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 |
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Authors: | 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 David F. McDermott |
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Affiliation: | 1. Barts Cancer Institute, Queen Mary University of London, London, UK;2. Georgetown Lombardi Comprehensive Cancer Center, Washington, DC, USA;3. Gustave Roussy, Villejuif, France;4. Memorial Sloan Kettering Cancer Center, New York, NY, USA;5. Vanderbilt University Medical Center, Nashville, TN, USA;6. University of California, San Francisco, School of Medicine, San Francisco, CA, USA;7. Mayo Clinic Hospital, Jacksonville, FL, USA;8. City of Hope Comprehensive Cancer Center, Duarte, CA, USA;9. Yale School of Medicine, New Haven, CT, USA;10. Sarah Cannon Research Institute, Nashville, TN, USA;11. The University of Chicago Medicine, Chicago, IL, USA;12. Texas Oncology-Baylor Charles A. Sammons Cancer Center, Dallas, TX, USA;13. CHU Hopitaux de Bordeaux, Hôpital Saint-André, Bordeaux, France;14. Azienda Ospedaliera S. Maria, Terni, Italy;15. Vall d’Hebron Institute of Oncology, Vall d’Hebron University Hospital, Universitat Autònoma de Barcelona, Barcelona, Spain;p. Dana-Farber Cancer Institute, Boston, MA, USA;q. Florida Cancer Specialists & Research Institute, Fort Myers, FL, USA;r. Rocky Mountain Cancer Center, Denver, CO, USA;s. Genentech, Inc., South San Francisco, CA, USA;t. Roche Products Ltd, Welwyn Garden City, UK;u. Beth Israel Deaconess Medical Center, Boston, MA, USA |
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Abstract: | BackgroundThe 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.ObjectiveTo evaluate the efficacy and safety of atezolizumab + bevacizumab following disease progression on atezolizumab or sunitinib monotherapy in patients with mRCC.Design, setting, and participantsIMmotion150 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.InterventionPatients 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 analysisThe 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 limitationsFifty-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.ConclusionsThe 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 summaryPatients 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. |
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Keywords: | Atezolizumab Bevacizumab Cancer immunotherapy Metastatic Renal cell carcinoma Second line Sunitinib Vascular endothelial growth factor inhibitor |
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