Urothelial carcinoma (UC) is the most common type of bladder cancer, accounting for approximately 90% of bladder cancer cases. Nearly half of patients with advanced UC are ineligible for cisplatin-based chemotherapy, often resulting in limited treatment options and a poor prognosis. Recently, the U.S. FDA approved an expanded indication for the ADC drug Padcev: for the treatment of adult patients with locally advanced or metastatic UC who are ineligible for cisplatin-based chemotherapy and have received one or more prior lines of therapy.
Padcev international research data changed Padcev from accelerated approval to routine approval, and the approval of Padcev for expanded indications was based on 2 supplementary biological product license applications (sBLA). These sblas were approved under the U.S. FDA's real-Time Oncology review (RTOR) pilot project.
The sBLA supporting the routine approval of Padcev is based on data from the global phase 3 EV-301 confirmatory trial. This trial was conducted in adult patients with locally advanced or metastatic urothelial carcinoma who had previously received platinum-based chemotherapy and a PD-1/L1 inhibitor, comparing Padcev to chemotherapy. Results showed that, with a median follow-up of 11.1 months, the Padcev group had significantly longer overall survival (median OS: 12.88 months vs 8.97 months; HR=0.70; 95% CI: 0.56, 0.89; p=0.001) and significantly longer progression-free survival (median PFS: 5.55 months vs 3.71 months; HR=0.62, 0.001) compared to the chemotherapy group.
With the transition of Padcev from accelerated approval to routine approval, when treating advanced UC patients who have received platinum-containing chemotherapy and immunotherapy in the past, clinicians now have for the first time a treatment method that has been proven to have a total survival (OS) advantage over chemotherapy.
The sBLA supporting the expansion of Padcev's indications is based on the results of the pivotal phase 2 EV-201 trial, column 2. Column 2 was conducted in patients with locally advanced or metastatic urothelial carcinoma who had previously received one PD-1/L1 inhibitor, had not received platinum-based chemotherapy, and were ineligible for cisplatin-based chemotherapy. Results showed that after a median follow-up of 16 months, the confirmed objective response rate (ORR) in patients treated with Padcev was 51% (95% CI: 39.8, 61.3), with a complete response rate (CR) of 20%; the median duration of response (mDOR) was 10.9 months; the median progression-free survival (mPFS) and median overall survival (mOS) were 5.8 months and 14.7 months, respectively.
Padcev drug introduction
Drug name: Enfortumab vedotin
Product name: Padcev
Manufacturer: Astellas Pharma
Consultant: United Cancer Centre of Hong Kong
Padcev is a first-in-class antibody-drug conjugate (ADC) targeting a cell surface protein highly expressed in bladder cancer. The drug is composed of enfortumab, a human IgG1 monoclonal antibody targeting Nectin-4, conjugated to the cytotoxic agent MMAE (monomethyl auristatin E, a microtubule disruptor). Nectin-4 is a therapeutic target highly expressed in various solid tumors, including urothelial carcinoma. In December 2019, Padcev received accelerated approval from the U.S. FDA for the treatment of patients with locally advanced or metastatic urothelial carcinoma.
Warm reminder: Padcev is the first ADC drug approved for the treatment of urothelial cancer, and it is also the first drug approved for patients with locally advanced or metastatic UC who have previously received platinum-containing chemotherapy and a PD-1 or PD-L1 inhibitor.
