Baseline tumor size is an independent prognostic factor for overall survival in patients with melanoma treated with pembrolizumab

Richard W Joseph, Jeroen Elassaiss-Schaap, Richard Kefford, Wen Jen Hwu, Jedd D. Wolchok, Anthony M. Joshua, Antoni Ribas, F. Stephen Hodi, Omid Hamid, Caroline Robert, Adil Daud, Roxana S Dronca, Peter Hersey, Jeffrey S. Weber, Amita Patnaik, Dinesh P. De Alwis, Andrea Perrone, Jin Zhang, S. Peter Kang, Scot EbbinghausKeaven M. Anderson, Tara C. Gangadhar

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

Purpose: The purpose of this study was to assess the association of baseline tumor size (BTS) with other baseline clinical factors and outcomes in pembrolizumab-treated patients with advanced melanoma in KEYNOTE-001 (NCT01295827). Experimental Design: BTS was quantified by adding the sum of the longest dimensions of all measurable baseline target lesions. BTS as a dichotomous and continuous variable was evaluated with other baseline factors using logistic regression for objective response rate (ORR) and Cox regression for overall survival (OS). Nominal P values with no multiplicity adjustment describe the strength of observed associations. Results: Per central review by RECIST v1.1, 583 of 655 patients had baseline measurable disease and were included in this post hoc analysis. Median BTS was 10.2 cm (range, 1-89.5). Larger median BTS was associated with Eastern Cooperative Oncology Group performance status 1, elevated lactate dehydrogenase (LDH), stage M1c disease, and liver metastases (with or without any other sites; all P ≤ 0.001). In univariate analyses, BTS below the median was associated with higher ORR (44% vs. 23%; P < 0.001) and improved OS (HR, 0.38; P < 0.001). In multivariate analyses, BTS below the median remained an independent prognostic marker of OS (P < 0.001) but not ORR. In 459 patients with available tumor programmed death ligand 1 (PD-L1) expression, BTS below the median and PD-L1-positive tumors were independently associated with higher ORR and longer OS. Conclusions: BTS is associated with many other baseline clinical factors but is also independently prognostic of survival in pembrolizumab-treated patients with advanced melanoma.

Original languageEnglish (US)
Pages (from-to)4960-4967
Number of pages8
JournalClinical Cancer Research
Volume24
Issue number20
DOIs
StatePublished - Oct 15 2018

Fingerprint

Melanoma
Survival
Neoplasms
pembrolizumab
Ligands
Liver Diseases
Research Design
Multivariate Analysis
Logistic Models
Neoplasm Metastasis

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Baseline tumor size is an independent prognostic factor for overall survival in patients with melanoma treated with pembrolizumab. / Joseph, Richard W; Elassaiss-Schaap, Jeroen; Kefford, Richard; Hwu, Wen Jen; Wolchok, Jedd D.; Joshua, Anthony M.; Ribas, Antoni; Hodi, F. Stephen; Hamid, Omid; Robert, Caroline; Daud, Adil; Dronca, Roxana S; Hersey, Peter; Weber, Jeffrey S.; Patnaik, Amita; De Alwis, Dinesh P.; Perrone, Andrea; Zhang, Jin; Kang, S. Peter; Ebbinghaus, Scot; Anderson, Keaven M.; Gangadhar, Tara C.

In: Clinical Cancer Research, Vol. 24, No. 20, 15.10.2018, p. 4960-4967.

Research output: Contribution to journalArticle

Joseph, RW, Elassaiss-Schaap, J, Kefford, R, Hwu, WJ, Wolchok, JD, Joshua, AM, Ribas, A, Hodi, FS, Hamid, O, Robert, C, Daud, A, Dronca, RS, Hersey, P, Weber, JS, Patnaik, A, De Alwis, DP, Perrone, A, Zhang, J, Kang, SP, Ebbinghaus, S, Anderson, KM & Gangadhar, TC 2018, 'Baseline tumor size is an independent prognostic factor for overall survival in patients with melanoma treated with pembrolizumab', Clinical Cancer Research, vol. 24, no. 20, pp. 4960-4967. https://doi.org/10.1158/1078-0432.CCR-17-2386
Joseph, Richard W ; Elassaiss-Schaap, Jeroen ; Kefford, Richard ; Hwu, Wen Jen ; Wolchok, Jedd D. ; Joshua, Anthony M. ; Ribas, Antoni ; Hodi, F. Stephen ; Hamid, Omid ; Robert, Caroline ; Daud, Adil ; Dronca, Roxana S ; Hersey, Peter ; Weber, Jeffrey S. ; Patnaik, Amita ; De Alwis, Dinesh P. ; Perrone, Andrea ; Zhang, Jin ; Kang, S. Peter ; Ebbinghaus, Scot ; Anderson, Keaven M. ; Gangadhar, Tara C. / Baseline tumor size is an independent prognostic factor for overall survival in patients with melanoma treated with pembrolizumab. In: Clinical Cancer Research. 2018 ; Vol. 24, No. 20. pp. 4960-4967.
@article{0ae99005eeb644f990ee6182f824f7dd,
title = "Baseline tumor size is an independent prognostic factor for overall survival in patients with melanoma treated with pembrolizumab",
abstract = "Purpose: The purpose of this study was to assess the association of baseline tumor size (BTS) with other baseline clinical factors and outcomes in pembrolizumab-treated patients with advanced melanoma in KEYNOTE-001 (NCT01295827). Experimental Design: BTS was quantified by adding the sum of the longest dimensions of all measurable baseline target lesions. BTS as a dichotomous and continuous variable was evaluated with other baseline factors using logistic regression for objective response rate (ORR) and Cox regression for overall survival (OS). Nominal P values with no multiplicity adjustment describe the strength of observed associations. Results: Per central review by RECIST v1.1, 583 of 655 patients had baseline measurable disease and were included in this post hoc analysis. Median BTS was 10.2 cm (range, 1-89.5). Larger median BTS was associated with Eastern Cooperative Oncology Group performance status 1, elevated lactate dehydrogenase (LDH), stage M1c disease, and liver metastases (with or without any other sites; all P ≤ 0.001). In univariate analyses, BTS below the median was associated with higher ORR (44{\%} vs. 23{\%}; P < 0.001) and improved OS (HR, 0.38; P < 0.001). In multivariate analyses, BTS below the median remained an independent prognostic marker of OS (P < 0.001) but not ORR. In 459 patients with available tumor programmed death ligand 1 (PD-L1) expression, BTS below the median and PD-L1-positive tumors were independently associated with higher ORR and longer OS. Conclusions: BTS is associated with many other baseline clinical factors but is also independently prognostic of survival in pembrolizumab-treated patients with advanced melanoma.",
author = "Joseph, {Richard W} and Jeroen Elassaiss-Schaap and Richard Kefford and Hwu, {Wen Jen} and Wolchok, {Jedd D.} and Joshua, {Anthony M.} and Antoni Ribas and Hodi, {F. Stephen} and Omid Hamid and Caroline Robert and Adil Daud and Dronca, {Roxana S} and Peter Hersey and Weber, {Jeffrey S.} and Amita Patnaik and {De Alwis}, {Dinesh P.} and Andrea Perrone and Jin Zhang and Kang, {S. Peter} and Scot Ebbinghaus and Anderson, {Keaven M.} and Gangadhar, {Tara C.}",
year = "2018",
month = "10",
day = "15",
doi = "10.1158/1078-0432.CCR-17-2386",
language = "English (US)",
volume = "24",
pages = "4960--4967",
journal = "Clinical Cancer Research",
issn = "1078-0432",
publisher = "American Association for Cancer Research Inc.",
number = "20",

}

TY - JOUR

T1 - Baseline tumor size is an independent prognostic factor for overall survival in patients with melanoma treated with pembrolizumab

AU - Joseph, Richard W

AU - Elassaiss-Schaap, Jeroen

AU - Kefford, Richard

AU - Hwu, Wen Jen

AU - Wolchok, Jedd D.

AU - Joshua, Anthony M.

AU - Ribas, Antoni

AU - Hodi, F. Stephen

AU - Hamid, Omid

AU - Robert, Caroline

AU - Daud, Adil

AU - Dronca, Roxana S

AU - Hersey, Peter

AU - Weber, Jeffrey S.

AU - Patnaik, Amita

AU - De Alwis, Dinesh P.

AU - Perrone, Andrea

AU - Zhang, Jin

AU - Kang, S. Peter

AU - Ebbinghaus, Scot

AU - Anderson, Keaven M.

AU - Gangadhar, Tara C.

PY - 2018/10/15

Y1 - 2018/10/15

N2 - Purpose: The purpose of this study was to assess the association of baseline tumor size (BTS) with other baseline clinical factors and outcomes in pembrolizumab-treated patients with advanced melanoma in KEYNOTE-001 (NCT01295827). Experimental Design: BTS was quantified by adding the sum of the longest dimensions of all measurable baseline target lesions. BTS as a dichotomous and continuous variable was evaluated with other baseline factors using logistic regression for objective response rate (ORR) and Cox regression for overall survival (OS). Nominal P values with no multiplicity adjustment describe the strength of observed associations. Results: Per central review by RECIST v1.1, 583 of 655 patients had baseline measurable disease and were included in this post hoc analysis. Median BTS was 10.2 cm (range, 1-89.5). Larger median BTS was associated with Eastern Cooperative Oncology Group performance status 1, elevated lactate dehydrogenase (LDH), stage M1c disease, and liver metastases (with or without any other sites; all P ≤ 0.001). In univariate analyses, BTS below the median was associated with higher ORR (44% vs. 23%; P < 0.001) and improved OS (HR, 0.38; P < 0.001). In multivariate analyses, BTS below the median remained an independent prognostic marker of OS (P < 0.001) but not ORR. In 459 patients with available tumor programmed death ligand 1 (PD-L1) expression, BTS below the median and PD-L1-positive tumors were independently associated with higher ORR and longer OS. Conclusions: BTS is associated with many other baseline clinical factors but is also independently prognostic of survival in pembrolizumab-treated patients with advanced melanoma.

AB - Purpose: The purpose of this study was to assess the association of baseline tumor size (BTS) with other baseline clinical factors and outcomes in pembrolizumab-treated patients with advanced melanoma in KEYNOTE-001 (NCT01295827). Experimental Design: BTS was quantified by adding the sum of the longest dimensions of all measurable baseline target lesions. BTS as a dichotomous and continuous variable was evaluated with other baseline factors using logistic regression for objective response rate (ORR) and Cox regression for overall survival (OS). Nominal P values with no multiplicity adjustment describe the strength of observed associations. Results: Per central review by RECIST v1.1, 583 of 655 patients had baseline measurable disease and were included in this post hoc analysis. Median BTS was 10.2 cm (range, 1-89.5). Larger median BTS was associated with Eastern Cooperative Oncology Group performance status 1, elevated lactate dehydrogenase (LDH), stage M1c disease, and liver metastases (with or without any other sites; all P ≤ 0.001). In univariate analyses, BTS below the median was associated with higher ORR (44% vs. 23%; P < 0.001) and improved OS (HR, 0.38; P < 0.001). In multivariate analyses, BTS below the median remained an independent prognostic marker of OS (P < 0.001) but not ORR. In 459 patients with available tumor programmed death ligand 1 (PD-L1) expression, BTS below the median and PD-L1-positive tumors were independently associated with higher ORR and longer OS. Conclusions: BTS is associated with many other baseline clinical factors but is also independently prognostic of survival in pembrolizumab-treated patients with advanced melanoma.

UR - http://www.scopus.com/inward/record.url?scp=85049240906&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85049240906&partnerID=8YFLogxK

U2 - 10.1158/1078-0432.CCR-17-2386

DO - 10.1158/1078-0432.CCR-17-2386

M3 - Article

C2 - 29685882

AN - SCOPUS:85049240906

VL - 24

SP - 4960

EP - 4967

JO - Clinical Cancer Research

JF - Clinical Cancer Research

SN - 1078-0432

IS - 20

ER -