Cisplatin-based regimens are the mainstay of treatment (tx) for mUC. Unfortunately, pts with mUC are often elderly and have comorbid conditions that preclude cisplatin-based tx. This CTEP-sponsored trial seeks to assess the efficacy and tolerability of GE in this population.
A Simon 2 stage design was employed (7 + 14). To proceed to full accrual first stage required 2 or more confirmed responders- complete (CR) or partial (PR) response. To be a positive trial, 7 responders were required. Tx consisted of Gemcitabine 1gm/m2 and Eribulin 1.4mg/m2, both on Day (D) 1 and D8 of a 21-D cycle and continued until progression (PD) or unacceptable toxicities. Cisplatin ineligibility was defined as creatinine clearance (CrCl)
Between 6/2015 and the report cutoff date of 5/2017, 24 eligible pts with a median age of 73 (range: 62-88) were enrolled. Demographics: 20 males, 4 females. ECOG performance status of 0/1/2 was seen in 11/11/2 pts. Sites of disease included: nodes 16, lungs 8, liver 7, bladder 5, bones 2. Median number of cycles was 3.5 (range 1-16). 2+ confirmed PRs in the first 7 pts allowed the trial to proceed to full accrual. Of 19 evaluable pts, 2 had a CR, 10 had a PR, 5 had SD and 1 had PD. The objective response rate (ORR) was 63%. Overall survival (OS) 14.9 months (5.6, 21.9+) and progression free survival (PFS) was 6.9 months (5.3, 16.1+). Duration of response (DOR) was 4.6 months (range: 0.5, 15.0). Among the first 21 pts 7 had a PR and 2 had a CR and 5 were inevaluable for response, with an ORR of 43%. All 24 pts were evaluable for toxicities; the most common any grade toxicities included fatigue 83%, neutropenia 75%, anemia 63%, alopecia 50%, elevated AST 46%, constipation and nausea 42% each and thrombocytopenia 36%.
GE exceeded the threshold for efficacy in this trial. The endpoints of ORR, OS and PFS compare favorably to the commonly used regimens in this setting such as gemcitabine-carboplatin with a confirmed ORR of 36.1% and OS of 9.3 months. These data support further development of this combination in pre-and post immunotherapy settings.
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All authors have declared no conflicts of interest