Investigating the impact of target lesion selection on drug effect evaluation and tumour growth rate determination using tumour growth inhibition modelsCitation formats

  • External authors:
  • Aurélie Lombard
  • Sonya C Chapman
  • Ivelina Gueorguieva

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Investigating the impact of target lesion selection on drug effect evaluation and tumour growth rate determination using tumour growth inhibition models : example of malignant pleural mesothelioma patients treated with cisplatin alone or in combination with pemetrexed. / Lombard, Aurélie; Mistry, Hitesh; Chapman, Sonya C; Gueorguieva, Ivelina; Aarons, Leon; Ogungbenro, Kayode.

In: European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences, Vol. 161, 105781, 01.06.2021.

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@article{4de80f7303cf4007b73fb97375f17f71,
title = "Investigating the impact of target lesion selection on drug effect evaluation and tumour growth rate determination using tumour growth inhibition models: example of malignant pleural mesothelioma patients treated with cisplatin alone or in combination with pemetrexed",
abstract = "In the last update of the RECIST criteria in 2009, it was proposed that the number of target lesions to be followed over time for response-to-treatment assessment be reduced from 10 to 5 lesions maximum, with up to 2 per organ. We explored the impact of reducing the number of target lesion on the assessment of drug effect in a randomised phase III clinical trial using a tumour growth inhibition (TGI) model. Tumour size measurements from 441 (out of 456) patients were used to build two datasets for which observations were the sum of longest diameters of all measurable lesions (ALL dataset) or following the RECIST 1.1 recommendations (R1.1 dataset). TGI models incorporating a categorical covariate for treatment group or a pharmacokinetic metric (i.e. dose; simulated area under the curve) were used to describe the longitudinal tumour size kinetics. Drug exposure was not superior to treatment group at describing drug effect. ALL and R1.1 individual estimates of drug effect appeared to be strongly correlated (r2=0.88). Including pharmacokinetic metrics in TGI models should be conducted carefully when no pharmacokinetic samples are available. Reducing the number of target lesion did not seem to compromise the determination of drug effect using TGI models.",
keywords = "Chemotherapy, Malignant pleural mesothelioma, Modelling, Target lesion selection",
author = "Aur{\'e}lie Lombard and Hitesh Mistry and Chapman, {Sonya C} and Ivelina Gueorguieva and Leon Aarons and Kayode Ogungbenro",
note = "Funding Information: Sonya C. Chapman and Ivelina Gueorguieva are employees and shareholders of Eli Lilly & Company at the time the work was done. Aurelie Lombard is a PhD student sponsored by the Centre for Applied Pharmacokinetic Research (CAPKR) and the Division of Pharmacy and Optometry, University of Manchester (CAPKR is supported by the following consortium members; Eli Lilly, Certara, Merck, Genentech, Takeda, Johnson&Johnson, GSK, AbbVie and Merck Serono). Kayode Ogungbenro and Leon Aarons are members of CAPKR. Publisher Copyright: {\textcopyright} 2021 Elsevier B.V. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.",
year = "2021",
month = jun,
day = "1",
doi = "10.1016/j.ejps.2021.105781",
language = "English",
volume = "161",
journal = "European Journal of Pharmaceutical Sciences",
issn = "0928-0987",
publisher = "Elsevier BV",

}

RIS

TY - JOUR

T1 - Investigating the impact of target lesion selection on drug effect evaluation and tumour growth rate determination using tumour growth inhibition models

T2 - example of malignant pleural mesothelioma patients treated with cisplatin alone or in combination with pemetrexed

AU - Lombard, Aurélie

AU - Mistry, Hitesh

AU - Chapman, Sonya C

AU - Gueorguieva, Ivelina

AU - Aarons, Leon

AU - Ogungbenro, Kayode

N1 - Funding Information: Sonya C. Chapman and Ivelina Gueorguieva are employees and shareholders of Eli Lilly & Company at the time the work was done. Aurelie Lombard is a PhD student sponsored by the Centre for Applied Pharmacokinetic Research (CAPKR) and the Division of Pharmacy and Optometry, University of Manchester (CAPKR is supported by the following consortium members; Eli Lilly, Certara, Merck, Genentech, Takeda, Johnson&Johnson, GSK, AbbVie and Merck Serono). Kayode Ogungbenro and Leon Aarons are members of CAPKR. Publisher Copyright: © 2021 Elsevier B.V. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.

PY - 2021/6/1

Y1 - 2021/6/1

N2 - In the last update of the RECIST criteria in 2009, it was proposed that the number of target lesions to be followed over time for response-to-treatment assessment be reduced from 10 to 5 lesions maximum, with up to 2 per organ. We explored the impact of reducing the number of target lesion on the assessment of drug effect in a randomised phase III clinical trial using a tumour growth inhibition (TGI) model. Tumour size measurements from 441 (out of 456) patients were used to build two datasets for which observations were the sum of longest diameters of all measurable lesions (ALL dataset) or following the RECIST 1.1 recommendations (R1.1 dataset). TGI models incorporating a categorical covariate for treatment group or a pharmacokinetic metric (i.e. dose; simulated area under the curve) were used to describe the longitudinal tumour size kinetics. Drug exposure was not superior to treatment group at describing drug effect. ALL and R1.1 individual estimates of drug effect appeared to be strongly correlated (r2=0.88). Including pharmacokinetic metrics in TGI models should be conducted carefully when no pharmacokinetic samples are available. Reducing the number of target lesion did not seem to compromise the determination of drug effect using TGI models.

AB - In the last update of the RECIST criteria in 2009, it was proposed that the number of target lesions to be followed over time for response-to-treatment assessment be reduced from 10 to 5 lesions maximum, with up to 2 per organ. We explored the impact of reducing the number of target lesion on the assessment of drug effect in a randomised phase III clinical trial using a tumour growth inhibition (TGI) model. Tumour size measurements from 441 (out of 456) patients were used to build two datasets for which observations were the sum of longest diameters of all measurable lesions (ALL dataset) or following the RECIST 1.1 recommendations (R1.1 dataset). TGI models incorporating a categorical covariate for treatment group or a pharmacokinetic metric (i.e. dose; simulated area under the curve) were used to describe the longitudinal tumour size kinetics. Drug exposure was not superior to treatment group at describing drug effect. ALL and R1.1 individual estimates of drug effect appeared to be strongly correlated (r2=0.88). Including pharmacokinetic metrics in TGI models should be conducted carefully when no pharmacokinetic samples are available. Reducing the number of target lesion did not seem to compromise the determination of drug effect using TGI models.

KW - Chemotherapy

KW - Malignant pleural mesothelioma

KW - Modelling

KW - Target lesion selection

U2 - 10.1016/j.ejps.2021.105781

DO - 10.1016/j.ejps.2021.105781

M3 - Article

C2 - 33667665

VL - 161

JO - European Journal of Pharmaceutical Sciences

JF - European Journal of Pharmaceutical Sciences

SN - 0928-0987

M1 - 105781

ER -