The U.S. Food and Drug Administration has granted accelerated approval to durvalumab for the treatment of patients with locally advanced or metastatic urothelial carcinoma who have disease progression during or following platinum-containing chemotherapy or who have disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy.

The FDA also approved the VENTANA PD-L1 (SP263) assay as a complementary diagnostic for the assessment of the PD-L1 protein in formalin-fixed, paraffin-embedded urothelial carcinoma tissue.

Approval was based on one single-arm trial of 182 patients with locally advanced or metastatic urothelial carcinoma whose disease progressed after prior platinum-containing chemotherapy.

Durvalumab, 10 mg/kg intravenously, was administered every 2 weeks.

Confirmed objective response rate (ORR) as assessed by blinded independent central review per RECIST 1.1, was 17.0% (95% CI: 11.9, 23.3).

At the data cutoff for the ORR analysis, median response duration was not reached (range: 0.9 to 19.9 months).

ORR was also analysed by PD-L1 expression status as measured by VENTANA PD-L1 (SP263) Assay.

In the 182 patients, the confirmed ORR was 26.3% (95% CI: 17.8, 36.4) in 95 patients with a high PD-L1 score and 4.1% (95% CI: 0.9, 11.5) in 73 patients with a low or negative PD-L1 score.

The most common adverse reactions in at least 15% of patients were fatigue, musculoskeletal pain, constipation, decreased appetite, nausea, peripheral oedema, and urinary tract infection.

Grade 3-4 adverse events were seen in 43% of patients. Infection and immune-related adverse events such as pneumonitis, hepatitis, colitis, thyroid disease, adrenal insufficiency, and diabetes were also seen with durvalumab.

The recommended dose of durvalumab is 10 mg/kg, administered as an intravenous infusion over 60 minutes every 2 weeks until disease progression or unacceptable toxicity.

Full prescribing information is available here.

Durvalumab is also under investigation in the Phase III DANUBE trial as first-line treatment in urothelial carcinoma as monotherapy and in combination with tremelimumab.

Nicholas J. Vogelzang, MD, FACP, FASCO, Clinical Professor at the University of Nevada School of Medicine; SWOG GU Vice Chair; US Oncology Research GU Chair; Comprehensive Cancer Centers of Nevada, said “The usual course of treatment for patients with advanced bladder cancer begins with a standard platinum-containing chemotherapy. Patients who have disease progression during or following chemotherapy are left with few other treatment options. The approval of durvalumab to treat this population of select patients signifies hope for those who are currently suffering, or may find themselves with limited options in the future.”

Source: FDA & Businesswire