Efficacy and Safety of Atezolizumab Plus Bevacizumab Following Disease Progression on Atezolizumab or Sunitinib Monotherapy in Patients with Metastatic Renal Cell Carcinoma in IMmotion150: A Randomized Phase 2 Clinical Trial

Thomas Powles, Michael B. Atkins, Bernard Escudier, Robert J. Motzer, Brian I. Rini, Lawrence Fong, Richard W. Joseph, Sumanta K. Pal, Mario Sznol, John Hainsworth, Walter M. Stadler, Thomas E. Hutson, Alain Ravaud, Sergio Bracarda, Cristina Suarez, Toni K. Choueiri, James Reeves, Allen Cohn, Beiying Ding, Ning LengKenji Hashimoto, Mahrukh Huseni, Christina Schiff, David F. McDermott

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Background: The use of immune checkpoint inhibitors combined with vascular endothelial growth factor (VEGF)-targeted therapy as second-line treatment for metastatic clear cell renal cancer (mRCC) has not been evaluated prospectively. Objective: To evaluate the efficacy and safety of atezolizumab + bevacizumab following disease progression on atezolizumab or sunitinib monotherapy in patients with mRCC. Design, setting, and participants: IMmotion150 was a multicenter, randomized, open-label, phase 2 study of patients with untreated mRCC. Patients randomized to the atezolizumab or sunitinib arm who had investigator-assessed progression as per RECIST 1.1 could be treated with second-line atezolizumab + bevacizumab. Intervention: Patients received atezolizumab 1200 mg intravenously (IV) plus bevacizumab 15 mg/kg IV every 3 wk following disease progression on either atezolizumab or sunitinib monotherapy. Outcome measurements and statistical analysis: The secondary endpoints analyzed during the second-line part of IMmotion150 included objective response rate (ORR), progression-free survival (PFS), and safety. PFS was examined using Kaplan-Meier methods. Results and limitations: Fifty-nine patients in the atezolizumab arm and 78 in the sunitinib arm were eligible, and 103 initiated second-line atezolizumab + bevacizumab (atezolizumab arm, n = 44; sunitinib arm, n = 59). ORR (95% confidence interval [CI]) was 27% (19–37%). The median PFS (95% CI) from the start of second line was 8.7 (5.6–13.7) mo. The median event follow-up duration was 19.4 (12.9–21.9) mo among the 25 patients without a PFS event. Eighty-six (83%) patients had treatment-related adverse events; 31 of 103 (30%) had grade 3/4 events. Limitations were the small sample size and selection for progressors. Conclusions: The atezolizumab + bevacizumab combination had activity and was tolerable in patients with progression on atezolizumab or sunitinib. Further studies are needed to investigate sequencing strategies in mRCC. Patient summary: Patients with advanced kidney cancer whose disease had worsened during treatment with atezolizumab or sunitinib began second-line treatment with atezolizumab + bevacizumab. Tumors shrank in more than one-quarter of patients treated with this combination, and side effects were manageable. Patients with metastatic renal clear cell carcinoma whose disease progressed on atezolizumab or sunitinib monotherapy were treated with atezolizumab plus bevacizumab. Anti–vascular endothelial growth factor (VEGF) therapy with cancer immunotherapy demonstrated efficacy after failure of immune checkpoint or VEGF receptor inhibitor therapy.

Original languageEnglish (US)
JournalEuropean urology
DOIs
StateAccepted/In press - 2021

Keywords

  • Atezolizumab
  • Bevacizumab
  • Cancer immunotherapy
  • Metastatic
  • Renal cell carcinoma
  • Second line
  • Sunitinib
  • Vascular endothelial growth factor inhibitor

ASJC Scopus subject areas

  • Urology

Fingerprint Dive into the research topics of 'Efficacy and Safety of Atezolizumab Plus Bevacizumab Following Disease Progression on Atezolizumab or Sunitinib Monotherapy in Patients with Metastatic Renal Cell Carcinoma in IMmotion150: A Randomized Phase 2 Clinical Trial'. Together they form a unique fingerprint.

Cite this