Atezolizumab added to cabozantinib does not improve clinical outcomes in patients with metastatic renal cell carcinoma

1. Progression-free and overall survival was comparable in both the intervention and control groups.

2. Serious adverse events were more common among patients taking a combination of atezolizumab-cabozantinib than cabozantinib-only.

Evidence Rating Level: 1 (Excellent)

Study Rundown: Immune checkpoint inhibitors are first-line therapy for patients with metastatic renal cell carcinoma (MRCC); however, optimal management for patients with disease progression following therapy remains unknown. This randomized controlled trial aimed to assess whether the addition of atezolizumab to cabozantinib could delay disease progression and improve survival in patients with MRCC refractory to immune checkpoint inhibitor treatment. The primary outcome was progression-free survival, while a key secondary outcome was overall survival. According to study results, the addition of atezolizumab to cabozantinib did not improve clinical outcomes and instead, resulted in increased toxicity. This study was limited by a lack of statistical significance which may deter the use of immune checkpoint inhibitors outside of the clinical trial in this population.

Click to read the study in The Lancet

Relevant Reading: Lenvatinib plus Pembrolizumab or Everolimus for Advanced Renal Cell Carcinoma

In-depth [randomized-controlled trial]: Between Jul 28, 2020, and Dec 27, 2021, 692 patients were screened for eligibility across 135 study sites in 15 countries. Included were patients ≥ 18 years old with locally advanced or metastatic renal cell carcinoma (MRCC) refractory to immune checkpoint inhibitor treatment. Altogether, 522 patients (263 in atezolizumab-cabozantinib group and 259 in cabozantinib-only group) were included in the final analysis. The primary outcome of progression-free survival was comparable in both groups (10.6 months, 95% confidence interval [CI] 9.8-12.3 in atezolizumab-cabozantinib vs. 10.8 months, 95% CI 10.0-12.5 in cabozantinib-only, hazard ratio [HR] 1.03, p=0.78). This was true for the secondary outcome concerning median overall survival (25.7 months in the atezolizumab-cabozantinib group and was not evaluable in the cabozantinib monotherapy group; p=0.69). Serious adverse events were more common in the atezolizumab-cabozantinib (48%) than cabozantinib-only (33%) but deaths related to adverse events were similar between groups (6% vs. 4%, respectively). Overall, findings from this study suggest that adding atezolizumab to cabozantinib does not improve clinical outcomes and may increase toxicity in patients with renal cell carcinoma.

Image: PD

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