An Open-Label, Multi-Centre, Safety Study of Fixed-Dose Durvalumab in Advanced Solid Malignancies (STRONG Study).

Study Design: 
867 patients with urothelial or non-urothelial urinary tract carcinoma (UTC) who progressed during or after one platinum or non-platinum chemotherapy regimen were treated with fixed dose durvalumab (1500 mg every four weeks) to progressive disease. Thirteen percent of patients had an ECOG performance status (PS) of 2, but most had an ECOG PS of 0-1.
Checkpoint inhibition has demonstrable activity in patients with locally advanced or metastatic urothelial carcinoma refractory to platinum chemotherapy. Durvalumab has previously demonstrated safety and efficacy in patients at 10 mg/kg dosed every 2 weeks. This trial evaluates a fixed dose of 1500 mg given every 4 weeks, a more convenient dosing schedule. Furthermore, it does so in a “real-world” clinical setting as patients could have non-urothelial histology and could have progressed or not responded to platinum or non-platinum chemotherapy.
The primary end-point was the incidence of adverse events of special interest (AESIs), including immune-mediated AEs (imAEs). Secondary end-points included overall survival (OS), objective response rate (ORR), and disease control rate (at six and 12 months) (DCR).
Durvalumab at a fixed dose was well tolerated. Of note, PD-L1 expression was available in 577 patients and tumor expression of PD-L1 was high in 239 (41%). Despite this finding, median OS was only 7 months in this fixed dose study compared to a previous study of durvalumab (study 1108) showing a median OS of 11 months. This is felt to be due to the “all-comers” status of this current trial with 13% of patients having ECOG PS of 2 and patients with nonurothelial histology. Although Durvalumab had attained Accelerated Approval by the FDA in urothelial cancer, failure of the DANUBE study in the first line setting, caused the company to voluntarily withdraw durvalumab from the US market. The data is nonetheless encouraging in the STRONG study that revealed durable clinical activity in previously chemotherapy-treated patients with advanced urothelial or nonurothelial urinary tract carcinoma.
Median treatment duration was 12.1 weeks and 31% were alive and being followed for survival. The median follow-up for patients was 13.8 months. AEs of any grade occurred in 787 patients (91%) with the most common being asthenia (27%), constipation (20%), and anemia (21%). AESIs of any grade occurred in 51% of patients (8% grade ≥ 3). The incidence of imAEs was 11% (2% grade ≥ 3). The median OS was 7.0 months (95% confidence interval [CI]: 6.4–8.2) and ORR was 18% (95% CI: 14.8–20.6), with complete responses in 5% of patients and a disease control rate at six months of 19% (95% CI: 16.1–22.1).