Global Medicines Development, AstraZeneca, Alderley Park, Macclesfield, Cheshire, United Kingdom.
Int J Radiat Oncol Biol Phys. 2012 Nov 15;84(4):e447-54. doi: 10.1016/j.ijrobp.2012.05.019. Epub 2012 Jul 20.
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.
本文探讨了制药行业在临床试验中对放射治疗联合分子靶向药物的历史和当前作用，并试图确定加速进一步联合研究的潜在解决方案。通过搜索 clinicaltrials.gov 网站，对涉及放射治疗与新型癌症疗法联合的临床试验进行了分析。首先，通过美国临床肿瘤学会、欧洲癌症组织/欧洲肿瘤内科学会、美国放射肿瘤学会/欧洲放射治疗与肿瘤学会以及 PubMed 数据库，确定了正在进行和已完成的试验，然后与 clinicaltrials.gov 方案进行交叉核对。我们检查了涉及放射治疗与新型药物联合的联合试验，并根据肿瘤类型、迄今为止联合检查的主要分子机制、试验启动相对于新型药物主要开发的时间以及此类试验的赞助来源对其进行了分类。共确定了 564 项联合放射治疗和新型药物的靶向药物研究，无论是否联合化疗。大多数研究处于 I/II 期开发阶段，只有 36 项研究处于 III 期。研究最多的肿瘤部位是头颈部（26%），其次是非小细胞肺癌。制药公司总体上是 33%研究的赞助商，并仅为 16%的 III 期研究提供支持。就制药赞助而言，基因泰克是放射治疗联合研究最活跃的赞助商（22%），其次是阿斯利康（14%）。大多数放射治疗联合试验似乎直到药物批准后才开始。在 III 期研究中，最常见的（58%）主要终点是总生存期。总体而言，这项分析表明，制药公司对此类试验并不重视。讨论了这种情况的潜在原因以及一些挑战和可能的解决方案。
