Padcev, Keytruda Combination Proves Impactful for Patients with Metastatic Urothelial Cancer

Durability results of Padcev (enfortumab vedotin) plus Keytruda (pembrolizumab) for locally advanced or metastatic urothelial carcinoma showed a 73% response rate among patients on a phase 2 trial with 86% of patients alive in the one year follow up, according to results presented at the American Society of Clinical Oncology (ASCO) Genitourinary Cancers Symposium.

Padcev — an antibody-drug conjugate (ADC) targeting the nectin-4 gene that is found in 95% of bladder cancer tumors – was granted accelerated approval by the Food and Drug Administration as it filled an unmet need for patients with locally advanced or metastatic urothelial carcinoma. Researchers believed that Padcev along with Keytruda, however, could show an even greater benefit for treating patients with metastatic urothelial carcinoma, which resulted in the EV-103 study.

The phase 2 trial has shown promise for this patient group reaching 12.3 months of progression free survival where either drug alone did not, according to Dr. Jonathan Rosenberg.

Rosenberg, chief of genitourinary medical oncology services at Memorial Sloan Kettering Cancer Center in New York, New York, presented updated findings for this study at the ASCO Genitourinary Cancers Symposium. Rosenberg sat down with CURE® to discuss some of the side effects of the combination therapy and how he thinks it is already making an impact for patients.

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So, it's being used widely and in the right patients, on patients who are refractory to immunotherapy and platinum chemotherapy. There are patients, though, who can't get immunotherapy for autoimmunity, for example, or people who are not really candidates for platinum.

I think some physicians are testing out how to use these drugs in those special patient populations, but it's clearly having an impact, I think we're going to see a lot of use of this medicine.

The rash is probably the most common side effect that will impact management in the short term, because it tends to occur early in the first few weeks. And over time, peripheral neuropathy becomes more of a problem as you might expect with a cytotoxic with that side effect profile. If you're on it for a long time, you're more likely to get it.

It usually also responds to holding the dose for a period of time letting the toxicity get better and then resuming it at a lower dose. I think physicians will need to understand the nuances of some of these aspects of treatment as time goes on in order to optimally deploy the drug in their patients.