Impact of prior platinum agent and site of primary in patients with advanced urothelial carcinoma (UC) receiving salvage therapy.

Abstract

336 Background: The prognostic impact of prior platinum agent (cisplatin vs. carboplatin) and site of primary (bladder vs. other) in the context of salvage therapy for advanced UC is unknown. Methods: We pooled 10 prospective phase II trials of ≥ second-line therapy for advanced UC with data recorded for prior platinum agent and site of primary in addition to major prognostic factors: TFPC (time from prior chemotherapy), Hb (hemoglobin), PS (performance status), and LM (liver metastasis) status. Cox proportional hazards regression was used to evaluate the association of prior platinum agent and site of primary with overall survival (OS) and progression-free survival (PFS). Trial was included as a stratification factor throughout. Kaplan-Meier method was used to estimate PFS and OS. Results: Of 731 patients overall, 559 had received one prior chemotherapy regimen, 663 were evaluable for prior platinum regimen and 512 for site of primary. The overall median PFS and OS were 2.7 and 6.8 months, respectively. The trials evaluated vinflunine (N=151), docetaxel +/- vandetanib (N=148), paclitaxel-gemcitabine (N=98), sunitinib (N=77), volasertib (N=50), nab-paclitaxel (N=48), everolimus (N=45), pazopanib (N=43), cetuximab +/-paclitaxel (N=39) and paclitaxel-cyclophosphamide (N=32). Prior platinum was cisplatin in 501 (75.6%) and carboplatin in the rest. Prior carboplatin was associated with worse OS on univariate analysis (HR 1.23 [1.00-1.52], P=0.048) but not significantly associated with either OS or PFS on multivariate analysis. Bladder was the site of primary in 388 (75.8%). The site of primary was not significantly associated with PFS and OS in either univariate or multivariate analyses. Conclusions: Neither prior platinum agent (cisplatin vs. carboplatin) nor site of primary (bladder vs. other) were independently associated with OS or PFS in patients receiving salvage therapy for advanced UC. Trials of salvage therapy may continue to utilize the previously recognized prognostic factors, and could allow patients with all sites of primary disease and regardless of the prior platinum agent. These data need external validation.