Bladder Cancer · Medical · Advanced / Metastatic

EORTC 30986

In advanced urothelial carcinoma patients unfit for cisplatin, does gemcitabine/carboplatin improve efficacy or severe toxicity compared with M-CAVI?

Population238 chemotherapy-naive patients with measurable advanced urothelial cancer and impaired renal function and/or performance status 2.InterventionGemcitabine + carboplatin.ComparatorMethotrexate + carboplatin + vinblastine (M-CAVI).Primary phase III endpointOverall survival.

Absolute Effect

Overall survival

Median OS 9.3 vs 8.1 months

GC versus M-CAVI; P=.64. No significant OS difference.

Severe acute toxicity

9.3% vs 21.2%

Absolute reduction 11.9 percentage points with gemcitabine/carboplatin.

Response

ORR was 41.2% with GC versus 30.3% with M-CAVI (P=.08). Confirmed response was 36.1% vs 21.0%.

Clinical interpretation

The major randomized signal was lower severe acute toxicity with similar survival, rather than a proven survival advantage.

The trial specifically addresses patients who cannot receive cisplatin; the results should not be extrapolated to cisplatin-eligible patients.

NNT / NNH

For severe acute toxicity, the absolute reduction of 11.9 percentage points corresponds to an approximate NNT of 9 to prevent one severe acute toxicity event. For OS, NNT is not appropriate because the survival difference was not statistically significant.

Limitations

The study enrolled a clinically frail population. Performance status 2 and renal impairment were important modifiers of both treatment tolerance and outcome.

Primary / authoritative sources

EORTC 30986 phase II/III report — PubMed

Phase II report — PubMed