September 23, 2023

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Padcev: Bladder cancer is expected to usher in new therapies

Padcev: Bladder cancer is expected to usher in new therapies.



Padcev: Bladder cancer is expected to usher in new therapies.  The new antibody conjugate Padcev brings surprises! Bladder cancer is expected to usher in new therapies.

Bladder cancer is the 10th most common cancer in the world, and urothelial cancer is the most common type of bladder cancer.

Recently, the US FDA approved two supplementary biological license applications (sBLA) for the antibody-conjugated drug Padcev (Enfortumab Vedotin), and granted priority approval for the treatment of patients with locally advanced or metastatic urothelial cancer.




▌The new dawn of treatment for patients with bladder cancer


Urothelial carcinoma (UC) is the most common type of bladder cancer, accounting for approximately 90% of all bladder cancers. Bladder cancer is the tenth most common cancer in the world. In 2020, there will be over 570,000 newly diagnosed cases of bladder cancer, and about 200,000 people will die from the disease worldwide.

Currently, platinum-containing chemotherapy is the first-line standard treatment for patients with advanced UC. Most patients with advanced UC can benefit from initial therapy, and the disease control rate can reach 70% after first-line platinum chemotherapy.

Nevertheless, some patients have disease progression within 9 months after chemotherapy. After chemotherapy fails, about 80% of advanced patients do not respond to PD-1 or PD-L1 inhibitor treatment, and it is difficult for second-line therapy to meet clinical treatment standards.

Previously, the antibody conjugate Trodelvy was approved for the treatment of UC, bringing new hopes for treatment to patients with recurrence and metastasis.

However, due to the continuous increase in newly diagnosed cases of urothelial cancer, the prognosis has not changed much, and the patient’s survival period has been greatly shortened. Therefore, more effective programs are needed to treat bladder cancer.




▌Antibody conjugate drug: Padcev

Padcev: Bladder cancer is expected to usher in new therapies


Padcev is an antibody-drug conjugate (ADC) that targets a cell surface protein that is highly expressed in bladder cancer. The drug is composed of Enfortumab, a human IgG1 monoclonal antibody targeting Nectin-4 (Nectin-4), coupled with a microtubule disrupting agent MMAE (monomethyl auristatin E).

Nectin-4 is a membrane protein that is overexpressed in a variety of tumor cells, such as urothelial cancer, breast cancer, pancreatic cancer, and bladder cancer. Therefore, the protein has become a popular therapeutic target.

At the end of 2019, Padcev received accelerated approval from the FDA for the treatment of adult patients with locally advanced or metastatic urothelial cancer. These patients have previously received PD-1/L1 inhibitor treatment or received one before/after surgery. Kind of platinum-containing chemotherapy.

It is worth mentioning that Padcev is the world’s first ADC drug approved for the treatment of UC.

Previously, the drug was used in combination with “K drug” pembrolizumab, and positive results were achieved in clinical trials. The patient’s objective response rate reached 73.3%; the median progression-free survival (PFS) was 12.3 months; the one-year survival period was 81.6%. I look forward to further positive data from this trial, and strive to make the immune combination therapy approved for marketing as soon as possible.




▌Significantly improved prognosis, two studies bring surprises!

This priority review is based on the results of the EV-201 and EV-301 trials.

Padcev: Bladder cancer is expected to usher in new therapies
The ongoing Phase 2 EV-201 trial enrolls 219 patients, with an estimated completion date of May 2025. The main result of this trial is the objective response rate (ORR). Secondary results include duration of response (DOR), disease control rate (DCR) at 16 weeks, progression-free survival (PFS), overall survival (OS), and adverse events (AEs). Currently, 91 patients have participated in the study, of which 89 patients have received treatment.

In the interim analysis, the ORR of patients in the treatment group was 52%, including a CR of 20%.

At a median treatment time of 6 months, the patient’s median OS and PFS were 5.8 months.

EV-301 is a larger study with 608 participants. The primary endpoint of the prospective study is OS. Secondary results include PFS, ORR, DCR, AEs and DOR.

Among them, 301 patients received Padcev treatment, and 307 patients received chemotherapy. The median follow-up time was 11.1 months.

In the interim analysis, the OS of the treatment group was 12.88 months, while that of the chemotherapy group was 8.97 months (HR=0.70). At the same time, the PFS of the treatment group was better than that of the chemotherapy group (5.55 months VS 3.71 months, HR=0.62).

In addition, the positive results of these trials are expected to transform Padcev from accelerated approval to regular approval. And in both studies, it was found that the drug can significantly improve the prognosis of patients. It is expected that the drug will be fully approved as soon as possible and benefit more patients with urothelial cancer.





▌Real case: Third-degree cancer and recurrence of urothelial cancer, Harvard experts overseas help

A 51-year-old patient with recurrent urothelial cancer. Her condition is very special: she had received a kidney transplantation due to uremia before, and then successively found breast cancer and breast cancer lung metastases. Two years ago, she was diagnosed with invasive high-grade urothelial carcinoma, and her condition was under control after chemotherapy. But at the beginning of this year, urothelial cancer recurred and metastasized.

In order to find a better treatment plan, she held a face-to-face meeting with Professor Marc D. Michaelson, the clinical director of the Urogenital Cancer Center of Massachusetts General Hospital and an expert on urogenital cancer at Harvard Medical School. “Video consultation.

Professor Michaelson gave specific medication recommendations and precautions on chemotherapy, targeted therapy, and immunotherapy options.

He also specifically introduced a viable new therapy-antibody-conjugated drug (ADC). For example, the Nectin-targeting antibody conjugate Padcev mentioned in the article has been approved by the US FDA at the end of 2019 for use in metastatic urothelial cancer after chemotherapy and immunotherapy have failed. If conditions permit, a clinical trial of another antibody conjugate targeting Trop-2, Trodelvy (Sacituzumab Govitecan), can also be considered (not yet approved at that time). The advice of American experts pointed out a new direction for Ms. Zhang’s treatment.

At present, only a small percentage of patients can benefit from chemotherapy or immunotherapy for a long time, but for patients with advanced urothelial cancer who are still progressing after first-line and second-line treatment, treatment options are very limited. The approval of more antibody-conjugated drugs has brought new treatment options for such refractory patients.




(source:internet, reference only)

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