Department of Biology, University of Toronto, Mississauga, ON, Canada.
Breast Cancer Res Treat. 2012 Nov;136(1):179-85. doi: 10.1007/s10549-012-2247-6. Epub 2012 Sep 25.
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.
我们确定了美国 FDA 在两种乳腺癌适应症新药批准的成功率，其中一种使用了生物标志物。这使我们能够评估生物标志物是否改善了乳腺癌临床试验的风险。我们对 1998 年至 2012 年期间在 clinicaltrials.gov 上注册的行业赞助药物开发项目进行了回顾性筛选，比较了 HER2 阳性患者与那些已经失败或已经接受蒽环类或紫杉烷治疗的患者，其在该适应症的首次 I 期临床试验不早于 1998 年。不注册于 clinicaltrials.gov 且仅在美国境外研究的化合物被排除在外。符合我们筛选标准的 HER2 阳性患者的药物有 29 种，蒽环类/紫杉烷暴露患者的药物有 28 种。蒽环类/紫杉烷暴露患者新药开发的总体成功率仅为 15%，而 HER2 阳性患者的成功率为 23%。然而，HER2 靶向治疗的表现逊于广泛作用的药物。考虑到失败的风险，HER2 阳性乳腺癌患者的临床试验测试费用为 1.99 亿美元，远低于蒽环类/紫杉烷经验丰富患者的 2.74 亿美元。使用经过验证的生物标志物（如 HER2）可降低临床试验风险高达 50%，从而在晚期和转移性乳腺癌中节省 27%的成本。然而，这些数据必须在这样一种背景下进行评估，即在研究中，将一种新药与一种尚未得到 FDA 认可的新生物标志物相结合的研究可能实际上会增加临床试验的风险。
