vs Sequential HD chemotherapy for salvage Lorch A et al., J Clin Oncol 2007, 25: 2778-84 n= 230 pts 1 VIP + 3 HD CE 3 VIP + 1 HD CEC R Accrual stopped for tox (B) No difference in outcome Sequential CT better tolerated OS PFS EFS
Editor's Notes
- Kaplan-Meier estimate of failure-free survival according to total accrual of patients by the treating institution in trial 30895/TE13. O = number of events; N = number of patients in each group. Two-sided P = .018 in stratified analysis; hazard ratio of institutions that entered fewer than five patients versus institutions that entered five patients or more = 1.56 (95% confidence interval = 1.09-2.27). The 1-year failure-free survival rate was 43% (95% confidence interval = 29%-56%) in the institutions that entered fewer than five patients and 59% (95% confidence interval = 54%-65%) in those that entered five patients or more. At 2 years, the failure-free survival rates were 38% (95% confidence interval = 25%-51%) and 55% (95% confidence interval = 50%-61%) in the two groups of institutions, respectively.
- Kaplan-Meier estimate of overall survival according to the total accrual of patients by the treating institution in trial 30895/TE13. O = number of deaths; N = number of patients in each group. Two-sided P = .010 in stratified analysis; hazard ratio of institutions that entered fewer than five patients versus institutions that entered five patients or more = 1.85 (95% confidence interval = 1.16-3.03). The 1-year survival rate was 70% (95% CI = 57%-82%) in the group that entered fewer than five patients and 82% (95% confidence interval = 78%-87%) in the group with at least five patients. The 2-year survival rates were 62% (95% confidence interval = 48%-75%) and 77% (95% confidence interval = 72%-81%) in the two groups of institutions, respectively.