Gemcitabine and cisplatin versus methotrexate, vinblastine, doxorubicin, and cisplatin in advanced or metastatic bladder cancer: trial

Gemcitabine and cisplatin versus methotrexate, vinblastine, doxorubicin, and cisplatin in advanced or metastatic bladder cancer

Phase 3N = 405

Population

Stage IV transitional-cell carcinoma of the urothelium (locally advanced or metastatic) with no prior systemic chemotherapy

Design

Randomised, multinational, multicentre phase 3 study; gemcitabine 1,000 mg/m2 days 1, 8 and 15 plus cisplatin 70 mg/m2 day 2, or standard MVAC, every 28 days for a maximum of six cycles.

Arms

Gemcitabine plus cisplatin (experimental, n = 203): Gemcitabine 1,000 mg/m2 days 1, 8, 15 plus cisplatin 70 mg/m2 day 2 every 28 days, maximum six cycles
MVAC (control, n = 202): Standard MVAC (methotrexate, vinblastine, doxorubicin, cisplatin) every 28 days, maximum six cycles

People

von der Maase H

OSHR 1.04 (95% CI 0.82–1.32)TTPHR 1.05 (95% CI 0.85–1.30)Δ ORR+3 pointsΔ Toxic death rate−2 pointsOSHR 1.09 (95% CI 0.88–1.34)Δ median OS−1.2 months

Show the numbers

Results reported for Gemcitabine and cisplatin versus methotrexate, vinblastine, doxorubicin, and cisplatin in advanced or metastatic bladder cancer
Endpoint	Analysis	Gemcitabine plus cisplatin	MVAC	Effect
OSAll randomised patients (n = 405)	primaryvon 2000	—	—	HR 1.04 (95% CI 0.82–1.32)P=.75
TTPAll randomised patients (n = 405)	primaryvon 2000	—	—	HR 1.05 (95% CI 0.85–1.30)Time to treatment failure HR 0.89 (95% CI 0.72 to 1.10) was also reported.
ORRAll randomised patients (n = 405)	primaryvon 2000	49%	46%	Reported as 'response rate'; no confidence intervals in the abstract.
Toxic death rateAll randomised patients (n = 405)	primaryvon 2000	1%	3%	—
OSAll randomised patients (n = 405)	long term-updatevon 2005	median 14 months; 13% at 5 y	median 15.2 months; 15.3% at 5 y	HR 1.09 (95% CI 0.88–1.34)P=0.665-year OS rates compared with P = .53. 347 patients had died at the time of analysis.
PFSAll randomised patients (n = 405)	long term-updatevon 2005	median 7.7 months; 9.8% at 5 y	median 8.3 months; 11.3% at 5 y	HR 1.09P=0.63The abstract gives no confidence interval for the PFS hazard ratio; P = .63 refers to the 5-year PFS rates.

Results reported for Gemcitabine and cisplatin versus methotrexate, vinblastine, doxorubicin, and cisplatin in advanced or metastatic bladder cancer
Endpoint	Analysis	Gemcitabine plus cisplatin	MVAC	Effect
OSAll randomised patients (n = 405)	primaryvon 2000	—	—	HR 1.04 (95% CI 0.82–1.32)P=.75
TTPAll randomised patients (n = 405)	primaryvon 2000	—	—	HR 1.05 (95% CI 0.85–1.30)Time to treatment failure HR 0.89 (95% CI 0.72 to 1.10) was also reported.
ORRAll randomised patients (n = 405)	primaryvon 2000	49%	46%	Reported as 'response rate'; no confidence intervals in the abstract.
Toxic death rateAll randomised patients (n = 405)	primaryvon 2000	1%	3%	—
OSAll randomised patients (n = 405)	long term-updatevon 2005	median 14 months; 13% at 5 y	median 15.2 months; 15.3% at 5 y	HR 1.09 (95% CI 0.88–1.34)P=0.665-year OS rates compared with P = .53. 347 patients had died at the time of analysis.
PFSAll randomised patients (n = 405)	long term-updatevon 2005	median 7.7 months; 9.8% at 5 y	median 8.3 months; 11.3% at 5 y	HR 1.09P=0.63The abstract gives no confidence interval for the PFS hazard ratio; P = .63 refers to the 5-year PFS rates.

Hazard ratio (95% CI) by endpoint. Values below 1 favour the experimental arm.

Data table

Endpoint	HR	95% CI
OS	1.04	0.82–1.32
TTP	1.05	0.85–1.3
OS	1.09	0.88–1.34

Illustrative — modelled from reported values, not trial data. OS, long term-update.

Show curves

Gemcitabine plus cisplatin (experimental)
MVAC (control)

Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.

Data table (modelled values)

Months	Gemcitabine plus cisplatin	MVAC
0	100.0%	100.0%
10	61.0%	63.4%
19	39.0%	42.0%
29	23.8%	26.6%
38	15.2%	17.7%

Illustrative — modelled from reported values, not trial data. PFS, long term-update.

Show curves

Gemcitabine plus cisplatin (experimental)
MVAC (control)

Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.

Data table (modelled values)

Months	Gemcitabine plus cisplatin	MVAC
0	100.0%	100.0%
5	63.8%	65.9%
10	40.6%	43.4%
16	23.7%	26.3%
21	15.1%	17.3%

Appears in

2000 Gemcitabine-cisplatin compared with MVAC in advanced bladder cancer

Sources

von der Maase H, Hansen SW, Roberts JT, Dogliotti L, Oliver T, Moore MJ, et al. Gemcitabine and cisplatin versus methotrexate, vinblastine, doxorubicin, and cisplatin in advanced or metastatic bladder cancer: results of a large, randomized, multinational, multicenter, phase III study. J Clin Oncol. 2000;18(17):3068-77.
PubMed DOI
von der Maase H, Sengelov L, Roberts JT, Ricci S, Dogliotti L, Oliver T, et al. Long-term survival results of a randomized trial comparing gemcitabine plus cisplatin, with methotrexate, vinblastine, doxorubicin, plus cisplatin in patients with bladder cancer. J Clin Oncol. 2005;23(21):4602-8.
PubMed DOI