Impact of biomarkers on clinical trial risk in breast cancer

Jayson L. Parker, Nadia Lushina, Prabjot S. Bal, Teresa Petrella, Rebecca Dent, Gilberto Lopes

Research output: Contribution to journalArticle

Abstract

We determined the success rate of new drug approval by the US FDA in two breast cancer indications, one of which used a biomarker. This allowed us to assess if biomarkers improved clinical trial risk in breast cancer. We performed a retrospective screening of industry-sponsored drug development programs registered on clinicaltrials.gov from 1998 to 2012 for HER2-positive patients compared to patients that had either failed or had been exposed to anthracycline or taxane, whose first phase I in this indication occurred no earlier than 1998. Compounds not registered on clinicaltrials.gov and studied exclusively outside the US were excluded. Twenty-nine drugs for HER2-positive patients and 28 drugs for anthracycline/taxane-exposed patients met our screening criteria. The overall success rate of new drug development in anthracycline/taxane patients was only 15 %, while in HER2-positive patients it was 23 %. However, HER2-targeted therapies underperformed compared to broad acting agents. The cost for clinical trial testing alone, when adjusted for the risk of failure, for HER2-positive breast cancer patients was $199 million, significantly lower than the cost of $274 million for anthracycline/taxane-experienced patients. The use of a validated biomarker, such as HER2, reduced clinical trial risk by as much as 50 % resulting in cost savings of 27 % in advanced and metastatic breast cancer. However, these data have to be evaluated in a context in which studies combining a novel drug with a novel biomarker not yet recognized by the FDA may actually increase clinical trial risk.

Original languageEnglish (US)
Pages (from-to)179-185
Number of pages7
JournalBreast Cancer Research and Treatment
Volume136
Issue number1
DOIs
StatePublished - Nov 2012

Fingerprint

Biomarkers
Clinical Trials
Breast Neoplasms
Anthracyclines
Pharmaceutical Preparations
Drug Approval
Costs and Cost Analysis
Cost Savings
Drug Industry
taxane

Keywords

  • Biomarker
  • Clinical trial
  • HER2
  • Metastatic breast cancer
  • Pharmacogenomics
  • Risk

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Parker, J. L., Lushina, N., Bal, P. S., Petrella, T., Dent, R., & Lopes, G. (2012). Impact of biomarkers on clinical trial risk in breast cancer. Breast Cancer Research and Treatment, 136(1), 179-185. https://doi.org/10.1007/s10549-012-2247-6

Impact of biomarkers on clinical trial risk in breast cancer. / Parker, Jayson L.; Lushina, Nadia; Bal, Prabjot S.; Petrella, Teresa; Dent, Rebecca; Lopes, Gilberto.

In: Breast Cancer Research and Treatment, Vol. 136, No. 1, 11.2012, p. 179-185.

Research output: Contribution to journalArticle

Parker, JL, Lushina, N, Bal, PS, Petrella, T, Dent, R & Lopes, G 2012, 'Impact of biomarkers on clinical trial risk in breast cancer', Breast Cancer Research and Treatment, vol. 136, no. 1, pp. 179-185. https://doi.org/10.1007/s10549-012-2247-6
Parker, Jayson L. ; Lushina, Nadia ; Bal, Prabjot S. ; Petrella, Teresa ; Dent, Rebecca ; Lopes, Gilberto. / Impact of biomarkers on clinical trial risk in breast cancer. In: Breast Cancer Research and Treatment. 2012 ; Vol. 136, No. 1. pp. 179-185.
@article{6cf4f9fcf3c94080a2a54110f0614ed8,
title = "Impact of biomarkers on clinical trial risk in breast cancer",
abstract = "We determined the success rate of new drug approval by the US FDA in two breast cancer indications, one of which used a biomarker. This allowed us to assess if biomarkers improved clinical trial risk in breast cancer. We performed a retrospective screening of industry-sponsored drug development programs registered on clinicaltrials.gov from 1998 to 2012 for HER2-positive patients compared to patients that had either failed or had been exposed to anthracycline or taxane, whose first phase I in this indication occurred no earlier than 1998. Compounds not registered on clinicaltrials.gov and studied exclusively outside the US were excluded. Twenty-nine drugs for HER2-positive patients and 28 drugs for anthracycline/taxane-exposed patients met our screening criteria. The overall success rate of new drug development in anthracycline/taxane patients was only 15 {\%}, while in HER2-positive patients it was 23 {\%}. However, HER2-targeted therapies underperformed compared to broad acting agents. The cost for clinical trial testing alone, when adjusted for the risk of failure, for HER2-positive breast cancer patients was $199 million, significantly lower than the cost of $274 million for anthracycline/taxane-experienced patients. The use of a validated biomarker, such as HER2, reduced clinical trial risk by as much as 50 {\%} resulting in cost savings of 27 {\%} in advanced and metastatic breast cancer. However, these data have to be evaluated in a context in which studies combining a novel drug with a novel biomarker not yet recognized by the FDA may actually increase clinical trial risk.",
keywords = "Biomarker, Clinical trial, HER2, Metastatic breast cancer, Pharmacogenomics, Risk",
author = "Parker, {Jayson L.} and Nadia Lushina and Bal, {Prabjot S.} and Teresa Petrella and Rebecca Dent and Gilberto Lopes",
year = "2012",
month = "11",
doi = "10.1007/s10549-012-2247-6",
language = "English (US)",
volume = "136",
pages = "179--185",
journal = "Breast Cancer Research and Treatment",
issn = "0167-6806",
publisher = "Springer New York",
number = "1",

}

TY - JOUR

T1 - Impact of biomarkers on clinical trial risk in breast cancer

AU - Parker, Jayson L.

AU - Lushina, Nadia

AU - Bal, Prabjot S.

AU - Petrella, Teresa

AU - Dent, Rebecca

AU - Lopes, Gilberto

PY - 2012/11

Y1 - 2012/11

N2 - We determined the success rate of new drug approval by the US FDA in two breast cancer indications, one of which used a biomarker. This allowed us to assess if biomarkers improved clinical trial risk in breast cancer. We performed a retrospective screening of industry-sponsored drug development programs registered on clinicaltrials.gov from 1998 to 2012 for HER2-positive patients compared to patients that had either failed or had been exposed to anthracycline or taxane, whose first phase I in this indication occurred no earlier than 1998. Compounds not registered on clinicaltrials.gov and studied exclusively outside the US were excluded. Twenty-nine drugs for HER2-positive patients and 28 drugs for anthracycline/taxane-exposed patients met our screening criteria. The overall success rate of new drug development in anthracycline/taxane patients was only 15 %, while in HER2-positive patients it was 23 %. However, HER2-targeted therapies underperformed compared to broad acting agents. The cost for clinical trial testing alone, when adjusted for the risk of failure, for HER2-positive breast cancer patients was $199 million, significantly lower than the cost of $274 million for anthracycline/taxane-experienced patients. The use of a validated biomarker, such as HER2, reduced clinical trial risk by as much as 50 % resulting in cost savings of 27 % in advanced and metastatic breast cancer. However, these data have to be evaluated in a context in which studies combining a novel drug with a novel biomarker not yet recognized by the FDA may actually increase clinical trial risk.

AB - We determined the success rate of new drug approval by the US FDA in two breast cancer indications, one of which used a biomarker. This allowed us to assess if biomarkers improved clinical trial risk in breast cancer. We performed a retrospective screening of industry-sponsored drug development programs registered on clinicaltrials.gov from 1998 to 2012 for HER2-positive patients compared to patients that had either failed or had been exposed to anthracycline or taxane, whose first phase I in this indication occurred no earlier than 1998. Compounds not registered on clinicaltrials.gov and studied exclusively outside the US were excluded. Twenty-nine drugs for HER2-positive patients and 28 drugs for anthracycline/taxane-exposed patients met our screening criteria. The overall success rate of new drug development in anthracycline/taxane patients was only 15 %, while in HER2-positive patients it was 23 %. However, HER2-targeted therapies underperformed compared to broad acting agents. The cost for clinical trial testing alone, when adjusted for the risk of failure, for HER2-positive breast cancer patients was $199 million, significantly lower than the cost of $274 million for anthracycline/taxane-experienced patients. The use of a validated biomarker, such as HER2, reduced clinical trial risk by as much as 50 % resulting in cost savings of 27 % in advanced and metastatic breast cancer. However, these data have to be evaluated in a context in which studies combining a novel drug with a novel biomarker not yet recognized by the FDA may actually increase clinical trial risk.

KW - Biomarker

KW - Clinical trial

KW - HER2

KW - Metastatic breast cancer

KW - Pharmacogenomics

KW - Risk

UR - http://www.scopus.com/inward/record.url?scp=84867861298&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84867861298&partnerID=8YFLogxK

U2 - 10.1007/s10549-012-2247-6

DO - 10.1007/s10549-012-2247-6

M3 - Article

C2 - 23007573

AN - SCOPUS:84867861298

VL - 136

SP - 179

EP - 185

JO - Breast Cancer Research and Treatment

JF - Breast Cancer Research and Treatment

SN - 0167-6806

IS - 1

ER -