Enfortumab vedotin plus pembrolizumab induces durable responses in metastatic urothelial carcinoma
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The combination of enfortumab vedotin and pembrolizumab conferred high rates of durable responses among cisplatin-ineligible patients with metastatic urothelial carcinoma, according to results of the multicohort EV-103 study.
“This combination is quite effective compared with the standard of care, which generally is not very effective,” Jonathan E. Rosenberg, MD, chief of the genitourinary medical oncology service in the division of solid tumor oncology at Memorial Sloan Kettering Cancer Center, told HemOnc Today. “The safety profile seems similar to what you would see with either drug by itself, so I think it’s acceptable overall.”
Platinum chemotherapy remains the standard first-line treatment for patients with metastatic urothelial carcinoma. Those ineligible for cisplatin receive gemcitabine and carboplatin as a standard therapy; however, this chemotherapy regimen has poor tolerability, as well as limited durability and survival benefit.
Enfortumab vedotin (ASG-22ME, Seattle Genetics), an antibody-drug conjugate that delivers the microtubule-disrupting agent MMAE to cells expressing nectin-4, has been shown to induce antitumor activity in previously treated metastatic urothelial carcinoma.
Rosenberg and colleagues analyzed the efficacy and safety of enfortumab vedotin in combination with the anti-PD-1 therapy pembrolizumab (Keytruda, Merck) among 45 patients (median age, 69 years; range, 51-90) with metastatic urothelial carcinoma.
Patients received 1.25 mg/kg enfortumab vedotin on days 1 and 8 and pembrolizumab on day 1 of each 3-week treatment cycle (median number of cycles, 9; range, 1-22).
Safety and tolerability served as the study’s primary endpoints. Objective response rate, PFS and determination of recommended enfortumab vedotin dose served as secondary endpoints.
Median follow-up was 11.5 months.
The most common treatment-related adverse events included fatigue, experienced by 58% of patients (11% grade 3), alopecia (53%) and peripheral sensory neuropathy (53%; 4% grade 3).
“Neuropathy can be a problem over time for many of these patients,” Rosenberg said. “It’s almost the price of success, because you have to be on it long enough for it to be a problem. There are times where it doesn’t get better or go away, but those [cases] are generally the exceptions.”
One patient died of treatment-related organ failure.
Efficacy results showed an ORR of 73.3% (95% CI, 58.1-85.4), including a 15.6% complete response rate. Researchers reported an overall disease control rate of 93.3%.
More than half of patients with liver metastasis (53%; n = 8) responded to treatment. Patients with high PD-L1 status (n = 14) had an ORR of 78.6%, whereas those with low PD-L1 status (n = 19) had an ORR of 63.2%.
“What was notable in this trial was that patients with PD-L1-positive and -negative statuses responded at essentially the same rate,” Rosenberg said. “[Although] pembrolizumab works nicely in metastatic bladder cancer in certain patients, it’s not a home run. This clearly added to the activity of pembrolizumab in this disease.”
Among the 33 responders, 18 (55%) have ongoing responses, 11 of which exceeded 10 months.
Median duration of response was not reached (range, 1.2-12.9 months). Median PFS was 12.3 months (95% CI, 7.98-not reached).
“The response rate of this level with this degree of durability is unprecedented in urothelial cancer,” Rosenberg said. “There is a phase 3 trial that will be launching to further study this.” – by John DeRosier
Reference:
Rosenberg JE, et al. Abstract 441.
Disclosures: Rosenberg reports consultant/advisory roles with Merck and Seattle Genetics, and research funding to his institution from Seattle Genetics and other pharmaceutical companies. Please see the abstract for a full list of Rosenberg’s and all other authors’ relevant financial disclosures.
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