Background: This is an update of the safety and efficacy of durvalumab monotherapy in pts with locally advanced/metastatic urothelial carcinoma (UC) from an ongoing, phase 1/2 open-label study (NCT01693562).

Methods: Pts received 10 mg/kg every 2 weeks up to 12 months or until unacceptable toxicity, progression, or starting another anticancer therapy. Pts were stratified by tumor PD-L1 expression (Ventana PD-L1 [SP263] Assay [PD-L1 cutoff: ≥25% of tumor cells and/or immune cells with membrane staining]) and treatment line.

Results: As of the data cutoff (16Oct2017), 201 UC pts with Stage IV disease received treatment, with a median follow-up of 16.9 months (range, 0.4-37.7). Across treatment lines, objective response rate (ORR) by blinded independent central review was 17.4% (95% CI, 12.4, 23.4) in all pts; 27.5% in the PD-L1 ≥25% group vs 5.8% in the PD-L1 <25% group. The responses have been durable regardless of PD-L1 status, with the median duration of response not yet reached in the PD-L1 ≥25% group and 12.2 months in the PD-L1 <25% group. Responses lasted ≥12 mo in 62.9% of responders (max 25.7+ mo). Overall, median OS was 10.5 months (95% CI, 6.9, 15.7); 19.8 months in the PD-L1 ≥25% group vs 4.8 months in the PD-L1 <25% group (Table). Pts previously treated with platinum based chemotherapy also reported similar durable responses. At least one treatment-related AE was reported in 120 pts (59.7%), including fatigue (39 [19.4%]), decreased appetite and rash (18 [9.0%] each), and diarrhea (16 [8.0%]). Grade 3/4 treatment-related AEs occurred in 19 (9.5%) pts; 6 (3.0%) treatment discontinuations and 2 (1.0%) deaths were attributed to treatment-related AEs.

Conclusions: With extended follow-up, durvalumab continues to show durable clinical activity in UC pts, especially in the PD-L1 ≥25% group with an acceptable toxicity profile.

 PD-L1 ≥25% PD-L1 <25% PD-L1 unknown Total 
All UC n=102 n=86 n=13 N=201 
Confirmed ORR, % 27.5 5.8 15.4 17.4 
(95% CI) (19.1, 37.2) (1.9, 13.0) (1.9, 45.4) (12.4, 23.4) 
CR, % 7.8 3.5 7.7 6.0 
PR, % 19.6 2.3 7.7 11.4 
Median DoR, months NR 12.2 NR NR 
(min, max) (2.7, 25.7+) (8.6, 21.7+) (14.5+, 14.6+) (2.7, 25.7+) 
Median PFS, months (95% CI) 1.9 (1.4, 2.7) 1.4 (1.3, 1.5) 2.8 (1.4, NE) 1.5 (1.4, 1.8) 
6-month PFS rate, % 28.6 8.6 25.2 20.4 
12-month PFS rate, % 22.3 7.1 25.2 16.2 
Median OS, months (95% CI) 19.8 (9.3, NE) 19.8 (9.3, NE)4.8 (3.3, 8.1) NR (4.9, NE) 10.5 (6.9, 15.7) 
6-month OS rate, % 67.6 45.8 69.2 58.9 
12-month OS rate, % 57.6 29.5 61.5 46.6 
 PD-L1 ≥25% PD-L1 <25% PD-L1 unknown Total 
All UC n=102 n=86 n=13 N=201 
Confirmed ORR, % 27.5 5.8 15.4 17.4 
(95% CI) (19.1, 37.2) (1.9, 13.0) (1.9, 45.4) (12.4, 23.4) 
CR, % 7.8 3.5 7.7 6.0 
PR, % 19.6 2.3 7.7 11.4 
Median DoR, months NR 12.2 NR NR 
(min, max) (2.7, 25.7+) (8.6, 21.7+) (14.5+, 14.6+) (2.7, 25.7+) 
Median PFS, months (95% CI) 1.9 (1.4, 2.7) 1.4 (1.3, 1.5) 2.8 (1.4, NE) 1.5 (1.4, 1.8) 
6-month PFS rate, % 28.6 8.6 25.2 20.4 
12-month PFS rate, % 22.3 7.1 25.2 16.2 
Median OS, months (95% CI) 19.8 (9.3, NE) 19.8 (9.3, NE)4.8 (3.3, 8.1) NR (4.9, NE) 10.5 (6.9, 15.7) 
6-month OS rate, % 67.6 45.8 69.2 58.9 
12-month OS rate, % 57.6 29.5 61.5 46.6 

Citation Format: Peter O'Donnell, Christophe Massard, Bhumsuk Keam, Sang-We Kim, Terry Friedlander, Myung-Ju Ahn, Michael Ong, Michael Gordon, Marcus Butler, Scott Antonia, Gerardo Colon-Otero, Martin Gutierrez, Sumati Gupta, Alexander Spira, Alexandra Drakaki, Michele Maio, Feng Xiao, Natasha Angra, Shaad Abdullah, Thomas Powles. Updated efficacy and safety profile of durvalumab monotherapy in urothelial carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr CT031.