2658 - Rare but Relevant: Exploring Factors behind the Exclusion of Inflammatory Breast Cancer from Breast Cancer Clinical Trials

E. Braschi Jordan¹, Y. Yang², M. C. Stauder³, W. A. Woodward³, R. L. Layman⁴, B. Lim⁴, T. Arnold⁵, A. Lucci⁶, S. X. Sun⁶, S. Saleem⁴, E. B. Ludmir⁷, and C. Kelsey³; ¹Department of Radiation Oncology, University of Florida College of Medicine, Gainesville, FL, ²McWilliams School of Biomedical Informatics, University of Texas Health Science Center at Houston, Houston, TX, ³Department of Breast Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, ⁴Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, ⁵Inflammatory Breast Cancer Network Foundation, Houston, TX, ⁶Department of Breast Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX, ⁷Department of Gastrointestinal Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX

Purpose/Objective(s): Despite being the most aggressive form of breast cancer, inflammatory breast cancer (IBC) has not been a major focus clinical trials, likely due to its rarity. Consequently, IBC treatment guidelines have often been derived from general breast cancer trials, with small, or even absent, numbers of IBC patients. To quantify existing gaps in enrollment of IBC patients in breast cancer trials, we investigated factors associated with IBC patient inclusion by analyzing breast cancer phase III randomized controlled trials (RCTs) and their eligibility criteria. Materials/

Methods: Breast cancer RCTs were identified through ClinicalTrials.Gov. The criteria for participant enrollment, particularly the exclusion of IBC, were gathered from ClinicalTrials.Gov, the study protocol, and the primary publication of endpoint results, as available. Pearson’s Chi-square testing for univariable analyses was used to assess factors associated with IBC patient inclusion. Trial-related factors with p<0.05 on univariable analysis were included in multiple binary logistic regression modeling for multivariable analysis.
Results: We identified 130 RCTs specific to breast cancer with enrollment between 1997-2015. Among these, 44% (57 trials) allowed enrollment of IBC patients, with only 2% (three trials) reporting the number of IBC patients enrolled. The cumulative enrollment across these three trials was 1,391 patients, of which 3.8% (53 patients) had IBC, resulting in an average 3.6% IBC patient inclusion per trial. Trials focusing on patients with metastatic disease showed significantly higher rates of IBC patient inclusion [odds ratio (OR) 13.2, 95% confidence interval (CI): 4.6-44.5, p<0.01]. Similarly, trials with supportive care as the primary intervention were associated with increased IBC patient inclusion (OR 5.9, 95% CI: 1.5-26.0, p=0.014). While trials with chemotherapy as the primary intervention trended toward lower IBC patient inclusion compared to those with alternative interventions, this difference was not statistically significant (p=0.051). Other trial factors, such as industry funding and endocrine therapy, radiotherapy, or surgery as the primary interventions, showed no difference in IBC patient inclusion (p>0.05). There was no significant trend of IBC patient inclusion in trials over time.
Conclusion: IBC patients are inconsistently included and likely poorly represented in phase III trials, leading to less confidence in the efficacy of standard regimens for these patients. Certain trials, such as those examining favorable risk early-stage breast cancers, are not appropriate for IBC inclusion. Conversely, trials investigating more advanced disease should consider allowing IBC enrollment and report IBC patient numbers accrued on public trial registries to allow for global access to their findings.