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SAN FRANCISCO -- Treatment with pembrolizumab (Keytruda) induced complete responses in patients with non-muscle-invasive bladder cancer (NMIBC) who failed standard therapy, a phase II trial found.

In updated interim results from KEYNOTE-057, 40.2% of patients with disease that was unresponsive to bacillus Calmette-Guérin (BCG) achieved complete responses with the PD-1 inhibitor at 3 months (95% CI 30.6%-50.4%), reported Arjun Balar, MD, of Perlmutter Cancer Center at NYU Langone Health in New York City.

These responses appeared durable (median duration 12.7 months), and 75% of patients maintained this level of response at 6 months, but this percentage dropped to 53% at 9 months.

"Importantly, none of our patients who did not develop a response progressed to muscle-invasive disease," Balar said at the Genitourinary Cancers Symposium (GuCS) here.

He presented the results from cohort A of the KEYNOTE-057 study, which included patients with urothelial carcinoma in situ, with or without papillary disease.

The median follow-up among patients who achieved a complete response (primary endpoint) was 16.7 months. More than half (58.8%) of these patients had an ongoing response at the data cutoff, Balar noted. However, about one-third (36.6%) of complete responders subsequently experienced recurrent NMIBC.

Meeting attendee Seth Lerner, MD, of Baylor College of Medicine in Houston, commented by issuing a reminder that approval for BCG-unresponsive NMIBC requires not only meeting an initial rate of complete response, but showing durability at least to 12 months.

"It will be real important to get all of those patients out to 12 months with biopsies and cytology," Lerner said. "This data is preliminary and encouraging, but let's wait and see what happens."

Guru Sonpavde, MD, of the Dana-Farber Cancer Institute in Boston, agreed. "We still need to wait for more mature data from this to see how it pans out and whether the curve plateaus," he said.

Sonpavde noted that NMIBC is a very heterogeneous and unpredictable disease. "Given the variability of the natural history of the disease, it's a very challenging disease to study," he said. "And it's challenging to do big phase III studies."

The FDA has not approved a new agent for NMIBC since 1998, and from the agency for developing drugs in this setting note that "a high complete response rate is not meaningful if the response duration is short."

In 2015, an FDA advisory committee of Mycobacterium phlei cell wall-nucleic acid complex, following a phase II study of 129 patients where 22 achieved a complete response with the agent at 1 year. The 1-year disease-free survival rate in the study was 23.7%.

At the 2017 GuCS meeting, early data were presented on an interferon-based gene therapy in 40 patients with BCG-unresponsive high-grade NMIBC, and 35% of patients had recurrence-free survival at 1 year. That agent is currently in phase III development.

In the current study, 102 patients (median age 73) received 200-mg pembrolizumab every 3 weeks. An examination of subgroups in the trial showed that ethnicity may play a role in response, with 55.6% of non-white patients having a complete response versus 31.9% of whites. There were no correlations found between disease response and PD-L1 status or presence of papillary disease.

Balar noted that with just over 100 patients in the study, the researchers did not want to make too many inferences about the subgroups, and larger studies would provide more information on these trends.

The safety of pembrolizumab was similar to that seen in metastatic disease, Balar said. Only 8% of patients discontinued treatment because of adverse events (AEs). Only about 13% experienced a grade 3/4 AE and about 19% of patients experienced an immune-mediated AE. Although two deaths occurred, neither death was deemed relevant to treatment, he reported.

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