Efficacy

Tecentriq (Atezolizumab) Efficacy in Urothelial Carcinoma

Tecentriq (atezolizumab) is an immune checkpoint inhibitor specifically designed to target and bind to the PD-L1 protein expressed on tumor cells and tumor-infiltrating immune cells, blocking its interactions with PD-1 and B7.1 receptors. By inhibiting PD-L1, Tecentriq may enable the activation of T cells, which can then affect the immune-mediated killing of tumor cells. In the context of urothelial carcinoma, the efficacy of Tecentriq has been evaluated in several clinical trials. The drug has shown promise in both locally advanced and metastatic urothelial carcinoma, particularly in patients who have disease progression during or following platinum-containing chemotherapy or within 12 months of neoadjuvant or adjuvant chemotherapy.

In a pivotal phase 3 study (IMvigor211), Tecentriq did not meet its primary endpoint of improved overall survival in the overall patient population. However, in a pre-specified subgroup analysis of patients with high levels of PD-L1 expression, there was an observed survival benefit. The results indicated that patient selection based on PD-L1 expression could be crucial for achieving the best outcomes with Tecentriq in urothelial carcinoma. The FDA has approved Tecentriq for the treatment of patients with locally advanced or metastatic urothelial carcinoma who are not eligible for cisplatin-containing chemotherapy and for patients who have disease progression during or following any platinum-containing chemotherapy, or within 12 months of neoadjuvant or adjuvant chemotherapy.

Padcev (Enfortumab Vedotin-ejfv) Efficacy in Urothelial Carcinoma

Padcev (enfortumab vedotin-ejfv) is an antibody-drug conjugate that targets Nectin-4, a protein found on the surface of cells and highly expressed in urothelial carcinoma. The drug is composed of an anti-Nectin-4 monoclonal antibody linked to a microtubule-disrupting agent, monomethyl auristatin E (MMAE). Upon binding to Nectin-4-expressing cells, Padcev is internalized and releases MMAE, leading to cell cycle arrest and apoptotic cell death. The efficacy of Padcev has been demonstrated in a phase 2 clinical trial (EV-201) in patients with locally advanced or metastatic urothelial cancer who had previously received a PD-1 or PD-L1 inhibitor and a platinum-based chemotherapy. The results showed a significant proportion of patients achieved an objective response, with some experiencing complete responses.

Based on the findings from the EV-201 trial, the FDA granted accelerated approval to Padcev for the treatment of adult patients with locally advanced or metastatic urothelial cancer who have previously received a PD-1 or PD-L1 inhibitor and a platinum-containing chemotherapy in the neoadjuvant/adjuvant, locally advanced or metastatic setting. The accelerated approval was contingent upon the verification and description of clinical benefit in confirmatory trials. Subsequent trials, including the phase 3 EV-301 trial, have continued to evaluate the efficacy and safety of Padcev in urothelial carcinoma, further supporting its use in this patient population.