Immunotherapy Combo Fails to Improve Overall Survival in Advanced Kidney Cancer

By Reuters Staff

December 28, 2021

NEW YORK (Reuters Health) - In previously untreated metastatic renal-cell cancer (mRCC), upfront treatment with the anti-PD-L1 immune-checkpoint inhibitor atezolizumab plus the anti-vascular endothelial growth factor (VEGF) agent bevacizumab did not improve overall survival (OS) compared to standard treatment with sunitinib in the IMmotion151 study.

However, findings from an exploratory subanalysis suggest that biomarker analyses may identify patients who could benefit from combined anti-PD-L1 and anti-VEGF therapy, the research team says in JAMA Oncology.

In the IMmotion151 study, 915 patients with previously untreated mRCC were randomly assigned to atezolizumab (1,200 mg) plus bevacizumab (15 mg/kg) given intravenously every three weeks or oral sunitinib (50 mg/day for four weeks, followed by two weeks off treatment). Patients were stratified by PD-L1 status.

At the interim analysis, the atezolizumab/bevacizumab combination had a favorable safety profile and was associated with prolonged progression-free survival (PFS). At the time, OS results were immature.

In the final analysis, there was no significant difference in OS between patients receiving atezolizumab plus bevacizumab and those on standard sunitinib (median OS, 36.1 vs. 35.3 months) or in the PD-L1+ populations (38.7 vs. 31.6 months), report Dr. Robert Motzer of Memorial Sloan Kettering Cancer Center in New York and colleagues.

However, they say the exploratory outcome of atezolizumab plus bevacizumab versus sunitinib showed "improved median OS trends in patients whose tumors were characterized by T-effector/proliferative, proliferative, or small nucleolar RNA transcriptomic profiles" (35.4 vs. 21.2 months; hazard ratio, 0.70; 95% CI, 0.50 to 0.98).

"Although the biomarker results were promising, further evaluation and validation of these molecular subsets in additional datasets are required to inform applicability to other anti-angiogenesis plus checkpoint inhibitor combinations, to other clinical settings, such as in adjuvant therapy, and to add value to existing clinical risk group models," the researchers caution.

The study was sponsored by F. Hoffmann-La Roche Ltd. and Genentech, Inc. Dr. Motzer has financial relationships with Genentech/Roche and other pharmaceutical companies.

SOURCE: JAMA Oncology, online December 23, 2021