Institute of Oncology, Tel Aviv Sourasky Medical Center, Weizmann St 6, Tel Aviv, Israel; Sackler Faculty of Medicine, Tel Aviv University, Chaim Levanon St 30, Tel Aviv, Israel.
Princess Margaret Cancer Centre, University of Toronto, 610 University Ave, Toronto, Canada.
Cancer Treat Rev. 2020 Dec;91:102113. doi: 10.1016/j.ctrv.2020.102113. Epub 2020 Oct 20.
National Comprehensive Cancer Network (NCCN) guidelines can include recommendations for off-label use of anti-cancer drugs. Here, we evaluate NCCN recommendations not supported by US Food and Drug Administration (FDA) approval and explore associations with such recommendations.
All NCCN recommendations for MBC and their supporting data were identified. Drug labels were reviewed to determine whether recommendations are FDA approved. Logistic regression was used to compare FDA approved and off-label recommendations for pre-specified categories, including drug type, tumor subtype, level of recommendation and line of therapy.
Of 124 recommendations identified, 68 (55%) were off-label. Chemotherapy and human epidermal growth factor receptor 2 (HER2) targeted drugs were associated with lower odds of FDA approval (OR = 0.28, p = 0.001 and OR = 0.29, 95% p = 0.005, respectively). Recommendations for endocrine therapy (OR = 3.44, p = 0.009) and non-HER2 targeted treatment (OR = 10.0, p < 0.001) were more commonly FDA approved indications. Compared to combination therapies, monotherapies were more likely to be FDA approved (OR = 3.45, p = 0.001) as were category 1 (OR = 7.63, p = 0.001) and preferred NCCN recommendations (OR = 4.07, p < 0.001). Compared to off-label recommendations, NCCN recommendations of approved drugs were based on significantly higher sample size (mean 477 vs. 342 patients, p = 0.02) and were non-significantly associated with availability of randomized data (OR = 2.0, 95% CI 0.89-4.49, p = 0.09).
More than half of all NCCN recommendations for MBC are off-label, mostly involving chemotherapy containing regimes for HER2 negative disease and combinations which include HER2-targeted drugs. Improved transparency of NCCN guidelines may result from reporting of the strength of the evidence supporting recommendations for MBC.
国家综合癌症网络（NCCN）指南可以包括抗癌药物的标签外使用建议。在这里，我们评估了 NCCN 没有得到美国食品和药物管理局（FDA）批准的建议，并探讨了这些建议与标签外使用之间的关系。
确定了所有用于 MBC 的 NCCN 建议及其支持数据。审查药品标签，以确定建议是否获得 FDA 批准。逻辑回归用于比较预先指定类别的 FDA 批准和标签外建议，包括药物类型、肿瘤亚型、推荐级别和治疗线。
在确定的 124 项建议中，有 68 项（55%）为标签外使用。化疗和人表皮生长因子受体 2（HER2）靶向药物与较低的 FDA 批准可能性相关（OR=0.28，p=0.001 和 OR=0.29，95%p=0.005）。内分泌治疗（OR=3.44，p=0.009）和非 HER2 靶向治疗（OR=10.0，p<0.001）的建议更有可能获得 FDA 批准。与联合治疗相比，单药治疗更有可能获得 FDA 批准（OR=3.45，p=0.001），类别 1（OR=7.63，p=0.001）和首选 NCCN 建议（OR=4.07，p<0.001）也是如此。与标签外建议相比，FDA 批准药物的 NCCN 建议基于明显更大的样本量（平均 477 名 vs. 342 名患者，p=0.02），与随机数据的可用性无显著相关性（OR=2.0，95%CI 0.89-4.49，p=0.09）。
超过一半的 MBC NCCN 建议为标签外使用，主要涉及针对 HER2 阴性疾病的含化疗方案和包含 HER2 靶向药物的联合方案。通过报告支持 MBC 建议的证据强度，NCCN 指南的透明度可能会提高。
