Adding atezolizumab to cabozantinib for the treatment of advanced renal cell carcinoma (RCC) that progressed on or after immune checkpoint inhibitor (ICI) therapy does not improve outcomes compared with cabozantinib alone, according to data presented at the ASCO Annual Meeting 2023.

Results from the phase 3 CONTACT-03 trial showed no significant difference in progression-free survival (PFS) between patients treated with the dual regimen and those treated with cabozantinib alone, said study presenter Toni K. Choueiri, MD, of the Dana-Farber Cancer Institute and Harvard Medical School in Boston.

In addition, he noted, the combination treatment led to increased toxicity, although the study did not reveal any specific safety signal. 

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The CONTACT-03 trial ( Identifier: NCT04338269) included 522 patients with locally advanced or metastatic RCC, regardless of PD-L1 status, that progressed on or after ICI treatment. CONTACT-03 is the first randomized, phase 3 trial to examine the efficacy and safety of a PD-L1 inhibitor after progression on or after prior PD-L1/PD-1 therapy, Dr Choueiri noted.

Enrolled patients were randomly assigned to receive atezolizumab at 1200 mg every 3 weeks in addition to cabozantinib at 60 mg daily (n=263) or to receive cabozantinib alone at 60 mg daily (n=259). Baseline characteristics were well balanced between the arms.

There was no significant difference in PFS or overall survival (OS) between the treatment arms. 

The median PFS was 10.6 months in the combination arm and 10.8 months in the monotherapy arm (stratified hazard ratio [sHR], 1.03; 95% CI, 0.83-1.28; P =.784). 

The median OS was 25.7 months in the combination arm and not reached in the monotherapy arm (sHR, 0.94; 95% CI, 0.70-1.27; P =.690).

Grade 3-4 adverse events (AEs) occurred in 67.6% of patients in the combination arm and 61.7% of those in the monotherapy arm. Grade 3-4 treatment-related AEs occurred in 55.3% and 47.3%, respectively. Serious treatment-related AEs occurred in 24.0% and 11.7%, respectively. 

AEs leading to treatment withdrawal occurred in 15.6% of patients in the combination arm and 3.9% in the monotherapy arm. There were 3 fatal treatment-related AEs in the combination arm. Fatal immune-mediated enterocolitis and renal failure were related to atezolizumab, and fatal intestinal perforation was related to cabozantinib.

“These data, in my opinion, and the opinion of the investigators, highlight the importance of randomized, prospective assessment of rechallenge with checkpoint inhibitors in RCC and potentially in other tumor types,” Dr Choueiri said.

Disclosures: This research was supported by F. Hoffmann La-Roche. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.


Choueiri T, Albiges L, Tomczak P, et al. Efficacy and safety of atezolizumab plus cabozantinib vs cabozantinib alone after progression with prior immune checkpoint inhibitor (ICI) treatment in metastatic renal cell carcinoma (RCC): Primary PFS analysis from the phase 3, randomized, open-label CONTACT-03 study. ASCO 2023, June 2-6, 2003. Abstract LBA4500.