OBJECTIVES: Conduct a systematic literature review (SLR) of studies assessing clinical outcomes associated with pharmacological interventions in patients with locally advanced or metastatic urothelial cancer (UC) who have progressed during or after first line platinum-based chemotherapy.

METHODS: Medline, EMBASE, and conference proceedings databases were searched (2001 – 2017) to capture overall response rate (ORR), progression-free survival (PFS), duration of response (DOR) and overall survival (OS) of systemic second-line therapy. 244 articles met the predefined inclusion criteria. Review of the 76 articles relating to second-line resulted in final data extraction from four randomized controlled clinical trials (RCTs) and thirty-eight single arm studies.

RESULTS: ORR with cisplatin- and carboplatin-based regimens, vinflunine, and immuno-oncology therapies (IOs) (either single or combination regimens) ranged from 8% to 50% in RCTs and from 6% to 60% in single arm studies. Median PFS with chemotherapy ranged from 3.3 to 4.0 months in RCTs (n= 2), from 1.4 to 6.0 (n=15) in single arm studies, and from 1.1 to 4.1 (n=5) with IOs. Median OS with chemotherapy ranged from 5.3 to 13.6 months (n=23) and from 7.0 to 14.1 months (n=7) with IOs (OS from many IO studies not estimated or reported due to limited follow up). Median DOR ranged from 3.9 to 9.1 months (n= 16) with chemotherapy regimens, and was not estimable in IO studies (n=7), with >80% of responders having responses lasting ≥ 6 months.

CONCLUSIONS: There was a large variability in outcomes observed by regimen, patient population and study design. The findings of this SLR suggest a high unmet need still exists for patients who have failed or progressed after first-line treatment. This highlights the need for new treatment options that can induce durable responses in these patients. Recently approved IOs seem promising for a patient population with historically limited treatment options.