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Durvalumab was granted approval by the FDA for the treatment of patients with locally advanced or metastatic urothelial carcinoma (mUC) who have disease progression during or following platinum-containing chemotherapy, or whose disease has progressed within 12 months of receiving platinum-containing neoadjuvant or adjuvant chemotherapy.

  
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Durvalumab is approved under the FDA's accelerated approval pathway, based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials. It is also under investigation in the phase III DANUBE trial as first-line treatment in urothelial carcinoma as monotherapy and in combination with tremelimumab.

 

Additionally, the VENTANA PD-L1 (SP263) Assay was approved by the FDA as a complementary diagnostic to provide PD-L1 status for patients with mUC being considered for treatment with durvalumab. The test evaluates patient PD-L1 status using both tumor and immune cell staining and scoring within the tumor microenvironment, providing clinicians with information that may guide treatment decisions. Understanding the expression of PD-L1 in tumors can help identify patients most likely to benefit from immunotherapy.

 

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

 

The accelerated FDA approval of durvalumab, a human monoclonal antibody that blocks PD-L1, is based on data from Study 1108. This phase I/II trial evaluated the safety and efficacy in patients with locally advanced or mUC of the bladder. Patients had progressed while on or after a platinum-containing chemotherapy, including those who progressed within 12 months of receiving therapy in a neoadjuvant or adjuvant setting.

 

In the trial, durvalumab demonstrated rapid and durable responses, with an objective response rate of 17.0 percent (95% confidence interval [CI]: 11.9; 23.3) in all evaluable patients, regardless of PD-L1 status, and 26.3 percent (95% CI: 17.8; 36.4) in patients with PD-L1 high-expressing tumors (as determined by the VENTANA PD-L1 (SP263) Assay).

 

PD-L1 high was defined as >=25 percent of tumor cells (TC) or tumor-infiltrating immune cells (IC) expressing membrane PD-L1 if ICs involved >1 percent of the tumor area, or TC>=25 percent or IC=100 percent if ICs involved <=1 percent of the tumor area. Additionally, approximately 14.3 percent of all evaluable patients achieved partial response and 2.7 percent achieved complete response. Of patients who had received only neoadjuvant or adjuvant therapy prior to trial entry, 24 percent (n=9) responded. Based on a secondary endpoint in this single-arm trial, median time to response was 6 weeks. Among the total 31 responding patients, 14 patients (45%) had ongoing responses of 6 months or longer and five patients (16%) had ongoing responses of 12 months or longer.

 

Patients should be monitored for immune-mediated adverse reactions including pneumonitis, hepatitis, colitis, endocrinopathies (including adrenal insufficiency, hypophysitis, or type 1 diabetes mellitus), nephritis, rash, thrombocytopenic purpura, infection, infusion-related reactions, or embryo-fetal toxicity.