Second-line Chemotherapy in Older Patients With Metastatic Urothelial Carcinoma: Pooled Analysis of 10 Second-line Studies

Abstract

BACKGROUND: Older patients with metastatic urothelial carcinoma (UC) are under-represented in clinical trials, and data regarding outcomes for second-line therapy is limited. MATERIALS AND METHODS: Individual data for patients with metastatic UC, aged≥ 70 years, were pooled from 10 second-line studies. The influence of potential prognostic factors on overall survival (OS) was assessed via univariate and multivariate Cox regression analysis. RESULTS: In total, 102 patients were included; the median age was 74.0 years (range, 70-88 years). Second-line chemotherapy was single-agent in 42 (41%) patients and combination regimens in 60 (59%) patients. Median progression-free and OS were 4.3 and 9.7 months, respectively. In multivariate analysis, age > 75 years, Eastern Cooperative Oncology Group performance status≥ 1, serum hemoglobin< 10 g/dL, and non-lymph node only metastasis predicted inferior OS. Median OS for patients with 0, 1, 2, and≥ 3 adverse factors was unreached, 15.5, 9.8, and 4.8 months, respectively (P< .001). There was no difference in OS between patients treated with single-agent or combination chemotherapy. Combination regimens were associated with higher occurrences of any≥ grade 2 toxicity (80% vs. 38%; P< .001),≥ grade 2 hematologic (78% vs. 12%; P< .001), and≥ grade 2 gastrointestinal toxicity (36% vs. 7%; P< .001). CONCLUSION: In this pooled analysis of older patients with metastatic UC, combination chemotherapy for second-line treatment was associated with greater toxicity without improvement in OS. Eastern Cooperative Oncology Group performance status≥1, serum hemoglobin< 10 g/dL, and age > 75 years predicted worse survival, whereas isolated lymph node metastasis predicted a favorable outcome.