Image: Pexels | Written by: Medical Companion Travel Content Team
Original articles, please do not reprint without permission
Urothelial carcinoma is the most common type of bladder cancer, accounting for about 90% of all bladder cancer patients. Padcev (enfortumab vedotin-ejfv) is the first drug to go beyond chemotherapy and immunotherapy, with significant therapeutic effects in the treatment of locally advanced or metastatic urothelial cancer. In 2019, Padcev was officially approved for marketing in the United States, becoming the world's first ADC drug for the treatment of urinary tract carcinoma. What's so amazing about Padcev? Let's take a closer look.
First, about urinary urothelial cancer
Bladder cancer is a disease in which cancer cells form in the tissues of the bladder, and urothelial cancer is the most common type of bladder cancer, accounting for about 90% of all cases of bladder cancer. Urinary intestinal carcinoma ranks fourth in the incidence of male tumors, the overall number of patients in the mainland is second only to the United States in the world, and the number of people under 65 years old accounts for 40%, and there is a trend of rejuvenation.
Second, the mechanism of action and efficacy of Padcev (enfortumab vedotin-ejfv).
Padcev (enfortumab vedotin-ejfv) is an ADC that targets Nectin-4, an adhesion protein located on the surface of most urothelial cancer cells. It consists of a complete human IgG1-kappa antibody that binds to the microtubule destroyer MMAE by protease-lysable ligation.
Non-clinical data suggest that padcev's anticancer activity is due to ADC binding to cells expressing Nectin-4, followed by internalization of the ADC-Nectin-4 complex, and MMAE released by proteolytic cleavage. The release of MMAE disrupts the microtubule network within the cell, which subsequently induces cell cycle arrest and apoptotic cell death.
The disease control rate is as high as 93.3%, and Padcev is effective in treating patients with urinary tract carcinoma who have received chemotherapy
For patients with metastatic advanced urothelial cancer, platinum chemotherapy is the preferred treatment criterion. However, for patients who are not eligible for platinum therapy, although gemcitabine plus carboplatin can be used as an alternative, the therapeutic effect of this regimen is not satisfactory.
The 2020 American Society of Clinical Oncology Symposium on Genitourinary Cancer published data from the Phase IB/II clinical trial EV-103 evaluating the safety and efficacy of Padcev immunotherapy.
The EV-103 trial included a total of 45 patients with locally advanced or metastatic urothelial carcinoma who were not eligible for cisplatin-based chemotherapy regimens (median age 69 years), after an average of nine courses of Combined Immunotherapy with Padcev+Keytruda.
The results of the trial showed that the median objective response rate (ORR) confirmed by padcev+Keytruda immunotherapy at 11.5 months was 73.3%, the effective rate was 73%, the complete response rate was 15.6%, the partial response rate (PR) was 57.8%, and the disease control rate was as high as 93.3%. Progression-free survival was 12.3 months and an overall 1-year survival rate was 81.6%.
So far, the safety and efficacy of Padcev immunotherapy have been verified.
Padcev (enfortumab vedotin-ejfv) is about to be approved in the Eu
In January 2022, Astella and Seattle Genetics jointly announced that the European Medicines Agency's Commission on Pharmaceutical Products for Human Use issued a review recommending the approval of Padcev as a monotherapy for the treatment of adult patients with locally advanced or metastatic urothelial cancer who had previously received platinum-containing chemotherapy and PD-1/PD-L1 inhibitors.
Padcev (enfortumab vedotin-ejfv) was approved for historical review
In December 2019, Padcev received accelerated FDA approval for the treatment of patients with locally advanced or metastatic urothelial cancer. Prior to this, the FDA had granted Padcev a breakthrough drug to treat the above-mentioned UC patients.
In January 2020, Padcev was approved for the treatment of recurrent bladder cancer.
In March 2021, Padcev applied for marketing in Japan for the treatment of refractory patients with PD-(L)1 inhibitors. In May of the same year. Japan's Ministry of Health, Labor and Welfare granted priority review qualifications for new drug applications submitted by Astyspic Group.
In July 2021, the FDA granted Padcev expanded indications for the treatment of adult patients with locally advanced or metastatic urothelial carcinoma (UC) who are not eligible for cisplatin chemotherapy and who have previously received first- or multiple-line therapy.
5. Conclusion
It is reported that almost half of patients with advanced urinary urothelial cancer are not eligible for cisplatin-based chemotherapy. The FDA's approval of Padcev to expand the indications is an important clinical advance in the treatment of urinary urothelial cancer. Unfortunately, Padcev has not yet been listed in China, and domestic urinary tract cancer patients can obtain it through the regular overseas medical platform (medical companion travel) if necessary. The author also expects Padcev to be listed in China as soon as possible to facilitate the use of drugs for domestic urinary tract cancer patients.