Atezolizumab, With or Without Chemo, Did Not Improve OS in Advanced Urothelial Cancer

Neither atezolizumab plus chemotherapy nor atezolizumab alone improved overall survival (OS) when compared to chemotherapy alone in patients with locally advanced or metastatic urothelial cancer in the phase 3 IMvigor130 trial.^1,2 These results, from the final OS analysis, were reported in 2 papers published in The Lancet Oncology.  

The IMvigor130 trial (Clinical Trials Identifier: NCT02807636) included 1213 adults with locally advanced or metastatic urothelial cancer who had not received systemic treatment in the metastatic setting.

The patients were randomly assigned to receive atezolizumab plus platinum-based chemotherapy, atezolizumab alone, or platinum-based chemotherapy alone. Chemotherapy consisted of gemcitabine and either carboplatin or cisplatin. Across the treatment arms, baseline characteristics were generally similar.

Atezolizumab Plus Chemo vs Chemo Alone

In one analysis, researchers compared final OS results with atezolizumab plus chemotherapy (n=451) to final OS results with chemotherapy alone (n=400).¹ The median follow-up was 13.4 months.

The median OS was 16.1 months in the atezolizumab-chemotherapy arm and 13.4 months in the chemotherapy-alone arm (stratified hazard ratio [HR], 0.85; 95% CI, 0.73-1.00; P =.023). This did not cross the prespecified boundary for statistical significance (P =.021).

The 1-year OS rate was 60% in the atezolizumab-chemotherapy arm and 55% in the chemotherapy-alone arm. The 2-year OS rate was 38% and 32%, respectively. The 3-year OS rate was 26% and 22%, respectively.

The safety population included 454 patients who received atezolizumab plus chemotherapy and 389 patients who received chemotherapy alone. Treatment-related adverse events (TRAEs) occurred in 96% of patients in both arms.

The rate of grade 3-4 TRAEs was 81% in the atezolizumab-chemotherapy arm and 80% in the chemotherapy-alone arm. The most common grade 3-4 TRAEs were anemia (37% and 34%, respectively), neutropenia (37% vs 30%), decreased neutrophil count (22% vs 24%), thrombocytopenia (21% vs 18%), and decreased platelet count (20% vs 24%).

Fatal TRAEs occurred in 9 patients in the atezolizumab-chemotherapy arm (acute kidney injury, dyspnea, hepatic failure, hepatitis, neutropenia, pneumonitis, respiratory failure, sepsis, and thrombocytopenia). Fatal TRAEs also occurred in 4 patients in the chemotherapy-alone arm (unexplained death, diarrhea, febrile neutropenia, and toxic hepatitis).

Atezolizumab Alone vs Chemotherapy Alone

In a second analysis, researchers compared final OS results in 360 patients who received atezolizumab monotherapy to final OS results in 359 patients who received chemotherapy alone.²

At a median follow-up of 13.4 months, the median OS was not significantly different between the atezolizumab and chemotherapy arms — 15.2 months and 13.3 months, respectively (stratified HR, 0.98; 95% CI, 0.82-1.16).

However, among patients who were ineligible for cisplatin and had high PD-L1 expression, the median OS was longer with atezolizumab than with chemotherapy — 18.6 months and 10.0 months, respectively (unstratified HR, 0.56; 95% CI, 0.34-0.91).

In the overall cohort, the 1-year OS rate was 57.9% in the atezolizumab arm and 54.6% in the chemotherapy arm. The 2-year OS rate was 34.5% and 32.3%, respectively. The 3-year OS rate was 27.0% and 21.8%, respectively.

The safety population included 354 patients who received atezolizumab monotherapy and 389 who received chemotherapy alone. TRAEs occurred in 61% of patients in the atezolizumab arm and 96% of those in the chemotherapy arm.

The rate of grade 3-4 TRAEs was 16% in the atezolizumab arm and 80% in the chemotherapy arm. The most common grade 3-4 TRAEs were anemia (1% and 34%, respectively), neutropenia (<1% vs 30%), decreased neutrophil count (0% vs 24%), and decreased platelet count (<1% vs 24%). The most common grade 3-4 TRAE in the atezolizumab arm was asthenia (1% vs 4%).

There were 3 fatal TRAEs in the atezolizumab arm (pneumonia, interstitial lung disease, and large intestinal obstruction), and there were 4 fatal TRAEs in the chemotherapy arm (diarrhea, febrile neutropenia, unexplained death, and toxic hepatitis).

“These exploratory findings from IMvigor130 suggest that atezolizumab monotherapy might be an effective alternative to carboplatin-based chemotherapy for a subset of patients with high PD-L1-expressing locally advanced or metastatic urothelial carcinoma who are ineligible for standard first-line cisplatin-based chemotherapy, particularly given its more favorable safety profile,” the researchers wrote.

Disclosures: This study was sponsored by F. Hoffmann-La Roche. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original references for complete disclosures.

This article originally appeared on Cancer Therapy Advisor