Abstract PS14-13: National comprehensive cancer network (NCCN) recommendations for drugs without US food and drug administration (FDA) approval in metastatic breast cancer: A cross-sectional study

Abstract

Abstract Background: NCCN guidelines include recommendations not approved by the FDA. We aimed to compare the NCCN recommendations for metastatic breast cancer (MBC) with the FDA approved indications and to identify characteristics that are associated with NCCN recommendations for off-label treatment. Methods: All NCCN recommendations for MBC and their supporting data were identified. Drug labels were reviewed to determine whether recommendations are FDA approved indications. Odds ratio (OR) and 95% confidence interval (CI) were calculated to compare between FDA approved and off-label recommendations for pre-specified categories including drug type, tumor subtype, level of recommendation and line of therapy. Results: Of 124 recommendations identified, 68 (55%) were off-label. Chemotherapy and human epidermal growth factor receptor 2 (HER2) targeted drugs were associated with less frequent approved indications (OR=0.28, 95% CI 0.12-0.62, p=0.001 and OR=0.29, 95% CI 0.12-0.70, p=0.005, respectively). Recommendations for endocrine therapy (OR=3.44, 95% CI 1.32-9.09, p=0.009) and non-HER2 targeted treatment (OR=10.0, 95% CI 3.03-33.33, p<0.001) were associated with FDA approved indications. Compared to combination therapies, monotherapies were more likely to be FDA approved (OR=3.45, 95% CI 1.64-7.23, p=0.001). Category 1 (OR=7.63, 95% CI 2.19-26.55, p=0.001) and preferred NCCN recommendations (OR=5.49, 95% CI 2.36-12.77, p<0.001) were more likely to be FDA-approved indications. Compared to off-label recommendations, NCCN recommendations of approved drugs were based on significantly higher sample size (mean 477 vs. 342 patients, p=0.017) and were non- significantly associated with availability of randomized data (OR=1.92, 95% CI 0.87-4.24, p=0.10).Conclusion: 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 targeting drugs. The clarity of the NCCN guidelines can be improved by underlining the strength of the evidence supporting various recommendations for MBC and the hierarchy between various treatment options. Citation Format: Tal Etan, Eitan Amir, Adriana Tibau, Rinat Yerushalmi, Assaf Moore, Daniel Shepshelovich, Hadar Goldvaser. National comprehensive cancer network (NCCN) recommendations for drugs without US food and drug administration (FDA) approval in metastatic breast cancer: A cross-sectional study [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS14-13.