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Randomized phase II/III trial comparing gemcitabine/ carboplatin (GC) and methotrexate/carboplatin/

vinblastine (M-CAVI) in patients (pts) with advanced urothelial cancer (UC) unfit for cisplatin-based

chemotherapy (CHT): Phase III results of EORTC study 30986

Authors: De Santis M et al, ASCO 2010Abstract: LBA4519Reviewed by: Dr. Lori WoodDate posted: Jun 18 2010

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STUDY RATIONALE

• Up to 50% of pateints with metastatic urothelial cancer are not eligible for standard dose cisplatin due to creatinine clearance, performance status, and co-morbidities

• Difficult to know how to treat unfit patients with metastatic urothelial cancer

• Also, there is no clear consensus on how to define “unfit”– For this study: based on ECOG PS and GFR

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R

Treatment A: M-CAVI:Methotrexate 30 mg/m2 d1, d15, d22Carboplatin AUC 4.5 d1Vinblastine 3 mg/m2 d1, d15, d22q4wksN=119

Treatment B: GC:Gemcitabine 1000 mg/m2 d1 and d8Carboplatin AUC 4.5 d1q3wksN=119

STUDY DESIGN

- Metastatic TCC- Unfit patients: - PS 2 and/or - GFR 30-60 ml/min- Primary outcome: - overall survival- Statistics: - median OS 9.0m 13.5m with GC

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RESULTS

GC MCAVI HR P valuePS 0

1

2

16.8%

38.7%

44.5%

16%

38.7%

45.4%

Visceral Metastases 46.2% 55.5% SS

GFR 60 ml/min 55% 55%

RECIST RR 41.2% 30.3% p=0.01

PFS 5.8m 4.2m p=0.78

OS 9.3m 8.1m 0.94 p=0.64

Median follow-up = 4.5 years

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RESULTS: TOXICITY

GC MCAVI P value

Grade 3/4 Thrombocytopenia 48.3% 19.4% SS

Febrile Neutropenia 4.2% 14.4% SS

Severe/Acute Toxicity

(predefined definition)9.3% 21.2% SS

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STUDY COMMENTARY

• Gemcitabine/Carboplatin did not increase overall survival compared to Methotrexate, Carboplatin, Vinblastine

• It was somewhat more tolerable

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BOTTOM-LINE FOR CANADIAN MEDICAL ONCOLOGISTS

• Most Canadian medical oncologists would not be using Methotrexate, Carboplatin and Vinblastine as their standard therapy for unfit patients

• Most would be using:– Gemcitabine alone– Gemcitabine/Carboplatin

• This trial supports the use of Gem/Carbo given that it does not have a worse outcome and does have a better tolerability

• This trial also gives a modern day median survival for unfit bladder cancer patients based on the Bajorin (MSKCC) risk factors (poor PS and presence of visceral metastases)– 0 factors = 12m– 1 factor = 9.3m – 2 factors = 5.5m