BRE12-158: A Postneoadjuvant, Randomized Phase II Trial of Personalized Therapy Versus Treatment of Physician's Choice for Patients With Residual Triple-Negative Breast Cancer

PURPOSE Patients with triple-negative breast cancer (TNBC) with residual disease after neoadjuvant chemotherapy (NAC) have high risk of recurrence with prior data suggesting improved outcomes with capecitabine. Targeted agents have demonstrated activity across multiple cancer types. BRE12-158 was a phase II, multicenter trial that randomly allocated patients with TNBC with residual disease after NAC to genomically directed therapy versus treatment of physician choice (TPC). PATIENTS AND METHODS From March 2014 to December 2018, 193 patients were enrolled. Residual tumors were sequenced using a next-generation sequencing test. A molecular tumor board adjudicated all results. Patients were randomly allocated to four cycles of genomically directed therapy (arm A) versus TPC (arm B). Patients without a target were assigned to arm B. Primary end point was 2-year disease-free survival (DFS) among randomly assigned patients. Secondary/exploratory end points included distant disease-free survival, overall survival, toxicity assessment, time-based evolution of therapy, and drug-specific outcomes. RESULTS One hundred ninety-three patients were randomly allocated or were assigned to arm B. The estimated 2-year DFS for the randomized population only was 56.6% (95% CI, 0.45 to 0.70) for arm A versus 62.4% (95% CI, 0.52 to 0.75) for arm B. No difference was seen in DFS, distant disease-free survival, or overall survival for the entire or randomized populations. There was increased uptake of capecitabine for TPC over time. Patients randomly allocated later had less distant recurrences. Circulating tumor DNA status remained a significant predictor of outcome with some patients demonstrating clearance with postneoadjuvant therapy. CONCLUSION Genomically directed therapy was not superior to TPC for patients with residual TNBC after NAC. Capecitabine should remain the standard of care; however, the activity of other agents in this setting provides rationale for testing optimal combinations to improve outcomes. Circulating tumor DNA should be considered a standard covariate for trials in this setting.

TAMI-48. THE KETOGENIC DIET IS INEFFECTIVE IN PRECLINICAL MODELS OF IDH1 WILD-TYPE AND IDH1 MUTANT GLIOMA

Despite decades of intensive research, infiltrative gliomas are still usually lethal and challenging to treat. A subset of gliomas contains mutations in isocitrate dehydrogenase 1 (IDH1mut), which disrupts cellular biochemistry; such gliomas are generally less aggressive than their IDH1 wild-type (IDH1wt) counterparts. Some preclinical studies have suggested that a ketogenic diet (KD), characterized by low-carbohydrate and high-fat content, may be beneficial against a variety of cancers, including gliomas. However, not all studies have shown promising results, and to date, no study has addressed the sensitivity of glioma cells to KD in the specific context of the endogenous IDH1mut metabolic landscape. The aim of the current study was to compare the effects of KD in preclinical models to IDH1wt versus IDH1mut gliomas. In vitro treatment of patient-derived IDH1wt and IDH1mut glioma cells with the ketone body β-hydroxybutyrate showed no significant effect on cell proliferation in a low glucose culture environment. Likewise, the in vivo flank growth rates of these patient-derived IDH1wt and IDH1mut glioma xenografts showed no significant difference when mice were fed KD versus regular diet (GBM12 p=0.98, GBM164 p=0.4, GBM196 p=0.11). Finally, KD had no effect on the survival of mice engrafted with isogenic Sleeping-Beauty transposase-engineered IDH1wt (median control survival 22 days versus treatment 23 days, p=0.23) or IDH1mut glioma cells (median control survival 26.5 days versus treatment 26 days, p=0.81). These data suggest that IDH1mut gliomas are not more responsive than IDH1wt gliomas to KD, and that clinical trials further exploring KD in this subset of glioma patients are probably not warranted.

Use and Safety of Prophylactic Endoscopy From a Single Center Serving Urban and Rural Children With Portal Hypertension

Background: Prophylactic endoscopy is routine in adults with portal hypertension (PHTN), but there is limited data in pediatrics. We sought to describe our experience with prophylactic endoscopy in pediatric PHTNMethods: Retrospective cohort study of 87 children who began surveillance endoscopy prior to gastrointestinal bleeding (primary prophylaxis) and 52 who began after an episode of bleeding (secondary prophylaxis) from 01/01/1994 – 07/01/2019. Results: Patients who underwent primary prophylaxis had a lower mean number of endoscopies (3.897 vs 6.269, p = 0.001). The primary prophylaxis group was less likely to require a portosystemic shunt (6% vs 15%, p < 0.001) with no difference in immediate complications (1% vs 2%, p = 0.173), 2-week complications (1% vs 2%, p = 0.097), need for transplant (24% vs 27%, p = 0.0819) or death (5% vs 13%, p = 0.061). No deaths were related to variceal bleeding or endoscopy. Conclusions: Primary and secondary endoscopic prophylaxis should be considered safe for the prevention of variceal hemorrhage in pediatric portal hypertension. There are differences in outcomes in primary and secondary prophylaxis, but unclear if this is due to patient characteristics versus treatment strategy. Further study is needed to compare safety and efficacy to watchful waiting.

Effects of Treatment Adherence on Quality of Life in Hypoparathyroid Patients

Objectives This study aimed to evaluate the current situation of hypoparathyroid patients and to investigate the relationship between treatment adherence and quality of life. Study design Prospective, multicentre study. Methods Adult patients presenting with the diagnosis of hypoparathyroidism to 20 different endocrinology clinics were included. They were receiving conventional therapies for hypoparathyroidism, using calcium, active vitamin D, and magnesium. We collected data on demographic features, disease- and treatment-related information, and results of routine laboratory tests, treatment adherence, and presence of complications. Beck Depression Inventory, Beck Anxiety Inventory, and Short Form-36 quality of life assessments were administered. Results Among the 300 patients studied, 60.7% were adherent to their treatment, and 34.1% had complications. Anxiety and depression scores were significantly higher in non-adherent versus treatment-adherent patients (p<0.001 and p=0.001, respectively). Most of the domains of quality-of-life scores were also significantly lower in non-adherent patients. Both anxiety and depression scores showed significant, negative correlations with serum calcium and magnesium concentrations (r=−0.336, p<0.001 and r=−0.258, p<0.001, respectively). Conclusions Nearly 40% of the patients were non-adherent to conventional treatment for hypoparathyroidism, and such patients had higher anxiety and depression scores and poorer quality of life scores. Conventional treatment might not be sufficient to meet the needs of patients with hypoparathyroidism. In addition to seeking new therapeutic options, factors influencing quality of life should also be investigated and strategies to improve treatment adherence should be developed.