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

Samer Salah, Jae Lyun Lee, Antonio Rozzi, Hiroshi Kitamura, Kazumasa Matsumoto, Daniel J. Vis, Sandy Srinivas, Rafael Morales-Barrera, Joan Carles, Dalia Al-Rimawi, Soonil Lee, Ki Hong Kim, Kouji Izumi, Jeremy Lewin

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    3 Citations (Scopus)


    © 2016 Elsevier Inc. We pooled individual data of older patients (≥ 70 years) from 10 studies that assessed second-line chemotherapy for metastatic urothelial carcinoma. A prognostic model that separates the patients into 4 groups with significant differences in survival outcomes was developed. Furthermore, second-line combination regimens, compared with single-agent chemotherapy, were associated with increased toxicity without improved survival. 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.
    Original languageEnglish
    Pages (from-to)e563-e571
    JournalClinical Genitourinary Cancer
    Issue number4
    Publication statusPublished - 1 Aug 2017


    • Bladder neoplasm
    • Cancer metastasis
    • Geriatric oncology
    • Prognosis
    • Urological cancers


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