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1. ASCO 2010Randomized phase III trial comparing adjuvant paclitaxel/gemcitabine/cisplatin (PGC) to observation in patients with resected invasive bladder cancer: Results of the Spanish Oncology Genitourinary Group (SOGUG) 99/01 study L. G. Paz-Ares, E. Solsona, E. Esteban, A. Saez, J. Gonzalez-Larriba, A. Anton, M. Hevia, F. de la Rosa, V. Guillem, J. Bellmunt Reviewed by: Dr. Daniel Heng and Dr. Lori Wood Abstract: LBA4518 Date posted:

2. Thank you for downloading this update. Please feel free to use it for educational purposes. Please acknowledge OncologyEducation.ca and Drs Heng and Wood when using these slides.

3. BACKGROUND • Cisplatin and gemcitabine neoadjuvant chemotherapy is a standard of care for muscle-invasive bladder cancer • Adjuvant chemotherapy is also a standard of care post cystectomy. However, the clinical trials involving adjuvant therapy have been plagued with small sample size and premature closure and clinicians tend to extrapolate the neoadjuvant data to justify adjuvant chemotherapy • Role of adjuvant chemotherapy remains a very relevant clinical question in 2010

4. Heng et al Onc Reviews 2008 2:4-8

5. STUDY DESIGN Paclitaxel 80mg/m2 d1,8 Gemcitabine 1000 mg/m2 d1,8 Cisplatin 70 mg/m2 d1 4 cycles n=68 R Primary Outcome: Overall Survival 15%  in 2-y OS 50%  65% HR=0.77 Observation N=74 Resected Muscle Invasive T3,4 and/or N+ Transitional Cell Carcinoma ECOG 0-1 CrCl>50ml/min Median follow-up 29.8 months

6. PATIENT CHARACTERISTICS

7. RESULTS *Estimated from Kaplan Meier Curve

8. STUDY COMMENTARY • This study was closed early due to poor accrual (142 patients out of a planned 340) • The use of observation as a standard of care is controversial and may have altered the type of patients enrolled into this study. • PGC was a tolerable regimen but there was significant grade 3/4 neutropenia (febrile neutropenia 9.5%) and there was one toxic sepsis death.

9. BOTTOM LINE FOR CANADIAN MEDICAL ONCOLOGISTS • This study was an attempt at determining the efficacy of adjuvant chemotherapy and to examine a triplet as opposed to the conventional cisplatin/gemcitabine doublet regimen. • Although cross-trial comparisons cannot be made, the large improvement of OS (5 yr OS 60% vs 31%) and DFS with adjuvant chemotherapy over observation is larger than what has been demonstrated from neoadjuvant therapy trials. • This may be due to patient selection, bias, or perhaps a true benefit of adding a taxane adjuvantly. This trial was not designed to answer the latter question. • Because the study was prematurely closed due to poor accrual, firm conclusions cannot be made • Presumably the poor accrual to these adjuvant trials is due to a bias (physician and patient) against observation alone • The EORTC study ( NCIC BL.8) also closed early due to poor accrual (after ~340 pts) and perhaps these 2 trials can pool data • Adjuvant Chemotherapy in this setting still remains unresolved