In the phase III CONTACT-03 trial reported in The Lancet, Sumanta Pal, MD, FASCO, and colleagues found that the addition of atezolizumab to cabozantinib did not improve outcomes in patients with renal cell carcinoma whose disease progressed on or after prior immune checkpoint inhibitor treatment.

Study Details

In the open-label trial, 522 patients with locally advanced or metastatic disease from sites in 15 countries in Asia, Europe, North America, and South America were randomly assigned between July 2020 and December 2021 to receive atezolizumab at 1,200 mg every 3 weeks plus cabozantinib at 60 mg once daily (n = 263) or cabozantinib alone (n = 259). Overall, 77% of patients were male and 83% were White. The most commonly received previous systemic treatments were ipilimumab/nivolumab in the first line and single-agent nivolumab in the second line. The primary endpoints were progression-free survival on blinded independent central review and overall survival in the intent-to-treat population.

The addition of atezolizumab to cabozantinib did not improve clinical outcomes and led to increased toxicity. These results should discourage sequential use of immune checkpoint inhibitors in patients with renal cell carcinoma outside of clinical trials.

— Sumanta Pal, MD, FASCO, and colleagues

Tweet this quote

Progression-Free and Overall Survival

At data cutoff in January 2023, median follow-up was 15.2 months (interquartile range = 10.7–19.3 months). Median progression-free survival was 10.6 months (95% confidence interval [CI] = 9.8–12.3 months) in the atezolizumab/cabozantinib group vs 10.8 months (95% CI = 10.0–12.5 months) in the cabozantinib group (hazard ratio [HR] = 1.03, 95% CI = 0.83–1.28, P = .78); rates at 1 year were 44% vs 48%. Median overall survival was 25.7 months (95% CI = 21.5 months to not evaluable) in the atezolizumab/cabozantinib group vs not evaluable (95% CI = 21.1 months to not evaluable) in the cabozantinib group (HR = 0.94, 95% CI = 0.70–1.27, P = .69); rates at 1 year were 79% vs 76%.  

An objective response was achieved in 41% vs 41% of patients. Median response duration was 12.7 months (95% CI = 10.5–17.4 months) vs 14.8 months (95% CI = 11.3–20.0 months).

Adverse Events

The most common adverse events of any grade in both the atezolizumab/cabozantinib group and cabozantinib group were diarrhea (65% vs 71%), palmar-plantar erythrodysesthesia syndrome (39% vs 41%), decreased appetite (38% vs 38%), and hypothyroidism (36% vs 38%). Grade 3 or 4 adverse events occurred in 68% vs 62% of patients. Serious adverse events occurred in 48% vs 33%, most commonly pulmonary embolism (4%) and pyrexia (3%) in the atezolizumab/cabozantinib group, and pulmonary embolism (2%) in the cabozantinib group. Adverse events led to discontinuation of any study treatment in 16% vs 4% of patients. Treatment-related death occurred in three patients in the atezolizumab/cabozantinib group, due to renal failure, enterocolitis, and gastrointestinal perforation, respectively, and in no patients in the cabozantinib group.

The investigators concluded, “The addition of atezolizumab to cabozantinib did not improve clinical outcomes and led to increased toxicity. These results should discourage sequential use of immune checkpoint inhibitors in patients with renal cell carcinoma outside of clinical trials.”

Toni K. Choueiri, MD, of the Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, is the corresponding author for The Lancet article. 

Disclosure: The study was funded by F. Hoffmann-La Roche and Exelixis. For full disclosures of the study authors, visit thelancet.com.