Atezolizumab, a PD-L1 Inhibitor, Shows Impressive Results in Metastatic Urothelial Cancer

Charles Bankhead

March 2016, Vol 7, No 2 - Emerging Therapies


Patients with previously treated metastatic urothelial cancer had response rates that exceeded historical standards when treated with an investigational immunotherapeutic agent, updated results of a large phase 2 clinical trial showed. Treatment with the PD-1 ligand 1 (PD-L1) inhibitor atezolizumab led to an overall response rate of 15% in 311 patients, including a 26% rate 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 reported across all categories of PD-L1 expression, previous number of therapies, and previous exposure to platinum-based chemotherapy. At data cutoff after a median follow-up of 11.7 months, 84% of the responses among responding patients were still ongoing, said Jean H. Hoffman-Censits, MD, Director, Multidisciplinary Genitourinary Oncology Center, Thomas Jefferson University Hospitals, Philadelphia, PA, at the 2016 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,” Dr Hoffman-Censits said.

Study Details

The findings came from the phase 2 IMvigor 210 clinical trial, an open-label study of atezolizumab in patients with locally advanced or metastatic urothelial cancer, some of whom received the monoclonal antibody atezolizumab as their first therapy for metastatic disease. Many patients had a poor prognosis.

Patients were not preselected by PD-­L1 immune-cell (IC) expression, which was assessed by immunohistochemistry. Assay results were categorized as IC0 (<1% expression), IC1 (1%-<5%), and IC2/3 (?5%). Most patients had tumors that demonstrated PD-L1 expression.

Overall, 75% of patients had received platinum-based chemotherapy, 81% had received previous systemic therapy for metastatic disease, 20% had received 2 previous regimens, and 21% had received ?3 previous regimens.

Dr Hoffman-Censits reported that 26% of patients with IC2/3 expression had objective responses to atezolizu­mab. The overall response rate declined to 18% for patients with IC1/2/3 expression. In addition, 8% of patients with IC0 expression status responded to atezolizumab.

Exciting Results

Overall, almost 50% 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 has yet to be reached by any subgroup.

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

Subgroup analysis showed response rates of 20% for patients who had received ?4 previous regimens for metastatic urothelial cancer; 17% for those with visceral metastases; 11% in visceral metastases; 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 subgroup, 6.7 months for the IC0/1 subgroup, 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 Dr Hoffman-Censits.

The most common treatment-related adverse events were fatigue (30%, 2% grade 3/4), nausea (14%), decreased appetite (12%, 1% grade 3/4), and pruritus (10%, <1% grade 3/4).

Dr Hoffman-Censits said 5% of patients had grade 3 or 4 immune-mediated adverse events of any type.

A phase 3, randomized clinical trial with atezolizumab, IMvigor 211, is currently under way.