Thomas Powles1, Michael B Atkins2, Bernard Escudier3, Robert J Motzer4, Brian I Rini5, Lawrence Fong6, Richard W Joseph7, Sumanta K Pal8, Mario Sznol9, John Hainsworth10, Walter M Stadler11, Thomas E Hutson12, Alain Ravaud13, Sergio Bracarda14, Cristina Suarez15, Toni K Choueiri16, James Reeves17, Allen Cohn18, Beiying Ding19, Ning Leng19, Kenji Hashimoto20, Mahrukh Huseni19, Christina Schiff19, David F McDermott21. 1. Barts Cancer Institute, Queen Mary University of London, London, UK. Electronic address: Thomas.Powles@bartshealth.nhs.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. 16. Dana-Farber Cancer Institute, Boston, MA, USA. 17. Florida Cancer Specialists & Research Institute, Fort Myers, FL, USA. 18. Rocky Mountain Cancer Center, Denver, CO, USA. 19. Genentech, Inc., South San Francisco, CA, USA. 20. Roche Products Ltd, Welwyn Garden City, UK. 21. Beth Israel Deaconess Medical Center, Boston, MA, USA.
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.
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.
Authors: Chung-Han Lee; Andreas M Hötker; Martin H Voss; Darren R Feldman; Kaitlin M Woo; Sujata Patil; Devyn T Coskey; Oguz Akin; James J Hsieh; Robert J Motzer Journal: Clin Genitourin Cancer Date: 2015-08-07 Impact factor: 2.872
Authors: David F McDermott; Jeffrey A Sosman; Mario Sznol; Christophe Massard; Michael S Gordon; Omid Hamid; John D Powderly; Jeffrey R Infante; Marcella Fassò; Yan V Wang; Wei Zou; Priti S Hegde; Gregg D Fine; Thomas Powles Journal: J Clin Oncol Date: 2016-01-11 Impact factor: 44.544
Authors: Roy S Herbst; Jean-Charles Soria; Marcin Kowanetz; Gregg D Fine; Omid Hamid; Michael S Gordon; Jeffery A Sosman; David F McDermott; John D Powderly; Scott N Gettinger; Holbrook E K Kohrt; Leora Horn; Donald P Lawrence; Sandra Rost; Maya Leabman; Yuanyuan Xiao; Ahmad Mokatrin; Hartmut Koeppen; Priti S Hegde; Ira Mellman; Daniel S Chen; F Stephen Hodi Journal: Nature Date: 2014-11-27 Impact factor: 49.962
Authors: James D Turnbull; Julien Cobert; Tracy Jaffe; Michael R Harrison; Daniel J George; Andrew J Armstrong Journal: Clin Genitourin Cancer Date: 2012-10-04 Impact factor: 2.872
Authors: Robert J Motzer; Bernard Escudier; David F McDermott; Saby George; Hans J Hammers; Sandhya Srinivas; Scott S Tykodi; Jeffrey A Sosman; Giuseppe Procopio; Elizabeth R Plimack; Daniel Castellano; Toni K Choueiri; Howard Gurney; Frede Donskov; Petri Bono; John Wagstaff; Thomas C Gauler; Takeshi Ueda; Yoshihiko Tomita; Fabio A Schutz; Christian Kollmannsberger; James Larkin; Alain Ravaud; Jason S Simon; Li-An Xu; Ian M Waxman; Padmanee Sharma Journal: N Engl J Med Date: 2015-09-25 Impact factor: 91.245
Authors: David F McDermott; Mahrukh A Huseni; Michael B Atkins; Robert J Motzer; Brian I Rini; Bernard Escudier; Lawrence Fong; Richard W Joseph; Sumanta K Pal; James A Reeves; Mario Sznol; John Hainsworth; W Kimryn Rathmell; Walter M Stadler; Thomas Hutson; Martin E Gore; Alain Ravaud; Sergio Bracarda; Cristina Suárez; Riccardo Danielli; Viktor Gruenwald; Toni K Choueiri; Dorothee Nickles; Suchit Jhunjhunwala; Elisabeth Piault-Louis; Alpa Thobhani; Jiaheng Qiu; Daniel S Chen; Priti S Hegde; Christina Schiff; Gregg D Fine; Thomas Powles Journal: Nat Med Date: 2018-06-04 Impact factor: 53.440