Atezolizumab Could Be Start of “Seismic Shift” in Treatment of Metastatic Urothelial Cancer

ASCO

Atezolizumab has clinically meaningful activity as primary therapy in patients with cisplatin-ineligible locally advanced/metastatic urothelial cancer, according to data from the IMvigor 210 study.

Preliminary results also showed encouraging overall survival (OS) data, said Arjun V. Balar, MD, Codirector of the Genitourinary Cancers Program, New York University Langone Medical Center, New York City.

Based on the results from IMvigor 210, “I think these data make a compelling argument for atezolizumab to be a potential new standard of care in patients with cisplatin-ineligible metastatic urothelial cancer,” he remarked. “Moreover, it could represent the beginning of a seismic shift in our treatment approach for all patients with metastatic disease, irrespective of their eligibility for cisplatin.”

In May 2016, the FDA approved atezolizumab in the second-line setting (after failure of platinum-based chemotherapy) for the treatment of patients with locally advanced or metastatic urothelial carcinoma.

Cisplatin-based chemotherapy is currently the standard of care in the first-line setting, but many patients with metastatic urothelial cancer are ineligible for cisplatin because of poor performance status or impaired renal function and are instead treated with noncisplatin-based regimens or best supportive care, said Dr Balar. But response durations are short with noncisplatin-based regimens.

Atezolizumab is a humanized engineered monoclonal antibody that selectively targets PD-L1 (programmed death-1 [PD-1] ligand 1). By inhibiting its interactions with receptors PD-1 and B7-1, “it can reinvigorate exhausted T cells and unleash antitumor immunity,” he said.

Data from cohort 1 of IMvigor 210 were presented here; this cohort included 119 cisplatin-ineligible chemotherapy-naive patients (median age, 73 years) in the metastatic setting. The bladder/urethra was the primary tumor site in 71% of the patients. Two-thirds had metastatic disease at visceral sites. Renal impairment was the most common contraindication to cisplatin. Atezolizumab 1200 mg was administered intravenously every 3 weeks until disease progression.

At the time of data cutoff in March 2016, 98 patients had discontinued treatment, the most common reason being disease progression (75 patients).

With a median duration of follow-up of 14.4 months, the objective response rate (ORR) was 24%, and 7% achieved a complete response (CR). Similar responses were observed when response rates were stratified by PD-L1 expression. Most notably, the ORR was 21% and the CR rate was 8% in the PD-L1 underexpressing subgroup, said Dr Balar. “Across the board, we see complete responses in all IC [immune cell] subgroups,” he said. “Activity of this level in this patient population is unprecedented.”

He continued, “Responses were rapid, at a median time of 2.1 months…and they are durable.” The median duration of response was not yet reached in any predefined PD-L1 subgroup. Seventy-five percent of the responses are ongoing.

Meaningful tumor regression was observed across all IC subgroups, including 63% of patients with IC scored as 0.

On subgroup analysis, patients with upper tract disease had a 42% ORR, compared with 17% in patients whose primary tumor site was the bladder or urethra. Patients with only lymph node metastases had a 32% ORR compared with 15% in those with visceral sites of metastatic disease.

The estimated median OS for the entire study population was 14.8 months, and the estimated 12-month OS rate was 57%. Median OS was consistent across the IC subgroups.

Atezolizumab was generally well tolerated; only 6% discontinued treatment due to an adverse event. Treatment-related all-grade and grade 3/4 adverse events occurred in 66% and 15% of patients, respectively. Treatment-related all-grade adverse events with a frequency ≥10% included fatigue (30%), pruritus (11%), and diarrhea (11%). One patient died of sepsis.

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