ESMO 2021: Cabozantinib-Nivolumab Versus Nivolumab-Cabozantinib in Patients With Metastatic Clear Cell RCC Following One Prior VEGFR TKI: The CABIR Multicenter Matching-Adjusted Study

( The European Society of Medical Oncology (ESMO) 2021 virtual annual meeting’s non-prostate cancer session included a presentation by Dr. Yann Vano discussing the CABIR study of patients receiving cabozantinib-nivolumab versus nivolumab-cabozantinib after receiving a prior VEGFR TKI for metastatic clear cell RCC. Nivolumab and cabozantinib are two approved agents after a prior TKI in metastatic RCC patients. However, the optimal sequence, cabozantinib-nivolumab or nivolumab-cabozantinib, is still unknown. The superiority of cabozantinib over everolimus in patients with prior anti-PD-1 (HR 0.22, 95% CI 0.07-0.65) in the METEOR trial suggests a sensitizing role of nivolumab.1 At the 2021 ESMO congress, Dr. Vano and colleagues presented results of the CABIR study to identify the optimal sequence between cabozantinib-nivolumab and nivolumab-cabozantinib after one prior TKI.


 In this multicenter retrospective study, data was collected from patients receiving cabozantinib-nivolumab or nivolumab-cabozantinib, after first-line TKI. A propensity score was calculated to handle bias selection, and sequence comparisons were carried out with a Cox model on a matched sample 1:1. A weighted 1:2 matching and a cox model with propensity score as adjusting covariate were also performed as sensibility analysis. The primary endpoint was progression-free survival (PFS) from the start of second-line therapy to progression in third-line (PFS2/3) therapy. The secondary endpoint was overall survival from second-line (OS2) therapy.  

 Among the 139 patients in this study, 38 (27%) and 101 (73%) patients received cabozantinib-nivolumab and nivolumab-cabozantinib, respectively. Median follow-up from the initiation of the second-line was 24.1 months for nivolumab-cabozantinib and 19.7 months for cabozantinib-nivolumab. Overlap in propensity score allowed 1:1 matching of all cabozantinib-nivolumab patients, with patient’s characteristics being well balanced. For PFS2/3, nivolumab-cabozantinib was superior to cabozantinib-nivolumab (HR 0.58, 95% CI 0.34-0.98):




Additionally, for OS2 (HR 0.66, 95% CI 0.42-1.05), nivolumab-cabozantinib trended towards a survival benefit over cabozantinib-nivolumab. Considering PFS2 and PFS3 separately, the only significant difference was in PFS3 in favor of cabozantinib over nivolumab (p=0.0012). This difference was solely driven by patients previously treated with 6 to 18 months of first-line TKI. Interaction between sequence and first-line duration was significant in the matched cohort. The results regarding ORR mirrored the PFS trends with similar response rates in the 2nd and 3rd line (11% and 21%, respectively) with nivolumab while response rates with cabozantinib improved when given after nivolumab (53% versus 21%):




Dr. Vano concluded this presentation of the CABIR study with the following summary statements:

  • This study, using a matching-adjusted comparison, showed a prolonged OS and PFS with nivolumab-cabozantinib sequence compared to cabozantinib-nivolumab in metastatic RCC patients treated with 6 to 18 months of prior TKI
  • Cabozantinib efficacy after nivolumab in third-line seems to drive this nivolumab-cabozantinib superiority strengthening the hypothesis of a sensitizing role of anti-PD-1 on TKI efficacy


Presented by: Yann Vano, MD, Medical Oncology, Hôpital Européen Georges Pompidou, APHP.Centre–Université de Paris, Paris, France

Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Assistant Professor of Urology, Georgia Cancer Center, Augusta University/Medical College of Georgia, @zklaassen_md on Twitter during the 2021 European Society for Medical Oncology (ESMO) Annual Congress 2021, Thursday, Sep 16, 2021 – Tuesday, Sep 21, 2021.


  1. Choueiri TK, Escudier B, Powles T, et al. Cabozantinib versus Everolimus in Advanced Renal-Cell Carcinoma. N Engl J Med 2015;373(19):1814-1823.