Final overall survival analysis for the phase II RECORD-3 study of first-line everolimus followed by sunitinib versus first-line sunitinib followed by everolimus in metastatic RCC

J. J. Knox, C. H. Barrios, T. M. Kim, T. Cosgriff, V. Srimuninnimit, K. Pittman, R. Sabbatini, SunYoung Rha, T. W. Flaig, R. D. Page, J. T. Beck, F. Cheung, S. Yadav, P. Patel, L. Geoffrois, J. Niolat, N. Berkowitz, M. Marker, D. Chen, R. J. Motzer

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Background: RECORD-3 compared everolimus and sunitinib as first-line therapy, and the sequence of everolimus followed bysunitinib at progression compared with the opposite (standard) sequence in patients with metastatic renal cell carcinoma(mRCC). This final overall survival (OS) analysis evaluated mature data for secondary end points. Patients and methods: Patients received either first-line everolimus followed by second-line sunitinib at progression (n=238)or first-line sunitinib followed by second-line everolimus (n=233). Secondary end points were combined first- and second-lineprogression-free survival (PFS), OS, and safety. The impacts of neutrophil lymphocyte ratio (NLR) and baseline levels of solublebiomarkers on OS were explored. Results: At final analysis, median duration of exposure was 5.6 months for everolimus and 8.3 months for sunitinib. Median combined PFS was 21.7 months [95% confidence interval (CI) 15.1-26.7] with everolimus-sunitinib and 22.2 months(95% CI 16.0-29.8) with sunitinib-everolimus [hazard ratio (HR)EVE-SUN/SUN-EVE, 1.2; 95% CI 0.9-1.6]. Median OS was 22.4 months(95% CI 18.6-33.3) for everolimus-sunitinib and 29.5 months (95% CI 22.8-33.1) for sunitinib-everolimus (HREVE-SUN/SUN-EVE, 1.1;95% CI 0.9-1.4). The rates of grade 3 and 4 adverse events suspected to be related to second-line therapy were 47% with everolimusand 57% with sunitinib. Higher NLR and 12 soluble biomarker levels were identified as prognostic markers for poor OS withthe association being largely independent of treatment sequences. Conclusions: Results of this final OS analysis support the sequence of sunitinib followed by everolimus at progression inpatients with mRCC. The safety profiles of everolimus and sunitinib were consistent with those previously reported, and therewere no unexpected safety signals.

Original languageEnglish
Article numbermdx075
Pages (from-to)1339-1345
Number of pages7
JournalAnnals of Oncology
Volume28
Issue number6
DOIs
Publication statusPublished - 2017 Jun 1

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Survival Analysis
Confidence Intervals
Survival
Safety
Renal Cell Carcinoma
Neutrophils
sunitinib
Everolimus
Lymphocytes
Inpatients
Therapeutics
Biomarkers

All Science Journal Classification (ASJC) codes

  • Hematology
  • Oncology

Cite this

Knox, J. J. ; Barrios, C. H. ; Kim, T. M. ; Cosgriff, T. ; Srimuninnimit, V. ; Pittman, K. ; Sabbatini, R. ; Rha, SunYoung ; Flaig, T. W. ; Page, R. D. ; Beck, J. T. ; Cheung, F. ; Yadav, S. ; Patel, P. ; Geoffrois, L. ; Niolat, J. ; Berkowitz, N. ; Marker, M. ; Chen, D. ; Motzer, R. J. / Final overall survival analysis for the phase II RECORD-3 study of first-line everolimus followed by sunitinib versus first-line sunitinib followed by everolimus in metastatic RCC. In: Annals of Oncology. 2017 ; Vol. 28, No. 6. pp. 1339-1345.
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title = "Final overall survival analysis for the phase II RECORD-3 study of first-line everolimus followed by sunitinib versus first-line sunitinib followed by everolimus in metastatic RCC",
abstract = "Background: RECORD-3 compared everolimus and sunitinib as first-line therapy, and the sequence of everolimus followed bysunitinib at progression compared with the opposite (standard) sequence in patients with metastatic renal cell carcinoma(mRCC). This final overall survival (OS) analysis evaluated mature data for secondary end points. Patients and methods: Patients received either first-line everolimus followed by second-line sunitinib at progression (n=238)or first-line sunitinib followed by second-line everolimus (n=233). Secondary end points were combined first- and second-lineprogression-free survival (PFS), OS, and safety. The impacts of neutrophil lymphocyte ratio (NLR) and baseline levels of solublebiomarkers on OS were explored. Results: At final analysis, median duration of exposure was 5.6 months for everolimus and 8.3 months for sunitinib. Median combined PFS was 21.7 months [95{\%} confidence interval (CI) 15.1-26.7] with everolimus-sunitinib and 22.2 months(95{\%} CI 16.0-29.8) with sunitinib-everolimus [hazard ratio (HR)EVE-SUN/SUN-EVE, 1.2; 95{\%} CI 0.9-1.6]. Median OS was 22.4 months(95{\%} CI 18.6-33.3) for everolimus-sunitinib and 29.5 months (95{\%} CI 22.8-33.1) for sunitinib-everolimus (HREVE-SUN/SUN-EVE, 1.1;95{\%} CI 0.9-1.4). The rates of grade 3 and 4 adverse events suspected to be related to second-line therapy were 47{\%} with everolimusand 57{\%} with sunitinib. Higher NLR and 12 soluble biomarker levels were identified as prognostic markers for poor OS withthe association being largely independent of treatment sequences. Conclusions: Results of this final OS analysis support the sequence of sunitinib followed by everolimus at progression inpatients with mRCC. The safety profiles of everolimus and sunitinib were consistent with those previously reported, and therewere no unexpected safety signals.",
author = "Knox, {J. J.} and Barrios, {C. H.} and Kim, {T. M.} and T. Cosgriff and V. Srimuninnimit and K. Pittman and R. Sabbatini and SunYoung Rha and Flaig, {T. W.} and Page, {R. D.} and Beck, {J. T.} and F. Cheung and S. Yadav and P. Patel and L. Geoffrois and J. Niolat and N. Berkowitz and M. Marker and D. Chen and Motzer, {R. J.}",
year = "2017",
month = "6",
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doi = "10.1093/annonc/mdx075",
language = "English",
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pages = "1339--1345",
journal = "Annals of Oncology",
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Knox, JJ, Barrios, CH, Kim, TM, Cosgriff, T, Srimuninnimit, V, Pittman, K, Sabbatini, R, Rha, S, Flaig, TW, Page, RD, Beck, JT, Cheung, F, Yadav, S, Patel, P, Geoffrois, L, Niolat, J, Berkowitz, N, Marker, M, Chen, D & Motzer, RJ 2017, 'Final overall survival analysis for the phase II RECORD-3 study of first-line everolimus followed by sunitinib versus first-line sunitinib followed by everolimus in metastatic RCC', Annals of Oncology, vol. 28, no. 6, mdx075, pp. 1339-1345. https://doi.org/10.1093/annonc/mdx075

Final overall survival analysis for the phase II RECORD-3 study of first-line everolimus followed by sunitinib versus first-line sunitinib followed by everolimus in metastatic RCC. / Knox, J. J.; Barrios, C. H.; Kim, T. M.; Cosgriff, T.; Srimuninnimit, V.; Pittman, K.; Sabbatini, R.; Rha, SunYoung; Flaig, T. W.; Page, R. D.; Beck, J. T.; Cheung, F.; Yadav, S.; Patel, P.; Geoffrois, L.; Niolat, J.; Berkowitz, N.; Marker, M.; Chen, D.; Motzer, R. J.

In: Annals of Oncology, Vol. 28, No. 6, mdx075, 01.06.2017, p. 1339-1345.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Final overall survival analysis for the phase II RECORD-3 study of first-line everolimus followed by sunitinib versus first-line sunitinib followed by everolimus in metastatic RCC

AU - Knox, J. J.

AU - Barrios, C. H.

AU - Kim, T. M.

AU - Cosgriff, T.

AU - Srimuninnimit, V.

AU - Pittman, K.

AU - Sabbatini, R.

AU - Rha, SunYoung

AU - Flaig, T. W.

AU - Page, R. D.

AU - Beck, J. T.

AU - Cheung, F.

AU - Yadav, S.

AU - Patel, P.

AU - Geoffrois, L.

AU - Niolat, J.

AU - Berkowitz, N.

AU - Marker, M.

AU - Chen, D.

AU - Motzer, R. J.

PY - 2017/6/1

Y1 - 2017/6/1

N2 - Background: RECORD-3 compared everolimus and sunitinib as first-line therapy, and the sequence of everolimus followed bysunitinib at progression compared with the opposite (standard) sequence in patients with metastatic renal cell carcinoma(mRCC). This final overall survival (OS) analysis evaluated mature data for secondary end points. Patients and methods: Patients received either first-line everolimus followed by second-line sunitinib at progression (n=238)or first-line sunitinib followed by second-line everolimus (n=233). Secondary end points were combined first- and second-lineprogression-free survival (PFS), OS, and safety. The impacts of neutrophil lymphocyte ratio (NLR) and baseline levels of solublebiomarkers on OS were explored. Results: At final analysis, median duration of exposure was 5.6 months for everolimus and 8.3 months for sunitinib. Median combined PFS was 21.7 months [95% confidence interval (CI) 15.1-26.7] with everolimus-sunitinib and 22.2 months(95% CI 16.0-29.8) with sunitinib-everolimus [hazard ratio (HR)EVE-SUN/SUN-EVE, 1.2; 95% CI 0.9-1.6]. Median OS was 22.4 months(95% CI 18.6-33.3) for everolimus-sunitinib and 29.5 months (95% CI 22.8-33.1) for sunitinib-everolimus (HREVE-SUN/SUN-EVE, 1.1;95% CI 0.9-1.4). The rates of grade 3 and 4 adverse events suspected to be related to second-line therapy were 47% with everolimusand 57% with sunitinib. Higher NLR and 12 soluble biomarker levels were identified as prognostic markers for poor OS withthe association being largely independent of treatment sequences. Conclusions: Results of this final OS analysis support the sequence of sunitinib followed by everolimus at progression inpatients with mRCC. The safety profiles of everolimus and sunitinib were consistent with those previously reported, and therewere no unexpected safety signals.

AB - Background: RECORD-3 compared everolimus and sunitinib as first-line therapy, and the sequence of everolimus followed bysunitinib at progression compared with the opposite (standard) sequence in patients with metastatic renal cell carcinoma(mRCC). This final overall survival (OS) analysis evaluated mature data for secondary end points. Patients and methods: Patients received either first-line everolimus followed by second-line sunitinib at progression (n=238)or first-line sunitinib followed by second-line everolimus (n=233). Secondary end points were combined first- and second-lineprogression-free survival (PFS), OS, and safety. The impacts of neutrophil lymphocyte ratio (NLR) and baseline levels of solublebiomarkers on OS were explored. Results: At final analysis, median duration of exposure was 5.6 months for everolimus and 8.3 months for sunitinib. Median combined PFS was 21.7 months [95% confidence interval (CI) 15.1-26.7] with everolimus-sunitinib and 22.2 months(95% CI 16.0-29.8) with sunitinib-everolimus [hazard ratio (HR)EVE-SUN/SUN-EVE, 1.2; 95% CI 0.9-1.6]. Median OS was 22.4 months(95% CI 18.6-33.3) for everolimus-sunitinib and 29.5 months (95% CI 22.8-33.1) for sunitinib-everolimus (HREVE-SUN/SUN-EVE, 1.1;95% CI 0.9-1.4). The rates of grade 3 and 4 adverse events suspected to be related to second-line therapy were 47% with everolimusand 57% with sunitinib. Higher NLR and 12 soluble biomarker levels were identified as prognostic markers for poor OS withthe association being largely independent of treatment sequences. Conclusions: Results of this final OS analysis support the sequence of sunitinib followed by everolimus at progression inpatients with mRCC. The safety profiles of everolimus and sunitinib were consistent with those previously reported, and therewere no unexpected safety signals.

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