March 2016, Vol. 5, No. 2

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PD-L1 Inhibitor Has Strong Showing in Metastatic Urothelial Cancer

Genitourinary Cancers Symposium

Patients with previously treated metastatic urothelial cancer had response rates that exceeded historical standards when treated with an investigational immunotherapeutic agent, updated results from a large phase 2 study showed.

Treatment with the programmed death-1 ligand 1 (PD-L1) inhibitor atezolizumab led to an overall response rate of 15% in 311 patients, including 26% among patients who had the highest levels of PD-L1 expression. Historical data have demonstrated response rates of about 10% for second-line therapy and beyond. Responses, including complete responses, were observed across all categories of PD-L1 expression, prior number of therapies, and prior exposure to platinum-based chemotherapy.

Among responding patients, 84% of responses were ongoing at data cutoff, which occurred after a median follow-up of 11.7 months, Jean Hoffman-Censits, MD, reported at the Genitourinary Cancers Symposium.

“Given the current landscape of chemotherapy options for our patients with urothelial cancer progression following platinum chemotherapy, this primary analysis demonstrates that atezolizumab has the potential to change the standard of care for metastatic urothelial cancer,” said Hoffman-Censits, a medical oncologist at Kimmel Cancer Institute and Thomas Jefferson University in Philadelphia, PA.

The findings came from the phase 2 IMvigor 210 trial, an open-label evaluation of atezolizumab in patients, some of whom received the monoclonal antibody as their first therapy for metastatic disease.

Patients were not preselected by PD-L1 immune cell (IC) expression, which was assessed in all patients by immunohistochemistry. Assay results were categorized as IC0 (<1% expression), IC1 (1%-<5%), and IC2/3 (≥5%).

Three-fourths of the patients had received platinum-based chemotherapy, 81% had received prior systemic therapy for metastatic disease, 20% had received 2 prior regimens for metastatic disease, and 21% had received 3 or more prior regimens in the metastatic setting.

Hoffman-Censits reported that 26% of patients with IC2/3 expression had objective responses to treatment with atezolizumab. The overall response rate declined to 18% for an analysis of IC1/2/3 expression. She said 8% of patients with IC0 expression status responded to atezolizumab.

Overall, almost half of all patients had some degree of tumor reduction in response to atezolizumab. Duration of response ranged from 2.0 to 13.7 months, and the median duration of response had yet to be reached for any IC subgroup.

A substantial proportion of patients achieved stable disease with atezolizumab, said Hoffman-Censits. The disease control rate (response plus stable disease for at least 24 weeks) was 35% in the IC2/3 group, 21% in the IC1 group, and 19% in the IC0 group.

Subgroup analysis showed response rates of 20% for patients who had received 4 or more prior regimens for metastatic urothelial cancer, 33% in patients with nodal metastases only, 14% in patients with ECOG 1 performance status, and 21% in patients with baseline hemoglobin values less than 10 g/dL.

The median progression-free survival was 2.1 months and did not differ between patients with IC2/3 and IC1 expression levels for PD-L1. Overall survival was 11.4 months for the IC2/3 group, 6.7 months for the IC0/1 group, and 7.9 months for all 311 patients. The 12-month overall survival was 48% for IC2/3, 30% for IC0/1, and 36% overall.

“Considering that the 12-month overall survival estimates for patients receiving second-line chemotherapy are about 20%, these data are truly exciting,” said Hoffman-Censits.

The most common treatment-related adverse events were fatigue (30%; 2% grade 3/4), nausea (14%; 0% grade 3/4), decreased appetite (12%; 1% grade 3/4), and pruritus (10%; less than 1% grade 3/4). Hoffman-Censits said 5% of patients had grade 3/4 immune-mediated adverse events (any type).

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