Abstract OT3-30-01: A randomized double-blind placebo controlled phase 3 trial on the effect of Salovum™ and SPC-Flakes™ on abemaciclib-induced gastrointestinal toxicity in early breast cancer – the ASF-BC study
Authors: Lindman Henrik , Nygren Peter , Valachis Antonis 
Published: March 2023

Abstract
Background: In patients with high-risk luminal breast cancer, the addition of CDK 4/6-inhibitor abemaciclib to adjuvant endocrine therapy for two years has been associated with improved disease-free survival and is now recommended as the preferred treatment strategy for this patient group. However, patients treated with abemaciclib frequently (82%) experience diarrhea which primarily occurs during the first three months from treatment initiation and seems to impact patients’ quality of life. No proactive strategy to reduce the occurrence of abemaciclib-induced diarrhea is proposed but patients are recommended to start with loperamide upon the occurrence of diarrhea to be combined with treatment interruption and dose adjustment as needed. Cholera induced diarrhea, as well as other forms of diarrhea-inducing agents, has been shown to elicit a stimulated, endogenous production of a protein, named ”antisecretory factor”, ASF, which acts by modulating secretion of water and ions but also counteracts inflammatory processes. ASF is commercialized as Salovum® and registered by the EU authorities as ”Food for specific medical purposes”. Another way to increase ASF and, thus, to achieve benefit, is to induce its production/conversion by ingestion of malted oat flakes (SPC-flakes®) which has been recommended or considered for several secretory pathological conditions. Salovum has been shown to rapidly, ie within hours to a few days, antagonize diarrheal diseases of various etiologies. It has also been used against high fluid passages and inflammation in Crohn disease, Colitis ulcerosa and carcinoids in adults. SPC-flakes have similar effects but need weeks of administration to emerge. Importantly, to raise body ASF, by Salovum or SPC-flakes, for the above indications has not been associated with adverse effects. Methods: This is a randomized double-blind multicenter phase III study aiming to investigate a proactive strategy including Salovum and SPC-flakes to prevent the occurrence of abemaciclib-induced diarrhea in patients with early breast cancer treated with abemaciclib. A total of 100 patients will be randomized, in a 1:1 manner, between 13 weeks with Salovum/SPC flakes (A) or placebo (B). The study will be conducted in up to ten different oncology departments in Sweden starting in Q3 2022. Primary objective: Occurrence of any-grade (mild, moderate, severe) diarrhea according to the Systemic Treatment-Induced Diarrhea Assessment Tool (STIDAT; patient-reported outcome). Secondary objectives: Occurrence of any-grade diarrhea according to CTCAE v. 5.0, health-related quality of life (QoL), other adverse events related to abemaciclib, adherence to planned abemaciclib treatment, adherence to and pharmacodynamic effect from study products, safety of investigational products, sick leave duration, breast cancer recurrence. Investigational product, dosage and mode of administration: Salovum/placebo egg powder high in antisecretory factor, 4 g. Four sachets, ie 16 g q 8 h for 5 - 7 days before start of abemaciclib. The appropriate amount of Salovum is mixed with 100 – 200 ml of suitable liquid, e.g., fruit juice, and ingested orally. SPC-flakes/placebo flat dose of 75 g/d divided in 2 – 4 doses started in parallel with Salovum/placebo to be continued during the first 12 weeks of treatment with abemaciclib. End of study: All included patients will be followed using questionnaires up to 12 weeks from initiation of abemaciclib. After 12 weeks, all the patients will be followed through electronic medical records until the end of abemaciclib treatment (up to two years) for collecting potential adverse events and information on sick leave. Data from electronical medical records regarding recurrence and subsequent therapy will be collected until breast cancer recurrence or up to 5 years from initiation of abemaciclib.
Citation Format: Henrik Lindman, Peter Nygren, Antonis Valachis. A randomized double-blind placebo controlled phase 3 trial on the effect of Salovum™ and SPC-Flakes™ on abemaciclib-induced gastrointestinal toxicity in early breast cancer – the ASF-BC study [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr OT3-30-01.