authors: de wit r. et al, asco 2011 abstract: 4509 reviewed by: dr. lori wood

www.OncologyEducation.ca

A randomized phase III study comparing paclitaxel-BEP (T-BEP) to standard BEP in patients with

intermediate prognosis germ cell cancer (GCC): An intergroup study of EORTC, German TCSG/AUO, MRC, and Spanish GCC group (EORTC 30983).

Authors: de Wit R. et al, ASCO 2011Abstract: 4509Reviewed by: Dr. Lori WoodDate posted: June 2011

www.OncologyEducation.ca

Thank you for downloading this update. Please feel free to use it for educational purposes.

Please acknowledge OncologyEducation.ca and Dr. Lori Wood when using these slides.

www.OncologyEducation.ca

STUDY RATIONALE

• Since 1985, BEP chemotherapy is the gold standard treatment for all patients with metastatic GCTs– Cisplatin 20 mg/m2 d1-5– Etoposide 100 mg/m2 d1-5– Bleomycin 30 iu d2, d9, d16

• There are patients with intermediate and poor risk disease who still die of metastatic GCTs despite BEP

• There is a need to improve on standard BEP• Paclitaxel has shown activity in first-line and relapsed

GCTs• The idea was to bring Paclitaxel into the first-line setting

– 175 mg/m2 d1

www.OncologyEducation.ca

R

Treatment A: BEP + Paclitaxel x 4T-175 mg/m2 d1n=168GCSF

Treatment B:BEP x 4n=169

STUDY DESIGN

- IGCCC- Intermediate prognosis metastatic GCTs-Statistics: - 10% in 3-y PFS from 75% 85% - planned n=498 - closed with n=337 due to slow/poor accrual

www.OncologyEducation.ca

RESULTS

T-BEP BEP

n 168 169

Ineligible• good risk• poor risk

13

6

4

13

8

1

No Baseline Data 3 3

Eligible Patients 148 152

- Phase II accrual from November 1999 – March 2004. - Phase III accrual from March 2004 – August 2009 and then closed early. - Median follow-up = 5.3 years.

www.OncologyEducation.ca

RESULTS

T-BEP BEP HR p Value

N 168 169

Completed 4 Cycles 87.5% 92.3%

CR with Chemotherapy Only 65.1% 52.3%

CR with Chemotherapy/Surgery 70.4% 59.5% 0.055

3-y PFS (ITT) 79.4% 71.1%0.73

(0.47-1.13)0.153

3-y PFS (Eligible Patients) 82.7% 70.1%0.60

(0.37-0.97)0.03

3-y OS (ITT) 91.2% 89.8% 0.89 0.738

www.OncologyEducation.ca

STUDY COMMENTARY

• Primary endpoint of 3-y PFS was not met– But ineligible patients unbalanced between

the two arms

• Primary endpoint of eligible patients only – T-BEP better– 82.7% vs. 70.1% 3-y PFS

• Speculated that this was due to imbalance of ineligible patients between the two arms

• Two toxic deaths associated with T-BEP (1.3%)

www.OncologyEducation.ca

BOTTOM-LINE FOR CANADIAN MEDICAL ONCOLOGISTS

• Intriguing results but a positive trial only when data looked at eligible patients and not intention to treat analysis

• Given the great research question, it is hard to believe this study could not accrue and this fact really hurt this study

• I do not think we can incorporate these results into every day practice at this time