Padcev Combination Shows Promise in Patients with Metastatic Bladder Cancer

The combination use of Padcev (enfortumab vedotin) plus Keytruda (pembrolizumab) induced a high rate of durable objective response rates (ORR) in patients with locally advanced or metastatic urothelial cancer who were ineligible for cisplatin-based chemotherapy, according to updated results from the phase 1b/2 EV-103 trial presented during the 2020 Genitourinary Cancers Symposium.

“While platinum chemotherapy is the standard treatment for patients with metastatic urothelial carcinoma, some patients are not eligible for treatment with cisplatin,” according to a press release, issued by the American Society of Clinical Oncology (ASCO).

“Gemcitabine/carboplatin is poorly tolerated, and survival and durability of response are limited.”

Padcev, an antibody-drug conjugate, works by disrupting the formation and function of microtubules, to certain cells that are highly expressed in urothelial carcinoma.

Therefore, Dr. Jonathan E. Rosenberg and colleagues conducted the ongoing, multi-cohort, open-label, multicenter — designed to evaluate the efficacy and safety of the combination in 45 patients with locally advanced or metastatic urothelial carcinoma who were ineligible for platinum-based treatment. Patients received 1.25 mg/kg of Padcev in combination with Keytruda.

Safety and tolerability served as the study’s primary endpoint. Secondary endpoints included ORR, disease control rate, duration of response, progression-free survival (the time from treatment to disease progression or worsening), and overall survival.

The most common treatment-emergent side effects were fatigue (58%), alopecia (53%) and peripheral sensory neuropathy (53%). One patient died due to a side effect reported as related to treatment (multiple organ failure).

At a median follow-up of 11.5 months, patients demonstrated an ORR of 73%, which included a 15.6% complete response rate and a 57.8% partial response rate.

Progression-free survival was 12.3 months, and overall survival at one year was 81.6%. Median duration of response has not been reached.

“The results compare favorably to historical data with gemcitabine and carboplatin chemotherapy,” the release said.

Further findings showed that 55% of the 33 responses were ongoing at the time of the analysis, with 83.9% of responses lasting six months or more and 53.7% of responses lasting 12 months or more.

"Cisplatin-based chemotherapy is the standard treatment for first-line advanced urothelial cancer; however, it isn't an option for many patients," Rosenberg, medical oncologist and chief of genitourinary medical oncology service at Memorial Sloan Kettering Cancer Center in New York City, said in a press release. "I'm encouraged by these interim results, including a median progression-free survival of a year for patients who received the platinum-free combination of Padcev and pembrolizumab in the first-line setting."

Additional urothelial cancer cohorts of EV-103 will evaluate Padcev for the following indications:

• alone or in combination with Keytruda or platinum-based chemotherapy in the first-line setting for patients with metastatic disease;
• plus Keytruda and carboplatin or cisplatin in first-line metastatic disease;
• alone or in combination with Keytruda in muscle-invasive disease;
• in combination with Keytruda in second-line metastatic disease;
• plus gemcitabine in first- or second-line metastatic disease.

In December 2019, the Food and Drug Administration granted accelerated approval to Padcev for the treatment of adult patients with locally advanced or metastatic urothelial cancer who have received prior treatment with a PD-1/PD-L1 inhibitor and platinum-containing chemotherapy.