TBCRC026

Phase II Trial Correlating Standardized Uptake Value With Pathologic Complete Response to Pertuzumab and Trastuzumab in Breast Cancer

Roisin Connolly, Jeffrey Pettit Leal, Lilja Solnes, Chiung Yu Huang, Ashley Carpenter, Katy Gaffney, Vandana Abramson, Lisa A. Carey, Minetta C. Liu, Mothaffar Rimawi, Jennifer Specht, Anna Maria Storniolo, Vicente Valero, Christos Vaklavas, Ian E. Krop, Eric P. Winer, Melissa Camp, Robert S. Miller, Antonio C Wolff, Ashley M Cimino-Mathews & 3 others Ben H. Park, Richard L. Wahl, Vered Stearns

Research output: Contribution to journalArticle

Abstract

PURPOSE: Predictive biomarkers to identify patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer who may benefit from targeted therapy alone are required. We hypothesized that early measurements of tumor maximum standardized uptake values corrected for lean body mass (SULmax) on [18F]fluorodeoxyglucose positron emission tomography/computed tomography would predict pathologic complete response (pCR) to neoadjuvant pertuzumab and trastuzumab (PT). PATIENTS AND METHODS: Patients with stage II/III, estrogen receptor-negative, HER2-positive breast cancer received four cycles of neoadjuvant PT. [18F]Fluorodeoxyglucose positron emission tomography/computed tomography was performed at baseline and 15 days after PT initiation (C1D15). Eighty evaluable patients were required to test the null hypothesis that the area under the curve of percentage of change in SULmax by C1D15 predicting pCR is less than or equal to 0.65, with a one-sided type I error rate of 10%. RESULTS: Eighty-eight women were enrolled (83 evaluable), and 85% (75 of 88) completed all four cycles of PT. pCR after PT alone was 34%. Receiver operating characteristic analysis yielded an area under the curve of 0.76 (90% CI, 0.67 to 0.85), which rejected the null hypothesis. Between patients who obtained pCR versus not, a significant difference in median percent reduction in SULmax by C1D15 was observed (63.8% v 33.5%; P < .001), an SULmax reduction greater than or equal to 40% was more prevalent (86% v 46%; P < .001; negative predictive value, 88%; positive predictive value, 49%), and a significant difference in median C1D15 SULmax (1.6 v 3.9; P < .001) and higher proportion of C1D15 SULmax less than or equal to 3 (93% v 38%; P < .001; negative predictive value, 94%; positive predictive value, 55%) were observed. CONCLUSION: Early changes in SULmax predict response to four cycles of PT in estrogen receptor-negative, HER2-positive breast cancer. Once optimized, this quantitative imaging strategy may facilitate a more tailored approach to therapy in this setting.

Original languageEnglish (US)
Pages (from-to)714-722
Number of pages9
JournalJournal of clinical oncology : official journal of the American Society of Clinical Oncology
Volume37
Issue number9
DOIs
StatePublished - Mar 20 2019

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Breast Neoplasms
Fluorodeoxyglucose F18
Estrogen Receptors
Area Under Curve
ROC Curve
Trastuzumab
pertuzumab
Biomarkers
Therapeutics
human ERBB2 protein
Neoplasms
Positron Emission Tomography Computed Tomography

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

TBCRC026 : Phase II Trial Correlating Standardized Uptake Value With Pathologic Complete Response to Pertuzumab and Trastuzumab in Breast Cancer. / Connolly, Roisin; Leal, Jeffrey Pettit; Solnes, Lilja; Huang, Chiung Yu; Carpenter, Ashley; Gaffney, Katy; Abramson, Vandana; Carey, Lisa A.; Liu, Minetta C.; Rimawi, Mothaffar; Specht, Jennifer; Storniolo, Anna Maria; Valero, Vicente; Vaklavas, Christos; Krop, Ian E.; Winer, Eric P.; Camp, Melissa; Miller, Robert S.; Wolff, Antonio C; Cimino-Mathews, Ashley M; Park, Ben H.; Wahl, Richard L.; Stearns, Vered.

In: Journal of clinical oncology : official journal of the American Society of Clinical Oncology, Vol. 37, No. 9, 20.03.2019, p. 714-722.

Research output: Contribution to journalArticle

Connolly, R, Leal, JP, Solnes, L, Huang, CY, Carpenter, A, Gaffney, K, Abramson, V, Carey, LA, Liu, MC, Rimawi, M, Specht, J, Storniolo, AM, Valero, V, Vaklavas, C, Krop, IE, Winer, EP, Camp, M, Miller, RS, Wolff, AC, Cimino-Mathews, AM, Park, BH, Wahl, RL & Stearns, V 2019, 'TBCRC026: Phase II Trial Correlating Standardized Uptake Value With Pathologic Complete Response to Pertuzumab and Trastuzumab in Breast Cancer', Journal of clinical oncology : official journal of the American Society of Clinical Oncology, vol. 37, no. 9, pp. 714-722. https://doi.org/10.1200/JCO.2018.78.7986
Connolly, Roisin ; Leal, Jeffrey Pettit ; Solnes, Lilja ; Huang, Chiung Yu ; Carpenter, Ashley ; Gaffney, Katy ; Abramson, Vandana ; Carey, Lisa A. ; Liu, Minetta C. ; Rimawi, Mothaffar ; Specht, Jennifer ; Storniolo, Anna Maria ; Valero, Vicente ; Vaklavas, Christos ; Krop, Ian E. ; Winer, Eric P. ; Camp, Melissa ; Miller, Robert S. ; Wolff, Antonio C ; Cimino-Mathews, Ashley M ; Park, Ben H. ; Wahl, Richard L. ; Stearns, Vered. / TBCRC026 : Phase II Trial Correlating Standardized Uptake Value With Pathologic Complete Response to Pertuzumab and Trastuzumab in Breast Cancer. In: Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2019 ; Vol. 37, No. 9. pp. 714-722.
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abstract = "PURPOSE: Predictive biomarkers to identify patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer who may benefit from targeted therapy alone are required. We hypothesized that early measurements of tumor maximum standardized uptake values corrected for lean body mass (SULmax) on [18F]fluorodeoxyglucose positron emission tomography/computed tomography would predict pathologic complete response (pCR) to neoadjuvant pertuzumab and trastuzumab (PT). PATIENTS AND METHODS: Patients with stage II/III, estrogen receptor-negative, HER2-positive breast cancer received four cycles of neoadjuvant PT. [18F]Fluorodeoxyglucose positron emission tomography/computed tomography was performed at baseline and 15 days after PT initiation (C1D15). Eighty evaluable patients were required to test the null hypothesis that the area under the curve of percentage of change in SULmax by C1D15 predicting pCR is less than or equal to 0.65, with a one-sided type I error rate of 10{\%}. RESULTS: Eighty-eight women were enrolled (83 evaluable), and 85{\%} (75 of 88) completed all four cycles of PT. pCR after PT alone was 34{\%}. Receiver operating characteristic analysis yielded an area under the curve of 0.76 (90{\%} CI, 0.67 to 0.85), which rejected the null hypothesis. Between patients who obtained pCR versus not, a significant difference in median percent reduction in SULmax by C1D15 was observed (63.8{\%} v 33.5{\%}; P < .001), an SULmax reduction greater than or equal to 40{\%} was more prevalent (86{\%} v 46{\%}; P < .001; negative predictive value, 88{\%}; positive predictive value, 49{\%}), and a significant difference in median C1D15 SULmax (1.6 v 3.9; P < .001) and higher proportion of C1D15 SULmax less than or equal to 3 (93{\%} v 38{\%}; P < .001; negative predictive value, 94{\%}; positive predictive value, 55{\%}) were observed. CONCLUSION: Early changes in SULmax predict response to four cycles of PT in estrogen receptor-negative, HER2-positive breast cancer. Once optimized, this quantitative imaging strategy may facilitate a more tailored approach to therapy in this setting.",
author = "Roisin Connolly and Leal, {Jeffrey Pettit} and Lilja Solnes and Huang, {Chiung Yu} and Ashley Carpenter and Katy Gaffney and Vandana Abramson and Carey, {Lisa A.} and Liu, {Minetta C.} and Mothaffar Rimawi and Jennifer Specht and Storniolo, {Anna Maria} and Vicente Valero and Christos Vaklavas and Krop, {Ian E.} and Winer, {Eric P.} and Melissa Camp and Miller, {Robert S.} and Wolff, {Antonio C} and Cimino-Mathews, {Ashley M} and Park, {Ben H.} and Wahl, {Richard L.} and Vered Stearns",
year = "2019",
month = "3",
day = "20",
doi = "10.1200/JCO.2018.78.7986",
language = "English (US)",
volume = "37",
pages = "714--722",
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publisher = "American Society of Clinical Oncology",
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}

TY - JOUR

T1 - TBCRC026

T2 - Phase II Trial Correlating Standardized Uptake Value With Pathologic Complete Response to Pertuzumab and Trastuzumab in Breast Cancer

AU - Connolly, Roisin

AU - Leal, Jeffrey Pettit

AU - Solnes, Lilja

AU - Huang, Chiung Yu

AU - Carpenter, Ashley

AU - Gaffney, Katy

AU - Abramson, Vandana

AU - Carey, Lisa A.

AU - Liu, Minetta C.

AU - Rimawi, Mothaffar

AU - Specht, Jennifer

AU - Storniolo, Anna Maria

AU - Valero, Vicente

AU - Vaklavas, Christos

AU - Krop, Ian E.

AU - Winer, Eric P.

AU - Camp, Melissa

AU - Miller, Robert S.

AU - Wolff, Antonio C

AU - Cimino-Mathews, Ashley M

AU - Park, Ben H.

AU - Wahl, Richard L.

AU - Stearns, Vered

PY - 2019/3/20

Y1 - 2019/3/20

N2 - PURPOSE: Predictive biomarkers to identify patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer who may benefit from targeted therapy alone are required. We hypothesized that early measurements of tumor maximum standardized uptake values corrected for lean body mass (SULmax) on [18F]fluorodeoxyglucose positron emission tomography/computed tomography would predict pathologic complete response (pCR) to neoadjuvant pertuzumab and trastuzumab (PT). PATIENTS AND METHODS: Patients with stage II/III, estrogen receptor-negative, HER2-positive breast cancer received four cycles of neoadjuvant PT. [18F]Fluorodeoxyglucose positron emission tomography/computed tomography was performed at baseline and 15 days after PT initiation (C1D15). Eighty evaluable patients were required to test the null hypothesis that the area under the curve of percentage of change in SULmax by C1D15 predicting pCR is less than or equal to 0.65, with a one-sided type I error rate of 10%. RESULTS: Eighty-eight women were enrolled (83 evaluable), and 85% (75 of 88) completed all four cycles of PT. pCR after PT alone was 34%. Receiver operating characteristic analysis yielded an area under the curve of 0.76 (90% CI, 0.67 to 0.85), which rejected the null hypothesis. Between patients who obtained pCR versus not, a significant difference in median percent reduction in SULmax by C1D15 was observed (63.8% v 33.5%; P < .001), an SULmax reduction greater than or equal to 40% was more prevalent (86% v 46%; P < .001; negative predictive value, 88%; positive predictive value, 49%), and a significant difference in median C1D15 SULmax (1.6 v 3.9; P < .001) and higher proportion of C1D15 SULmax less than or equal to 3 (93% v 38%; P < .001; negative predictive value, 94%; positive predictive value, 55%) were observed. CONCLUSION: Early changes in SULmax predict response to four cycles of PT in estrogen receptor-negative, HER2-positive breast cancer. Once optimized, this quantitative imaging strategy may facilitate a more tailored approach to therapy in this setting.

AB - PURPOSE: Predictive biomarkers to identify patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer who may benefit from targeted therapy alone are required. We hypothesized that early measurements of tumor maximum standardized uptake values corrected for lean body mass (SULmax) on [18F]fluorodeoxyglucose positron emission tomography/computed tomography would predict pathologic complete response (pCR) to neoadjuvant pertuzumab and trastuzumab (PT). PATIENTS AND METHODS: Patients with stage II/III, estrogen receptor-negative, HER2-positive breast cancer received four cycles of neoadjuvant PT. [18F]Fluorodeoxyglucose positron emission tomography/computed tomography was performed at baseline and 15 days after PT initiation (C1D15). Eighty evaluable patients were required to test the null hypothesis that the area under the curve of percentage of change in SULmax by C1D15 predicting pCR is less than or equal to 0.65, with a one-sided type I error rate of 10%. RESULTS: Eighty-eight women were enrolled (83 evaluable), and 85% (75 of 88) completed all four cycles of PT. pCR after PT alone was 34%. Receiver operating characteristic analysis yielded an area under the curve of 0.76 (90% CI, 0.67 to 0.85), which rejected the null hypothesis. Between patients who obtained pCR versus not, a significant difference in median percent reduction in SULmax by C1D15 was observed (63.8% v 33.5%; P < .001), an SULmax reduction greater than or equal to 40% was more prevalent (86% v 46%; P < .001; negative predictive value, 88%; positive predictive value, 49%), and a significant difference in median C1D15 SULmax (1.6 v 3.9; P < .001) and higher proportion of C1D15 SULmax less than or equal to 3 (93% v 38%; P < .001; negative predictive value, 94%; positive predictive value, 55%) were observed. CONCLUSION: Early changes in SULmax predict response to four cycles of PT in estrogen receptor-negative, HER2-positive breast cancer. Once optimized, this quantitative imaging strategy may facilitate a more tailored approach to therapy in this setting.

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U2 - 10.1200/JCO.2018.78.7986

DO - 10.1200/JCO.2018.78.7986

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JO - Journal of Clinical Oncology

JF - Journal of Clinical Oncology

SN - 0732-183X

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