In a phase I/II study reported in the Journal of Clinical Oncology, Massard et al found that the anti–PD-L1 (programmed cell death ligand 1) antibody durvalumab was active in patients with previously treated advanced urothelial bladder cancer. Objective response appeared to be confined to patients with PD-L1–positive tumors. Neil H. Segal, MD, PhD, of Memorial Sloan Kettering Cancer Center, is the corresponding author of this article.
The reported analysis included an expansion cohort of advanced urothelial bladder cancer patients within a larger phase I/II study in patients with inoperable or metastatic tumors. The study is ongoing.
Durvalumab was given intravenously at 10 mg/kg every 2 weeks for up to 12 months to 61 patients; 93% had received at least one prior therapy for advanced disease. Exploratory analysis of pretreatment biopsies resulted in the definition of PD-L1–positive as expression of membrane PD-L1 by ≥ 25% of tumor cells or tumor-infiltrating immune cells. Forty patients were PD-L1–positive.
A total of 42 patients were considered evaluable for response; 19 were not evaluable due to initiating treatment < 12 weeks before data cutoff (n = 17) or withdrawing consent before the first post-baseline assessment (n = 2).
The median duration of follow-up was 4.3 months. Among the 61 patients included in the safety analysis, the most common treatment-related adverse events of any grade were fatigue (13%), diarrhea (10%), and decreased appetite (8%). Grade 3 treatment-related adverse events were observed in three patients (4.9%). One treatment-related adverse event (acute kidney injury) resulted in treatment discontinuation.
Among the 42 evaluable patients, the objective response rate was 31.0% (95% confidence interval [CI] = 17.6%–47.1%), with response observed in 13 of 28 PD-L1–positive patients (46.4%, 95% CI = 27.5%–66.1%) and in 0 of 14 PD-L1–negative patients (0%, 95% CI = 0.0%–23.2). Disease control rates were 57.1% and 28.6%. Responses were ongoing at last analysis in 12 of 13 patients, with the median duration of response not yet reached and durations ranging from 4.1+ to 49.3+ weeks.
The investigators concluded:
Durvalumab demonstrated a manageable safety profile and evidence of meaningful clinical activity in PD-L1–positive patients with [urothelial bladder cancer], many of whom were heavily pretreated.
The durvalumab study was supported by MedImmune. ■
Massard C, et al: J Clin Oncol. June 6, 2016 (early release online).