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ASCO 2010

Randomized 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:


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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


Heng et al Onc Reviews 2008 2:4-8


R

Paclitaxel 80mg/m2 d1,8Gemcitabine 1000 mg/m2 d1,8Cisplatin 70 mg/m2 d14 cycles n=68

Observation

N=74Resected

Muscle InvasiveT3,4 and/or N+Transitional Cell

CarcinomaECOG 0-1

CrCl>50ml/min

Primary Outcome:Overall Survival15% in 2-y OS

50% 65%HR=0.77

STUDY DESIGN

Median follow-up 29.8 months


PATIENT CHARACTERISTICS

PGC Observation

Median Age (yrs) 63 62.5

Performance Status

0

1

56%

44%

59%

41%

Stage

T3N0

T4N0

Any T N1

Any T N2

Any T N3

31%

16%

29%

22%

1.5%

27%

13.5%

30%

28%

1%


RESULTS

PGC Observation HRp-value

DFS (median,

mos) 36* 10* 0.38 <0.0001

OS

(median, mos)

NR 26 0.44 <0.0009

*Estimated from Kaplan Meier Curve


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.


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

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