Christophe Massard, MD, PhD
The FDA approved the PD-L1 inhibitor durvalumab (Imfinzi) in May 2017 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.
, Christophe Massard, MD, PhD, medical oncologist, senior consultant of the Drug Development Department and Department of Medical Oncology, and chairman of the Early Drug Development Multidisciplinary Tumor Board, Gustave Roussy Institute, discussed the latest developments with durvalumab in urothelial carcinoma.
OncLive: Please provide some background on durvalumab leading up to its approval.
Durvalumab is a selective, high-affinity, engineered human IgG1 monoclonal antibody that blocks PD-L1 binding to PD-1 and CD80. An ongoing, multicenter, phase I/II open-label study (NCT1693562) is evaluating the safety and antitumor activity of durvalumab monotherapy in patients with advanced solid tumors, including locally advanced/metastatic urothelial carcinoma. An interim analysis of 61 patients with urothelial carcinoma in this study indicated that durvalumab was well tolerated and associated with antitumor activity, particularly in patients with PD-L1–high disease (≥25% of tumor cells or tumor-infiltrating immune cells express PD-L1), resulting in its breakthrough therapy designation by the FDA.
In [the] phase I/II open label study of locally advanced/metastatic urothelial carcinoma patients [that led to the approval of durvalumab, the treatment] was administered at 10 mg/kg every 2 weeks. Durvalumab showed favorable efficacy and an excellent safety profile in locally advanced/metastatic urothelial carcinoma patients.
What adverse events were seen with durvalumab on the trial?
Grade 3/4 treatment-related adverse events [AEs] occurred in less than 10% of patients. Grade 3/4 immune-mediated adverse events occurred in a minority of patients. Among patients with any-grade treatment-related AEs of special interest, patients received systemic steroids.
What advice do you have for community oncologists regarding serious or immune-related AEs?
Durvalumab, like other immune checkpoint blockers, generates atypical types of tumor responses—pseudoprogression, but also hyperprogression. Moreover, they have a specific toxicity profile that is challenging the historical oncologists’ practices, with the need to learn how to deal with the clinical management of immune-related AEs.
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