Office of Oncologic Diseases, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland, USA.
Oncologist. 2020 Apr;25(4):348-354. doi: 10.1634/theoncologist.2019-0653. Epub 2019 Dec 17.
We examined how often new serious safety signals were identified by the U.S. Food and Drug Administration within the first 2 years after approval for new molecular entities (NMEs) for treatment of cancer that required specific regulatory actions described here.
We identified, for all NMEs approved for treatment of cancer or malignant hematology indications between 2010 and 2016, substantial safety-related changes within the first 2 years after approval, which included a new Boxed Warning or Warning and Precaution; requirement for (or modification of existing) Risk Evaluation and Mitigation Strategies (REMS); and withdrawal from the market because of safety concerns.
Fifty-five NMEs were approved between 2010 and 2016: 32 (58%) under regular approval (RA) and 23 (42%) under accelerated approval (AA). Of these 55 NMEs, 9 (16%) had substantial safety-related changes after approval. Across all 55 NMEs, one was temporarily withdrawn from the market for safety reasons (1.8%); one (1.8%) required a new REMS; nine required labeling revisions-new Boxed Warnings were required for two NMEs (3.6%), and new Warnings and Precautions subsections were required for eight (14.6%). One drug (ponatinib) was responsible for several of the substantial safety-related changes (withdrawal, REMS, Boxed Warnings). One of 32 NMEs approved under RA required a new Warning and Precaution, whereas 7 of 23 NMEs approved under AA had substantial safety-related changes in the first 2 years after approval.
Based on our analysis we conclude that although there was a greater incidence of substantial safety-related changes to AA drugs versus RA drugs, the majority of these were changes to the Warnings and Precautions and did not substantially alter the benefit-risk profile of the drug.
The majority of new cancer drugs (84%) approved in the U.S. do not have new substantial safety information being added to the label within the first 2 years of approval. Unprecedented efficacy seen in contemporary cancer drug development has led to early availability of effective cancer therapies based on large effects in smaller populations. More limited premarket safety data require diligent postmarketing safety surveillance as we continue to learn and update drug labeling throughout the product lifecycle.
我们研究了在新分子实体（NME）批准用于癌症治疗后的头 2 年内，美国食品和药物管理局（FDA）识别新的严重安全信号的频率，这些 NME 需采取此处描述的特定监管措施。
我们确定了 2010 年至 2016 年间所有批准用于治疗癌症或恶性血液病的 NME，在批准后 2 年内发生了重大安全相关变化，包括新的黑框警告或警告和注意事项；要求（或修改现有）风险评估和缓解策略（REMS）；以及因安全问题撤出市场。
2010 年至 2016 年期间批准了 55 个 NME：32 个（58%）采用常规批准（RA），23 个（42%）采用加速批准（AA）。在这 55 个 NME 中，有 9 个（16%）在批准后发生了重大安全相关变化。在所有 55 个 NME 中，有 1 个因安全原因暂时撤出市场（1.8%）；1 个（1.8%）需要新的 REMS；9 个需要标签修订-2 个 NME 需要新的黑框警告（3.6%），8 个需要新的警告和注意事项小节（14.6%）。一种药物（ponatinib）导致了几种重大安全相关变化（撤出市场、REMS、黑框警告）。在 RA 下批准的 32 个 NME 中有 1 个需要新的警告和注意事项，而在 AA 下批准的 23 个 NME 中有 7 个在批准后 2 年内发生了重大安全相关变化。
根据我们的分析，我们得出结论，尽管加速批准的药物发生重大安全相关变化的发生率高于常规批准的药物，但这些变化大多是对警告和注意事项的更改，并没有实质性地改变药物的风险收益状况。
美国批准的大多数新癌症药物（84%）在批准后的头 2 年内没有新的重大安全信息添加到标签中。在当代癌症药物开发中，前所未有的疗效导致了基于较小人群中较大影响的有效癌症治疗方法的早期应用。由于在整个产品生命周期中继续学习和更新药物标签，上市前安全性数据的局限性要求进行更严格的上市后安全性监测。
