Padcev With or Without Keytruda Elicits Responses in Urothelial Cancer

Among patients with metastatic urothelial carcinoma — a form of bladder cancer — treatment with Padcev (enfortumab vedotin) plus Keytruda (pembrolizumab) was found to elicit responses in the first-line setting, while Padcev showed clinical benefit in later lines of therapy, according to researchers.

Utilizing data from three randomized clinical trials and eight nonrandomized prospective studies published between 2019 and 2024 that included 2,128 patients, researchers published their findings in JAMA Network Open. Of these patients, 563 (26.5%) received Padcev plus Keytruda, 814 (38.3%) received Padcev monotherapy and 751 (35.3%) received chemotherapy.

Investigators found that Padcev plus Keytruda was associated with a pooled disease control rate (DCR) of 86%, an objective response rate (ORR) of 68% and a one-year survival rate of 79%, while Padcev monotherapy had a pooled DCR of 73%, an ORR of 43% and a one-year survival rate of 52%. Furthermore, a network meta-analysis showed that Padcev plus Keytruda had a 3.47 times higher chance of eliciting a response compared with chemotherapy. Moreover, the combination was associated with a 2.32 times higher chance of survival at one year compared to chemotherapy.

Researchers noted that of the data they drew from, all Padcev plus Keytruda studies (three in total) were as first-line treatments, while all Padcev monotherapy studies (seven in total) were second-line or later treatments.

“The findings demonstrate that [Padcev], both as monotherapy and in combination with [Keytruda], offers substantial clinical benefits compared with conventional chemotherapy,” Dr. Shugo Yajima and colleagues wrote in their findings. “[Padcev] plus [Keytruda] had an ORR of 68% and DCR of 86%, surpassing historical benchmarks for [metastatic urothelial carcinoma] treatments. These results represent a substantial leap forward in the management of this disease. Similarly, [Padcev] monotherapy was associated with higher response rates compared with chemotherapy, particularly in later lines of treatment.”

Regarding safety, while Padcev monotherapy and Padcev plus Keytruda had numerically lower odds of high-grade side effects when compared with chemotherapy (28% lower and 17% lower, respectively), the differences were not statistically significant.

More Information on Padcev and Keytruda

Padcev is a type of targeted therapy known as an antibody-drug conjugate. Antibody-drug conjugates, as defined by the National Cancer Institute, consist of a monoclonal antibody chemically linked to a cancer-killing drug; the monoclonal antibody binds to a protein on the surface of a cancer cell, and the drug enters the cell and kills it.

Keytruda, a type of immunotherapy drug known as an immune checkpoint inhibitor, binds to the protein PD-1 on the surface of immune cells called T cells to keep cancer cells from suppressing the immune system, the National Cancer Institute explains.

The U.S. Food and Drug Administration (FDA) approved the combination of Padcev and Keytruda for patients with locally advanced or metastatic bladder cancer in December 2023, less than a year after the agency granted the drug combination accelerated approval for patients who were ineligible for cisplatin-based chemotherapy treatment.

“[Padcev] really made an evolution, if you will, in the urothelial or bladder cancer world,” Dr. Yousef Zakharia told CURE last year. He is a medical oncologist and vice-chair of the Genitourinary Malignancy Disease Group, as well as lead of the Kidney Cancer Program, at the Mayo Clinic Comprehensive Cancer Center, in Phoenix, Arizona. He also serves as the medical director of the Experimental Therapeutics Clinic at Mayo Clinic AZ.

“In this meta-analysis of 11 studies, [Padcev]–based therapy was associated with favorable outcomes in [metastatic urothelial carcinoma] treatment settings,” Yajima and colleagues wrote in the study. “[Padcev] plus [Keytruda] was associated with higher response rates in the first-line setting, while [Padcev] monotherapy was associated with clinical benefit in later lines. The distinct profiles of these regimens underscore the importance of personalized treatment approaches. Ongoing research is crucial to further refine [Padcecv]–based therapies and improve outcomes for [patients with metastatic urothelial carcinoma].”

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