Abstract
Abstract Background: Rates of delayed CINV remain high at over 50% following adjuvant chemotherapy for breast cancer, despite the use of multiple antiemetics. Delayed CINV is complex, distressing to patients and it’s incidence is underestimated by physicians. Anti-emetics used with early breast cancer chemotherapy are often directed against acute rather than delayed CINV. Chemotherapy is virtually eliminated from the circulation prior to the delayed phase (24-120 hours post-chemotherapy), suggesting the etiologies for acute and delayed CINV may differ. Chemotherapy and steroids can alter the gastric environment and acid secretion, while chemotherapy can cause gastroesophageal mucositis. We hypothesized that the altered gastric environment, combined with disrupted gastroesophageal mucosa, could contribute to delayed nausea in a proportion of patients. Anecdotal experience suggested proton pump inhibitors, such as Pantoprazole, reduced symptoms in this setting. Methods: This study incorporated a double-blinded crossover design to determine whether Pantoprazole would reduce the incidence of delayed CINV in patients receiving adjuvant, or neoadjuvant breast cancer chemotherapy. Patients were randomized to either pantoprazole or placebo from Day 1-5 after cycle 1, changing to the other intervention for cycle 2. CINV symptoms during the delayed phase were assessed using the Multinational Association of Supportive Care in Cancer (MASCC) Antiemesis Tool and recorded in real time by patients using the PantoCIN ePRO application. With 160 patients, this approach had an 80% power to detect a statistically significant effect (one-sided α (type 1) error of 0.025) of Pantoprazole, if the true effect of Pantoprazole is a 10% reduction in the rates of any delayed CINV compared to placebo. The primary endpoint was the proportion of patients with complete absence of both nausea and vomiting during days 2-5, with severity of CINV and patient preference for intervention described as secondary endpoints. Results: 160 patients were recruited between June 2019 and October 2021, from 10 different cancer centers in New Zealand. Primary statistical analysis has shown a significant reduction in absolute CINV with pantoprazole as the primary end point, with incidence of any CINV symptoms reducing from 61.0% to 49.6% (OR=1.8, 95% confidence interval (1.0 to 3.3); p-value=0.04), in patients with full data. There was also a clear preference for patients to prefer the blinded pantoprazole arm of the 2 cycles of treatment under study, with the proportion of participants who preferred pantoprazole to placebo being 49% and the proportion who preferred placebo to pantoprazole was 25.2%, (difference in proportions 23.8% and 95% confidence interval 12.4 to 35.2; p=0.0017). Conclusion: CINV is a common and distressing complication of early breast cancer chemotherapy, which persists despite the use of a range of current antiemetics. Pantoprazole is a cheap, well-tolerated agent without significant drug interactions, which clearly ameliorates this symptom in a significant proportion of patients and should be considered as a standard prophylactic intervention. Citation Format: Navin Wewala, Katrina Sharples, Yujin Kim, Sarah Benge, Robert Cartwright, Louise Clement, Ying Huang, Richard Isaacs. PantoCIN: Pantoprazole’s effectiveness as prophylaxis against delayed Chemotherapy-Induced Nausea and Vomiting (CINV) in patients receiving adjuvant or neoadjuvant breast cancer chemotherapy [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 PD8-01.