Evaluation of immune-related response criteria and RECIST v1.1 in patients with advanced melanoma treated with Pembrolizumab

F. Stephen Hodi, Wen Jen Hwu, Richard Kefford, Jeffrey S. Weber, Adil Daud, Omid Hamid, Amita Patnaik, Antoni Ribas, Caroline Robert, Tara C. Gangadhar, Anthony M. Joshua, Peter Hersey, Roxana S Dronca, Richard W Joseph, Darcy Hille, Dahai Xue, Xiaoyun Nicole Li, S. Peter Kang, Scot Ebbinghaus, Andrea PerroneJedd D. Wolchok

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Abstract

Purpose We evaluated atypical response patterns and the relationship between overall survival and best overall response measured per immune-related response criteria (irRC) and Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST v1.1) in patients with advanced melanoma treated with pembrolizumab in the phase Ib KEYNOTE-001 study (clinical trial information: NCT01295827). Patients and Methods Patients received pembrolizumab 2 or 10 mg/kg every 2 weeks or every 3 weeks. Atypical responses were identified by using centrally assessed irRC data in patients with ≥ 28 weeks of imaging. Pseudoprogression was defined as ≥ 25% increase in tumor burden at week 12 (early) or any assessment after week 12 (delayed) that was not confirmed as progressive disease at next assessment. Response was assessed centrally per irRC and RECIST v1.1. Results Of the 655 patients with melanoma enrolled, 327 had ≥ 28 weeks of imaging follow-up. Twenty-four (7%) of these 327 patients had atypical responses (15 [5%] with early pseudoprogression and nine [3%] with delayed pseudoprogression). Of the 592 patients who survived ≥ 12 weeks, 84 (14%) experienced progressive disease per RECIST v1.1 but nonprogressive disease per irRC. Two-year overall survival rates were 77.6% in patients with nonprogressive disease per both criteria (n = 331), 37.5% in patients with progressive disease per RECIST v1.1 but nonprogressive disease per irRC (n = 84), and 17.3% in patients with progressive disease per both criteria (n = 177). Conclusion Atypical responses were observed in patients with melanoma treated with pembrolizumab. Based on survival analysis, conventional RECIST might underestimate the benefit of pembrolizumab in approximately 15% of patients; modified criteria that permit treatment beyond initial progression per RECIST v1.1 might prevent premature cessation of treatment.

Original languageEnglish (US)
Pages (from-to)1510-1517
Number of pages8
JournalJournal of Clinical Oncology
Volume34
Issue number13
DOIs
StatePublished - May 1 2016

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Melanoma
Immune System Diseases
Response Evaluation Criteria in Solid Tumors
pembrolizumab
Withholding Treatment
Survival Analysis
Tumor Burden
Survival Rate
Clinical Trials
Survival

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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Evaluation of immune-related response criteria and RECIST v1.1 in patients with advanced melanoma treated with Pembrolizumab. / Hodi, F. Stephen; Hwu, Wen Jen; Kefford, Richard; Weber, Jeffrey S.; Daud, Adil; Hamid, Omid; Patnaik, Amita; Ribas, Antoni; Robert, Caroline; Gangadhar, Tara C.; Joshua, Anthony M.; Hersey, Peter; Dronca, Roxana S; Joseph, Richard W; Hille, Darcy; Xue, Dahai; Li, Xiaoyun Nicole; Kang, S. Peter; Ebbinghaus, Scot; Perrone, Andrea; Wolchok, Jedd D.

In: Journal of Clinical Oncology, Vol. 34, No. 13, 01.05.2016, p. 1510-1517.

Research output: Contribution to journalArticle

Hodi, FS, Hwu, WJ, Kefford, R, Weber, JS, Daud, A, Hamid, O, Patnaik, A, Ribas, A, Robert, C, Gangadhar, TC, Joshua, AM, Hersey, P, Dronca, RS, Joseph, RW, Hille, D, Xue, D, Li, XN, Kang, SP, Ebbinghaus, S, Perrone, A & Wolchok, JD 2016, 'Evaluation of immune-related response criteria and RECIST v1.1 in patients with advanced melanoma treated with Pembrolizumab', Journal of Clinical Oncology, vol. 34, no. 13, pp. 1510-1517. https://doi.org/10.1200/JCO.2015.64.0391
Hodi, F. Stephen ; Hwu, Wen Jen ; Kefford, Richard ; Weber, Jeffrey S. ; Daud, Adil ; Hamid, Omid ; Patnaik, Amita ; Ribas, Antoni ; Robert, Caroline ; Gangadhar, Tara C. ; Joshua, Anthony M. ; Hersey, Peter ; Dronca, Roxana S ; Joseph, Richard W ; Hille, Darcy ; Xue, Dahai ; Li, Xiaoyun Nicole ; Kang, S. Peter ; Ebbinghaus, Scot ; Perrone, Andrea ; Wolchok, Jedd D. / Evaluation of immune-related response criteria and RECIST v1.1 in patients with advanced melanoma treated with Pembrolizumab. In: Journal of Clinical Oncology. 2016 ; Vol. 34, No. 13. pp. 1510-1517.
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title = "Evaluation of immune-related response criteria and RECIST v1.1 in patients with advanced melanoma treated with Pembrolizumab",
abstract = "Purpose We evaluated atypical response patterns and the relationship between overall survival and best overall response measured per immune-related response criteria (irRC) and Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST v1.1) in patients with advanced melanoma treated with pembrolizumab in the phase Ib KEYNOTE-001 study (clinical trial information: NCT01295827). Patients and Methods Patients received pembrolizumab 2 or 10 mg/kg every 2 weeks or every 3 weeks. Atypical responses were identified by using centrally assessed irRC data in patients with ≥ 28 weeks of imaging. Pseudoprogression was defined as ≥ 25{\%} increase in tumor burden at week 12 (early) or any assessment after week 12 (delayed) that was not confirmed as progressive disease at next assessment. Response was assessed centrally per irRC and RECIST v1.1. Results Of the 655 patients with melanoma enrolled, 327 had ≥ 28 weeks of imaging follow-up. Twenty-four (7{\%}) of these 327 patients had atypical responses (15 [5{\%}] with early pseudoprogression and nine [3{\%}] with delayed pseudoprogression). Of the 592 patients who survived ≥ 12 weeks, 84 (14{\%}) experienced progressive disease per RECIST v1.1 but nonprogressive disease per irRC. Two-year overall survival rates were 77.6{\%} in patients with nonprogressive disease per both criteria (n = 331), 37.5{\%} in patients with progressive disease per RECIST v1.1 but nonprogressive disease per irRC (n = 84), and 17.3{\%} in patients with progressive disease per both criteria (n = 177). Conclusion Atypical responses were observed in patients with melanoma treated with pembrolizumab. Based on survival analysis, conventional RECIST might underestimate the benefit of pembrolizumab in approximately 15{\%} of patients; modified criteria that permit treatment beyond initial progression per RECIST v1.1 might prevent premature cessation of treatment.",
author = "Hodi, {F. Stephen} and Hwu, {Wen Jen} and Richard Kefford and Weber, {Jeffrey S.} and Adil Daud and Omid Hamid and Amita Patnaik and Antoni Ribas and Caroline Robert and Gangadhar, {Tara C.} and Joshua, {Anthony M.} and Peter Hersey and Dronca, {Roxana S} and Joseph, {Richard W} and Darcy Hille and Dahai Xue and Li, {Xiaoyun Nicole} and Kang, {S. Peter} and Scot Ebbinghaus and Andrea Perrone and Wolchok, {Jedd D.}",
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T1 - Evaluation of immune-related response criteria and RECIST v1.1 in patients with advanced melanoma treated with Pembrolizumab

AU - Hodi, F. Stephen

AU - Hwu, Wen Jen

AU - Kefford, Richard

AU - Weber, Jeffrey S.

AU - Daud, Adil

AU - Hamid, Omid

AU - Patnaik, Amita

AU - Ribas, Antoni

AU - Robert, Caroline

AU - Gangadhar, Tara C.

AU - Joshua, Anthony M.

AU - Hersey, Peter

AU - Dronca, Roxana S

AU - Joseph, Richard W

AU - Hille, Darcy

AU - Xue, Dahai

AU - Li, Xiaoyun Nicole

AU - Kang, S. Peter

AU - Ebbinghaus, Scot

AU - Perrone, Andrea

AU - Wolchok, Jedd D.

PY - 2016/5/1

Y1 - 2016/5/1

N2 - Purpose We evaluated atypical response patterns and the relationship between overall survival and best overall response measured per immune-related response criteria (irRC) and Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST v1.1) in patients with advanced melanoma treated with pembrolizumab in the phase Ib KEYNOTE-001 study (clinical trial information: NCT01295827). Patients and Methods Patients received pembrolizumab 2 or 10 mg/kg every 2 weeks or every 3 weeks. Atypical responses were identified by using centrally assessed irRC data in patients with ≥ 28 weeks of imaging. Pseudoprogression was defined as ≥ 25% increase in tumor burden at week 12 (early) or any assessment after week 12 (delayed) that was not confirmed as progressive disease at next assessment. Response was assessed centrally per irRC and RECIST v1.1. Results Of the 655 patients with melanoma enrolled, 327 had ≥ 28 weeks of imaging follow-up. Twenty-four (7%) of these 327 patients had atypical responses (15 [5%] with early pseudoprogression and nine [3%] with delayed pseudoprogression). Of the 592 patients who survived ≥ 12 weeks, 84 (14%) experienced progressive disease per RECIST v1.1 but nonprogressive disease per irRC. Two-year overall survival rates were 77.6% in patients with nonprogressive disease per both criteria (n = 331), 37.5% in patients with progressive disease per RECIST v1.1 but nonprogressive disease per irRC (n = 84), and 17.3% in patients with progressive disease per both criteria (n = 177). Conclusion Atypical responses were observed in patients with melanoma treated with pembrolizumab. Based on survival analysis, conventional RECIST might underestimate the benefit of pembrolizumab in approximately 15% of patients; modified criteria that permit treatment beyond initial progression per RECIST v1.1 might prevent premature cessation of treatment.

AB - Purpose We evaluated atypical response patterns and the relationship between overall survival and best overall response measured per immune-related response criteria (irRC) and Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST v1.1) in patients with advanced melanoma treated with pembrolizumab in the phase Ib KEYNOTE-001 study (clinical trial information: NCT01295827). Patients and Methods Patients received pembrolizumab 2 or 10 mg/kg every 2 weeks or every 3 weeks. Atypical responses were identified by using centrally assessed irRC data in patients with ≥ 28 weeks of imaging. Pseudoprogression was defined as ≥ 25% increase in tumor burden at week 12 (early) or any assessment after week 12 (delayed) that was not confirmed as progressive disease at next assessment. Response was assessed centrally per irRC and RECIST v1.1. Results Of the 655 patients with melanoma enrolled, 327 had ≥ 28 weeks of imaging follow-up. Twenty-four (7%) of these 327 patients had atypical responses (15 [5%] with early pseudoprogression and nine [3%] with delayed pseudoprogression). Of the 592 patients who survived ≥ 12 weeks, 84 (14%) experienced progressive disease per RECIST v1.1 but nonprogressive disease per irRC. Two-year overall survival rates were 77.6% in patients with nonprogressive disease per both criteria (n = 331), 37.5% in patients with progressive disease per RECIST v1.1 but nonprogressive disease per irRC (n = 84), and 17.3% in patients with progressive disease per both criteria (n = 177). Conclusion Atypical responses were observed in patients with melanoma treated with pembrolizumab. Based on survival analysis, conventional RECIST might underestimate the benefit of pembrolizumab in approximately 15% of patients; modified criteria that permit treatment beyond initial progression per RECIST v1.1 might prevent premature cessation of treatment.

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