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.
To evaluate the efficacy and safety of atezolizumab + bevacizumab following disease progression on atezolizumab or sunitinib monotherapy in patients with mRCC.
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.
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.
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.
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.
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.
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.
European urology. 2021 Mar 04 [Epub ahead of print]
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 Leng, Kenji Hashimoto, Mahrukh Huseni, Christina Schiff, David F McDermott
Barts Cancer Institute, Queen Mary University of London, London, UK. Electronic address: ., Georgetown Lombardi Comprehensive Cancer Center, Washington, DC, USA., Gustave Roussy, Villejuif, France., Memorial Sloan Kettering Cancer Center, New York, NY, USA., Vanderbilt University Medical Center, Nashville, TN, USA., University of California, San Francisco, School of Medicine, San Francisco, CA, USA., Mayo Clinic Hospital, Jacksonville, FL, USA., City of Hope Comprehensive Cancer Center, Duarte, CA, USA., Yale School of Medicine, New Haven, CT, USA., Sarah Cannon Research Institute, Nashville, TN, USA., The University of Chicago Medicine, Chicago, IL, USA., Texas Oncology-Baylor Charles A. Sammons Cancer Center, Dallas, TX, USA., CHU Hopitaux de Bordeaux, Hôpital Saint-André, Bordeaux, France., Azienda Ospedaliera S. Maria, Terni, Italy., Vall d'Hebron Institute of Oncology, Vall d'Hebron University Hospital, Universitat Autònoma de Barcelona, Barcelona, Spain., Dana-Farber Cancer Institute, Boston, MA, USA., Florida Cancer Specialists & Research Institute, Fort Myers, FL, USA., Rocky Mountain Cancer Center, Denver, CO, USA., Genentech, Inc., South San Francisco, CA, USA., Roche Products Ltd, Welwyn Garden City, UK., Beth Israel Deaconess Medical Center, Boston, MA, USA.