Atezolizumab/Bevacizumab Demonstrates Comparable OS to Sunitinib for Metastatic RCC

The final analysis of the phase 3 IMmotion151 trial did not reveal a significant improvement in overall survival with atezolizumab plus bevacizumab over sunitinib for previously untreated patients with metastatic renal cell carcinoma.

Atezolizumab (Tecentriq) plus bevacizumab (Avastin) demonstrated comparable overall survival (OS) to sunitinib (Sutent) for patients with metastatic renal cell carcinoma (mRCC), according to the final analysis of the phase 3 IMmotion151 trial (NCT02420821), although the primary end point of progression-free survival (PFS) was met at the interim analysis.

In the intention-to-treat (ITT) population, the median OS was 36.1 months (95% CI, 31.5-42.3) for patients in the atezolizumab arm compared with 35.3 months (95% CI, 28.6-42.1) for patients in in the sunitinib arm (HR, 0.91; 95% CI, 0.76-1.08). The median OS for the PD-L1–positive patients was 38.7 months (95% CI, 29.0-49.7) and 31.6 months (95% CI, 23.3-42.1) for the atezolizumab sunitinib arms, respectively (HR, 0.85; 95% CI, 0.64-1.13).

“Although the combination of atezolizumab plus bevacizumab showed a PFS benefit versus sunitinib, the final analysis from the IMmotion151 study did not demonstrate improved OS for patients with mRCC in the ITT or [PD-L1–positive] populations,” the investigators wrote. “The final safety analysis was consistent with previously reported safety profiles of atezolizumab plus bevacizumab in mRCC.”

Patients with measurable mRCC, and tumor tissue available for PD-L1 testing were eligible for the IMmotion151 trial. Atezolizumab was administered intravenously at 1200 mg and bevacizumab was given intravenously at 15 mg/kg every 3 weeks. Sunitinib was administered orally at 50 mg once daily.

A total of 915 patients were assessed in the study’s final analysis, with a mean age of 62.0 years in the atezolizumab group and 60.0 years in the sunitinib group. Overall, most patients were male (73.1%). For patients eligible for the safety analysis, the median duration of treatment was 12.7 months for patients receiving atezolizumab, 11.8 months for bevacizumab, and 9.2 months for sunitinib.

Adverse effects (AEs) of any grade were observed in 98% of patients eligible for safety analysis in the atezolizumab group and 99% of patients in the sunitinib group. AEs leading to study treatment withdrawal were seen in 28% and 12% of patients in the atezolizumab and sunitinib groups, respectively.

In the atezolizumab arm, grade 3 or 4 AEs were seen in 46% of patients, with proteinuria (8%) reported as the most common grade 3 or 4 AE.

“While the combination of atezolizumab plus bevacizumab did not show improved OS vs sunitinib, the biomarker analyses provide insight into the molecular basis of differential survival outcomes and inform development of personalized approaches for treatment with antiangiogenics, checkpoint inhibitors, and their combinations in mRCC,” the investigators concluded.

Reference

Motzer RJ, Powles T, Atkins MB, et al. Final overall survival and molecular analysis in IMmotion151, a phase 3 trial comparing atezolizumab plus bevacizumab vs sunitinib in patients with previously untreated metastatic renal cell carcinoma. JAMA Oncol. Published online January 23, 2021. doi:10.1001/jamaoncol.2021.5981