TY - JOUR
T1 - Treatment Beyond Progression in Patients with Advanced Renal Cell Carcinoma Treated with Nivolumab in CheckMate 025
AU - Escudier, Bernard
AU - Motzer, Robert J.
AU - Sharma, Padmanee
AU - Wagstaff, John
AU - Plimack, Elizabeth R.
AU - Hammers, Hans J.
AU - Donskov, Frede
AU - Gurney, Howard
AU - Sosman, Jeffrey A.
AU - Zalewski, Pawel G.
AU - Harmenberg, Ulrika
AU - McDermott, David F.
AU - Choueiri, Toni K.
AU - Richardet, Martin
AU - Tomita, Yoshihiko
AU - Ravaud, Alain
AU - Doan, Justin
AU - Zhao, Huanyu
AU - Hardy, Helene
AU - George, Saby
N1 - Publisher Copyright:
© 2017 European Association of Urology
PY - 2017/9
Y1 - 2017/9
N2 - 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 3 mg/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 patients TBP and NTBP, respectively. Differences in clinical characteristics assessed at first progression between patients TBP 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 patients TBP (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 patients TBP 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.
AB - 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 3 mg/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 patients TBP and NTBP, respectively. Differences in clinical characteristics assessed at first progression between patients TBP 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 patients TBP (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 patients TBP 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.
KW - Advanced renal cell carcinoma
KW - Everolimus
KW - Nivolumab
KW - Phase 3
KW - Treatment beyond progression
UR - http://www.scopus.com/inward/record.url?scp=85017479187&partnerID=8YFLogxK
UR - https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=purepublist2023&SrcAuth=WosAPI&KeyUT=WOS:000407960100022&DestLinkType=FullRecord&DestApp=WOS
U2 - 10.1016/j.eururo.2017.03.037
DO - 10.1016/j.eururo.2017.03.037
M3 - Article
C2 - 28410865
SN - 0302-2838
VL - 72
SP - 368
EP - 376
JO - European Urology
JF - European Urology
IS - 3
ER -