Bernard Escudier1, Robert J Motzer2, Padmanee Sharma3, John Wagstaff4, Elizabeth R Plimack5, Hans J Hammers6, Frede Donskov7, Howard Gurney8, Jeffrey A Sosman9, Pawel G Zalewski10, Ulrika Harmenberg11, David F McDermott12, Toni K Choueiri13, Martin Richardet14, Yoshihiko Tomita15, Alain Ravaud16, Justin Doan17, Huanyu Zhao17, Helene Hardy17, Saby George18. 1. Department of Medical Oncology, Gustave Roussy, Villejuif, France. Electronic address: escudier@gustaveroussy.fr. 2. Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA. 3. Department of Genitourinary Medical Oncology, Department of Immunology, MD Anderson Cancer Center, University of Texas, Houston, TX, USA. 4. Department of Medical Oncology, South West Wales Cancer Institute and Swansea University College of Medicine, Swansea, UK. 5. Department of Hematology/Oncology, Fox Chase Cancer Center, Philadelphia, PA, USA. 6. Department of Medical Oncology, Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD, USA. 7. Department of Oncology, Aarhus University Hospital, Aarhus, Denmark. 8. Department of Medical Oncology, Westmead Hospital and Macquarie University, Sydney, Australia. 9. Department of Hematology, Vanderbilt University Medical Center, Nashville, TN, USA. 10. Department of Oncology, Lakeridge Health RS McLaughlin Durham Regional Cancer Centre, Oshawa, ON, Canada. 11. Department of Oncology, Radiumhemmet, Karolinska University Hospital, Stockholm, Sweden. 12. Biologic Therapy and Cutaneous Oncology Programs, Beth Israel Deaconess Medical Center, Dana-Farber/Harvard Cancer Center, Boston, MA, USA. 13. Kidney Cancer Center, Department of Medical Oncology, Dana-Farber Cancer Institute/Brigham and Women's Hospital, Boston, MA, USA. 14. Department of Medical Oncology, Instituto Oncologico de Cordoba, Cordoba, Argentina. 15. Department of Urology, Department of Molecular Oncology, Niigata University, Niigata, Japan. 16. Department of Medical Oncology and Radiotherapy, Bordeaux University Hospital, Hôpital Saint André, Bordeaux, France. 17. Bristol-Myers Squibb, Princeton, NJ, USA. 18. Department of Medicine, Roswell Park Cancer Institute, Buffalo, NY, USA.
Abstract
BACKGROUND: Response patterns to nivolumab differ from those seen with other approved targeted therapies. OBJECTIVE: To investigate the efficacy of nivolumab in previously treated patients with advanced renal cell carcinoma who were treated beyond (Response Evaluation Criteria In Solid Tumors) RECIST progression. DESIGN, SETTING, AND PARTICIPANTS: This was a subgroup analysis of patients treated with nivolumab in the phase 3 CheckMate 025 study. Patients continuing to tolerate therapy and exhibiting investigator-assessed clinical benefit were eligible to be treated beyond RECIST progression (TBP) and received therapy for ≥4 wk after first progression; patients not treated beyond RECIST progression (NTBP) received 0 wk to <4 wk of therapy after progression. INTERVENTIONS:Nivolumab 3mg/kg intravenously every 2 wk. RESULTS AND LIMITATIONS: Of 406 nivolumab-treated patients, 316 (78%) progressed by RECIST criteria. Of those who progressed, 48% were TBP, 52% were NTBP. Before being TBP, objective response rate (95% confidence interval) was 20% (14-28) and 14% (9-21) in patientsTBP and NTBP, respectively. Differences in clinical characteristics assessed at first progression between patientsTBP versus NTBP included better Karnofsky performance status, less deterioration in Karnofsky performance status, shorter time to response, lower incidence of new bone lesions, and improved quality of life. Postprogression, 13% of all patientsTBP (20/153) had ≥30% tumor burden reduction including patients with preprogression and postprogression tumor measurements (n=142) and complete/partial response (28%, 8/29), stable disease (6%, 3/47), and progressive disease (14%, 9/66) as their best response before being TBP. Incidence of treatment-related adverse events in patientsTBP was lower after (59%) versus before (71%) progression. Limitations included potential bias from the nonrandomized nature of the analysis. CONCLUSIONS: A subset of patients with advanced renal cell carcinoma and RECIST progression experienced tumor reduction postprogression with nivolumab, and had an acceptable safety profile. Clinical judgment remains essential when switching therapy. ClinicalTrials.gov Identifier: NCT01668784. PATIENT SUMMARY: A subset of patients with advanced renal cell carcinoma and disease progression may continue to benefit from nivolumab treatment beyond progression as evidenced by tumor reduction postprogression and an acceptable safety profile.
RCT Entities:
BACKGROUND: Response patterns to nivolumab differ from those seen with other approved targeted therapies. OBJECTIVE: To investigate the efficacy of nivolumab in previously treated patients with advanced renal cell carcinoma who were treated beyond (Response Evaluation Criteria In Solid Tumors) RECIST progression. DESIGN, SETTING, AND PARTICIPANTS: This was a subgroup analysis of patients treated with nivolumab in the phase 3 CheckMate 025 study. Patients continuing to tolerate therapy and exhibiting investigator-assessed clinical benefit were eligible to be treated beyond RECIST progression (TBP) and received therapy for ≥4 wk after first progression; patients not treated beyond RECIST progression (NTBP) received 0 wk to <4 wk of therapy after progression. INTERVENTIONS:Nivolumab 3mg/kg intravenously every 2 wk. RESULTS AND LIMITATIONS: Of 406 nivolumab-treated patients, 316 (78%) progressed by RECIST criteria. Of those who progressed, 48% were TBP, 52% were NTBP. Before being TBP, objective response rate (95% confidence interval) was 20% (14-28) and 14% (9-21) in patientsTBP and NTBP, respectively. Differences in clinical characteristics assessed at first progression between patientsTBP versus NTBP included better Karnofsky performance status, less deterioration in Karnofsky performance status, shorter time to response, lower incidence of new bone lesions, and improved quality of life. Postprogression, 13% of all patientsTBP (20/153) had ≥30% tumor burden reduction including patients with preprogression and postprogression tumor measurements (n=142) and complete/partial response (28%, 8/29), stable disease (6%, 3/47), and progressive disease (14%, 9/66) as their best response before being TBP. Incidence of treatment-related adverse events in patientsTBP was lower after (59%) versus before (71%) progression. Limitations included potential bias from the nonrandomized nature of the analysis. CONCLUSIONS: A subset of patients with advanced renal cell carcinoma and RECIST progression experienced tumor reduction postprogression with nivolumab, and had an acceptable safety profile. Clinical judgment remains essential when switching therapy. ClinicalTrials.gov Identifier: NCT01668784. PATIENT SUMMARY: A subset of patients with advanced renal cell carcinoma and disease progression may continue to benefit from nivolumab treatment beyond progression as evidenced by tumor reduction postprogression and an acceptable safety profile.
Authors: Daniel Reinhorn; Michal Sarfaty; Moshe Leshno; Assaf Moore; Victoria Neiman; Eli Rosenbaum; Daniel A Goldstein Journal: Oncologist Date: 2019-02-01