Atezolizumab may benefit some patients with metastatic urothelial carcinoma, high PD-L1 expression
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SAN FRANCISCO — Atezolizumab monotherapy improved OS compared with chemotherapy among patients with PD-L1-high, cisplatin-ineligible metastatic urothelial carcinoma, according to an exploratory analysis of a randomized phase 3 study.
Atezolizumab (Tecentriq, Genentech) also appeared better tolerated than chemotherapy, findings presented at ASCO Genitourinary Cancers Symposium showed.
The exploratory analysis came from the IMvigor130 study, which assessed three regimens — atezolizumab plus platinum-based chemotherapy, atezolizumab monotherapy, or placebo plus platinum-based chemotherapy — as first-line therapy for treatment-naive advanced bladder cancer.
As Healio previously reported, the study failed to achieve one of its key endpoints, as researchers observed no OS benefit with the addition of atezolizumab to chemotherapy. That finding prompted atezolizumab’s manufacturer last year to voluntarily withdraw the agent’s indication in the U.S. for treatment of locally advanced or metastatic urothelial carcinoma.
“There has been a lot of subanalysis and also a lot of translational research, so there is more to come from this study beyond the fact that, regulatory-wise, it was a negative study,” Aristotelis Bamias, MD, associate professor at the Medical School at University of Athens, Greece, told Healio. “I still believe that the results of this study — although exploratory, unfortunately — point out that there is a role for immunotherapy in first-line treatment for cisplatin-ineligible, PD-L1 positive patients.”
Background and methodology
Atezolizumab — an anti-PD-L1 antibody — is approved in the United States for treatment of certain patients with lung cancer, liver cancer or melanoma.
The FDA had granted accelerated approval to the agent for treatment of patients with locally advanced or metastatic urothelial carcinoma who were ineligible for cisplatin-containing chemotherapy and whose tumors express PD-L1, or those ineligible for platinum-containing chemotherapy regardless of PD-L1 status.
The randomized phase 3 IMvigor130 trial — conducted as part of postmarketing requirements to convert the accelerated approval to regular approval — assessed the addition of atezolizumab to platinum-based chemotherapy as first-line therapy for treatment-naive advanced bladder cancer.
Researchers enrolled 1,213 adults with locally advanced or metastatic urothelial cancer treated across 221 sites in 35 countries.
Galsky and colleagues randomly assigned patients to atezolizumab plus platinum-based chemotherapy (group A; n = 451), atezolizumab monotherapy (group B; n = 362) or placebo plus platinum-based chemotherapy (group C; n = 400).
Chemotherapy consisted of IV gemcitabine dosed at 1,000 mg/m² on days 1 and 8 of each 21-day cycle plus either IV carboplatin area under the curve 4.5 mg/mL per min or IV cisplatin 70 mg/m² on day 1 of each cycle. Patients in group A and group B received IV atezolizumab dosed at 1,200 mg on day 1 of each cycle.
Investigator-assessed PFS and OS served as co-primary endpoints.
Results
In the intention-to-treat population, results showed a numerical improvement in OS with atezolizumab monotherapy vs. placebo-chemotherapy, but the difference did not reach statistical significance (median, 15.2 months vs. 13.3 months; HR = 0.98; 95% CI, 0.82=1.16).
Exploratory analyses assessed outcomes based on percentage of PD-L1-positive immune cells, including less than 1% (IC0), 1% to less than 5% (IC1), or 5% or higher (IC2/3).
Researchers reported numerical improvements in OS with atezolizumab monotherapy vs. placebo-chemotherapy among all patients classified as PD-L1 IC2/IC3 cohort, but the difference did not reach statistical significance (median, 27.5 months vs. 16.7 months; HR = 0.7; 95% CI, 0.48-1.03).
However, among cisplatin-ineligible patients classified as PD-L1 IC2/IC3, researchers reported a statistically significant OS benefit with atezolizumab monotherapy (18.6 months vs. 10 months; HR = 0.56; 95% CI, 0.34-0.91).
Researchers reported no OS benefit with atezolizumab monotherapy among patients classified as PD-L1 IC0/IC1.
A higher percentage of patients assigned placebo-chemotherapy than atezolizumab monotherapy experienced grade 3/grade 4 treatment-related adverse events (80% vs. 16%). Three patients (1%) in the atezolizumab monotherapy group and four (1%) in the placebo-chemotherapy group experienced grade 5 treatment-related adverse events.
Next steps
More data — particularly from patients with earlier-stage disease — are needed to confirm the potential benefit of atezolizumab monotherapy for patients with cisplatin-ineligible metastatic urothelial carcinoma and high PD-L1 expression, Bamias said.
“Everybody who works on immunotherapy is trying these agents in earlier stages of the disease ... [and] we need to wait for these results,” Bamias told Healio. “It doesn’t mean that because immunotherapy is such a good therapy for metastatic disease that it will benefit patients in earlier stages, so we need to wait to see the conclusive results from these studies.”
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Bamias A, et al. Abstract LBA441. Presented at: ASCO Genitourinary Cancers Symposium; Feb. 16-18, 2023: San Francisco.
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