JCO：請高度警惕，眾多抗癌藥物的毒副作用尚未真正搞清

美國《臨床腫瘤學雜誌》2018年4月11日在線先發

2006年至2016年美國食品和藥物管理局批准的癌症藥物上市後不論有無隨機對照試驗支持的藥品說明書修訂

目的

癌症藥物經食品和藥物管理局批准後，對其適應症、劑量和相關毒性的修改常見。目前還不清楚沒有隨機對照試驗（RCT）支持的獲批藥物是否會影響藥品說明書的這類修改。

方法

我們在Drugs@FDA網站上檢索了2006年1月至2016年12月期間批准的用於實體瘤的新葯適應症。我們從藥品說明書上收集了自2017年10月批准的藥物研究特點、監管途徑和說明書修訂信息，若藥物說明中有這種界定的修訂信息，則考慮為說明書修訂有重大調整。我們採用邏輯回歸分析，對有隨機對照試驗支持的適應症和沒有隨機對照試驗支持的適應症進行了比較，用Benjamini-Hochberg錯誤發現率方法對多種情況加以校正。

結果

我們甄別出59種藥物，有109個實體腫瘤適應症。其中17個適應症（15.6％）沒有隨機對照試驗支持，且隨時間推移適應症未變。沒有隨機對照試驗支持的適應症可能更需要伴隨診斷檢測（比值比[OR]，3.90；P=0.02）、更需要納入替代終點作為主要終點（OR，7.88；P

結論

起初沒有隨機對照試驗支持的癌症藥物的適應症，上市後對藥物安全性說明的修訂更多。衛生專業人員在開具沒有隨機對照試驗支持而獲批的藥物處方時，應當警惕尚不清楚的不良事件。

《桓興醫訊》孟祥志

Postmarketing Modifications of Drug Labels for Cancer Drugs Approved bythe US Food and Drug Administration Between 2006 and 2016 With and WithoutSupporting Randomized Controlled Trials

Daniel Shepshelovich, Ariadna Tibau, Hadar Goldvaser, Consolación Molto, Alberto Ocana, Bostjan Seruga...Show More

Purpose

Modifications in cancer drug indications, dosing, and related toxicities after Food and Drug Administration approval are common. It is unclear whether drug approval without a supporting randomized controlled trial (RCT) influences the probability of such modifications.

Methods

We searched the Drugs@FDA Web site for new drug indications for solid tumors approved between January 2006 and December 2016. Study characteristics, regulatory pathways, and label modifications from approval to October 2017 were collected from drug labels. Label modifications were considered to be major if defined as such in the drug label. Indications approved with and without supporting RCTs were compared using logistic regression. The Benjamini-Hochberg false discovery rate method was used to adjust for multiplicity.

Results

We identified 59 individual drugs for 109 solid tumor indications. Of these, 17 indications (15.6%) were not supported by an RCT, with no change over time. Indications not supported by RCTs were more likely to require companion diagnostic tests (odds ratio [OR], 3.90; P = .02), to include surrogate end points as primary outcomes (OR, 7.88; P

Conclusion

Cancer drug indications not supported initially by RCTs are associated with more postmarketing safety-related label modifications. Health care professionals should be vigilant for unrecognized adverse effects when prescribing drugs approved without a supporting RCT.

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