Treatment beyond progression in patients with advanced renal cell carcinoma treated with nivolumab in CheckMate 025

Bernard Escudier, Robert J. Motzer, Padmanee Sharma, John Wagstaff, Elizabeth R. Plimack, Hans J. Hammers, Frede Donskov, Howard Gurney, Jeffrey A. Sosman, Pawel G. Zalewski, Ulrika Harmenberg, David F. McDermott, Toni K. Choueiri, Martin Richardet, Yoshihiko Tomita, Alain Ravaud, Justin Doan, Huanyu Zhao, Helene Hardy, Saby George

Research output: Contribution to journalArticleResearchpeer-review

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 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. Some patients with previously treated advanced renal cell carcinoma who were not clinically deteriorating and who were subsequently treated with nivolumab beyond progression had a reduction in tumor burden and improved overall survival versus patients who were not treated beyond progression, and an acceptable safety profile.

LanguageEnglish
Pages368-376
Number of pages9
JournalEuropean Urology
Volume72
Issue number3
DOIs
Publication statusPublished - Sep 2017

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Renal Cell Carcinoma
Therapeutics
Karnofsky Performance Status
Response Evaluation Criteria in Solid Tumors
nivolumab
Tumor Burden
Safety
Neoplasms
Incidence
Disease Progression

Keywords

  • Advanced renal cell carcinoma
  • Everolimus
  • Nivolumab
  • Phase 3
  • Treatment beyond progression

Cite this

Escudier, B., Motzer, R. J., Sharma, P., Wagstaff, J., Plimack, E. R., Hammers, H. J., ... George, S. (2017). Treatment beyond progression in patients with advanced renal cell carcinoma treated with nivolumab in CheckMate 025. European Urology, 72(3), 368-376. https://doi.org/10.1016/j.eururo.2017.03.037
Escudier, Bernard ; Motzer, Robert J. ; Sharma, Padmanee ; Wagstaff, John ; Plimack, Elizabeth R. ; Hammers, Hans J. ; Donskov, Frede ; Gurney, Howard ; Sosman, Jeffrey A. ; Zalewski, Pawel G. ; Harmenberg, Ulrika ; McDermott, David F. ; Choueiri, Toni K. ; Richardet, Martin ; Tomita, Yoshihiko ; Ravaud, Alain ; Doan, Justin ; Zhao, Huanyu ; Hardy, Helene ; George, Saby. / Treatment beyond progression in patients with advanced renal cell carcinoma treated with nivolumab in CheckMate 025. In: European Urology. 2017 ; Vol. 72, No. 3. pp. 368-376.
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title = "Treatment beyond progression in patients with advanced renal cell carcinoma treated with nivolumab in CheckMate 025",
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 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. Some patients with previously treated advanced renal cell carcinoma who were not clinically deteriorating and who were subsequently treated with nivolumab beyond progression had a reduction in tumor burden and improved overall survival versus patients who were not treated beyond progression, and an acceptable safety profile.",
keywords = "Advanced renal cell carcinoma, Everolimus, Nivolumab, Phase 3, Treatment beyond progression",
author = "Bernard Escudier and Motzer, {Robert J.} and Padmanee Sharma and John Wagstaff and Plimack, {Elizabeth R.} and Hammers, {Hans J.} and Frede Donskov and Howard Gurney and Sosman, {Jeffrey A.} and Zalewski, {Pawel G.} and Ulrika Harmenberg and McDermott, {David F.} and Choueiri, {Toni K.} and Martin Richardet and Yoshihiko Tomita and Alain Ravaud and Justin Doan and Huanyu Zhao and Helene Hardy and Saby George",
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Escudier, B, Motzer, RJ, Sharma, P, Wagstaff, J, Plimack, ER, Hammers, HJ, Donskov, F, Gurney, H, Sosman, JA, Zalewski, PG, Harmenberg, U, McDermott, DF, Choueiri, TK, Richardet, M, Tomita, Y, Ravaud, A, Doan, J, Zhao, H, Hardy, H & George, S 2017, 'Treatment beyond progression in patients with advanced renal cell carcinoma treated with nivolumab in CheckMate 025', European Urology, vol. 72, no. 3, pp. 368-376. https://doi.org/10.1016/j.eururo.2017.03.037

Treatment beyond progression in patients with advanced renal cell carcinoma treated with nivolumab in CheckMate 025. / Escudier, Bernard; Motzer, Robert J.; Sharma, Padmanee; Wagstaff, John; Plimack, Elizabeth R.; Hammers, Hans J.; Donskov, Frede; Gurney, Howard; Sosman, Jeffrey A.; Zalewski, Pawel G.; Harmenberg, Ulrika; McDermott, David F.; Choueiri, Toni K.; Richardet, Martin; Tomita, Yoshihiko; Ravaud, Alain; Doan, Justin; Zhao, Huanyu; Hardy, Helene; George, Saby.

In: European Urology, Vol. 72, No. 3, 09.2017, p. 368-376.

Research output: Contribution to journalArticleResearchpeer-review

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

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. Some patients with previously treated advanced renal cell carcinoma who were not clinically deteriorating and who were subsequently treated with nivolumab beyond progression had a reduction in tumor burden and improved overall survival versus patients who were not treated beyond progression, 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. Some patients with previously treated advanced renal cell carcinoma who were not clinically deteriorating and who were subsequently treated with nivolumab beyond progression had a reduction in tumor burden and improved overall survival versus patients who were not treated beyond progression, and an acceptable safety profile.

KW - Advanced renal cell carcinoma

KW - Everolimus

KW - Nivolumab

KW - Phase 3

KW - Treatment beyond progression

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U2 - 10.1016/j.eururo.2017.03.037

DO - 10.1016/j.eururo.2017.03.037

M3 - Article

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SP - 368

EP - 376

JO - European Urology

T2 - European Urology

JF - European Urology

SN - 0302-2838

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