BACKGROUND: There are a lack of published real-world data on treatmentpatterns for patients with locally advanced or metastatic urothelial carcinoma(la/mUC) previously treated with programmed death 1/ligand 1 inhibitor (PD-1/L1i) therapy. The objective of this study was to characterize the clinicalcharacteristics and treatments among patients with la/mUC followingdiscontinuation of first-line (1L) or second-line (2L) PD-1/L1i therapy.
METHODS: We performed a retrospective chart review at 26 geographicallydiverse clinical sites in the US. Patients aged ≥18 years with histologically orcytologically confirmed urothelial carcinoma and radiographic evidence ofmetastatic or locally advanced disease were identified. Included patients hadinitiated and subsequently discontinued PD-1/L1i therapy in the 1L or 2L settingfor la/mUC between May 15, 2016-July 31, 2018. All patients had follow-upthrough October 31, 2019. Data were summarized using descriptive statistics.
RESULTS: Among the 300 patients included in the chart review, 198 (66%)received PD-1/L1i therapy as 1L and 102 (34%) as 2L therapy. Mean (SD) age atla/mUC diagnosis was 69.4 (8.7) years, and a majority of patients were male(66.0%) and White (74.7%). Consistent with age, most patients (82.7%) hadcomorbidities at la/mUC diagnosis; 39.7% hypertension, 23.7% coronary arterydisease, 17.7% pulmonary disease, and 9.3% renal disease. At initiation oftherapy, a higher proportion of patients who received 1L PD-1/L1i therapy had anEastern Cooperative Oncology Group performance status of 2 or more thanpatients who received 2L PD-1/L1i therapy (36.8% vs 22.5%, respectively).Following discontinuation of PD-1/L1i therapy, 34% (n = 68) received subsequenttherapy in 2L and 29% (n = 30) in third-line (3L). The most common subsequenttherapies in 2L were gemcitabine monotherapy (24%), gemcitabine plus cisplatinor carboplatin (22%), PD-1/L1i therapy (22%), and taxane monotherapy (19%).The most common subsequent therapies received in 3L were taxanemonotherapy (50%), pemetrexed (17%), and PD-1/L1i therapy (16%). Overall,switching from one PD-1/L1i therapy to another distinct PD-1/L1i therapyoccurred in approximately 20% of patients, with “better efficacy/survival” notedby treatment teams as the most common reason for switching therapy amongthis subgroup.
CONCLUSIONS: In this real-world case series, only a minority of patients withla/mUC who discontinued PD-1/L1i therapy received subsequent therapy.Among those that did, no clear standard of care was observed andapproximately one-fifth of patients were treated with a second PD-1/L1i therapy after the first failed to control disease. Collectively, the data highlight significant unmet need for patients with la/mUC who discontinue PD-1/L1i therapy.
