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Title: The Clinical Development of Molecularly Targeted Agents in Combination With Radiation Therapy: A Pharmaceutical Perspective

Abstract

Summary: This paper explores historical and current roles of pharmaceutical industry sponsorship of clinical trials testing radiation therapy combinations with molecularly targeted agents and attempts to identify potential solutions to expediting further combination studies. An analysis of clinical trials involving a combination of radiation therapy and novel cancer therapies was performed. Ongoing and completed trials were identified by searching the (clinicaltrials.gov) Web site, in the first instance, with published trials of drugs of interest identified through American Society of Clinical Oncology, European CanCer Organisation/European Society for Medical Oncology, American Society for Radiation Oncology/European Society for Therapeutic Radiology and Oncology, and PubMed databases and then cross-correlated with (clinicaltrials.gov) protocols. We examined combination trials involving radiation therapy with novel agents and determined their distribution by tumor type, predominant molecular mechanisms examined in combination to date, timing of initiation of trials relative to a novel agent's primary development, and source of sponsorship of such trials. A total of 564 studies of targeted agents in combination with radiation therapy were identified with or without concomitant chemotherapy. Most studies were in phase I/II development, with only 36 trials in phase III. The tumor site most frequently studied was head and neck (26%), followed by non-smallmore » cell lung cancer. Pharmaceutical companies were the sponsors of 33% of studies overall and provided support for only 16% of phase III studies. In terms of pharmaceutical sponsorship, Genentech was the most active sponsor of radiation therapy combinations (22%), followed by AstraZeneca (14%). Most radiation therapy combination trials do not appear to be initiated until after drug approval. In phase III studies, the most common (58%) primary endpoint was overall survival. Collectively, this analysis suggests that such trials are not given priority by pharmaceutical companies. The potential reasons for this and some challenges and possible solutions are discussed.« less

Authors:
 [1];  [1];  [2];  [1];  [3];  [2]
  1. Global Medicines Development, AstraZeneca, Alderley Park, Macclesfield, Cheshire (United Kingdom)
  2. Innovative Medicines, AstraZeneca, Alderley Park, Macclesfield, Cheshire (United Kingdom)
  3. Yellow Delaney Communications Ltd, Wilmslow, Cheshire (United Kingdom)
Publication Date:
OSTI Identifier:
22149618
Resource Type:
Journal Article
Journal Name:
International Journal of Radiation Oncology, Biology and Physics
Additional Journal Information:
Journal Volume: 84; Journal Issue: 4; Other Information: Copyright (c) 2012 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0360-3016
Country of Publication:
United States
Language:
English
Subject:
62 RADIOLOGY AND NUCLEAR MEDICINE; CHEMOTHERAPY; CLINICAL TRIALS; DISTRIBUTION; DRUGS; HEAD; LUNGS; NECK; NEOPLASMS; RADIOTHERAPY

Citation Formats

Ataman, Ozlem U., E-mail: ouataman@hotmail.com, Sambrook, Sally J., Wilks, Chris, Lloyd, Andrew, Taylor, Amanda E., and Wedge, Stephen R. The Clinical Development of Molecularly Targeted Agents in Combination With Radiation Therapy: A Pharmaceutical Perspective. United States: N. p., 2012. Web. doi:10.1016/J.IJROBP.2012.05.019.
Ataman, Ozlem U., E-mail: ouataman@hotmail.com, Sambrook, Sally J., Wilks, Chris, Lloyd, Andrew, Taylor, Amanda E., & Wedge, Stephen R. The Clinical Development of Molecularly Targeted Agents in Combination With Radiation Therapy: A Pharmaceutical Perspective. United States. doi:10.1016/J.IJROBP.2012.05.019.
Ataman, Ozlem U., E-mail: ouataman@hotmail.com, Sambrook, Sally J., Wilks, Chris, Lloyd, Andrew, Taylor, Amanda E., and Wedge, Stephen R. Thu . "The Clinical Development of Molecularly Targeted Agents in Combination With Radiation Therapy: A Pharmaceutical Perspective". United States. doi:10.1016/J.IJROBP.2012.05.019.
@article{osti_22149618,
title = {The Clinical Development of Molecularly Targeted Agents in Combination With Radiation Therapy: A Pharmaceutical Perspective},
author = {Ataman, Ozlem U., E-mail: ouataman@hotmail.com and Sambrook, Sally J. and Wilks, Chris and Lloyd, Andrew and Taylor, Amanda E. and Wedge, Stephen R.},
abstractNote = {Summary: This paper explores historical and current roles of pharmaceutical industry sponsorship of clinical trials testing radiation therapy combinations with molecularly targeted agents and attempts to identify potential solutions to expediting further combination studies. An analysis of clinical trials involving a combination of radiation therapy and novel cancer therapies was performed. Ongoing and completed trials were identified by searching the (clinicaltrials.gov) Web site, in the first instance, with published trials of drugs of interest identified through American Society of Clinical Oncology, European CanCer Organisation/European Society for Medical Oncology, American Society for Radiation Oncology/European Society for Therapeutic Radiology and Oncology, and PubMed databases and then cross-correlated with (clinicaltrials.gov) protocols. We examined combination trials involving radiation therapy with novel agents and determined their distribution by tumor type, predominant molecular mechanisms examined in combination to date, timing of initiation of trials relative to a novel agent's primary development, and source of sponsorship of such trials. A total of 564 studies of targeted agents in combination with radiation therapy were identified with or without concomitant chemotherapy. Most studies were in phase I/II development, with only 36 trials in phase III. The tumor site most frequently studied was head and neck (26%), followed by non-small cell lung cancer. Pharmaceutical companies were the sponsors of 33% of studies overall and provided support for only 16% of phase III studies. In terms of pharmaceutical sponsorship, Genentech was the most active sponsor of radiation therapy combinations (22%), followed by AstraZeneca (14%). Most radiation therapy combination trials do not appear to be initiated until after drug approval. In phase III studies, the most common (58%) primary endpoint was overall survival. Collectively, this analysis suggests that such trials are not given priority by pharmaceutical companies. The potential reasons for this and some challenges and possible solutions are discussed.},
doi = {10.1016/J.IJROBP.2012.05.019},
journal = {International Journal of Radiation Oncology, Biology and Physics},
issn = {0360-3016},
number = 4,
volume = 84,
place = {United States},
year = {2012},
month = {11}
}