The impact of cancer-related diarrhea on changes in cancer therapy patterns.
Authors: Okhuysen Pablo C. , Schwartzberg Lee S. , Roeland Eric , Anupindi Ruthwik , Hull M , Yeaw Jason , Lee Yi-Chen , Sun Lucille , Franklin Gina , Chaturvedi Pravin , Tam Iris M. 
Published: June 2021

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Background: We studied the impact that cancer related diarrhea (CRD) has on cancer therapy and treatment patterns, including persistence, discontinuation, adherence, and switching of chemotherapy and targeted therapies in patients with and without CRD. Methods: We performed a longitudinal observational study among adult ( > 18 yrs) patients with CRD identified by diagnosis codes or pharmacy claims compared to matched (1:1) non-CRD patients using claims data derived from the IQVIA PharMetrics Plus database. Index date was defined as the date of the first cancer claim, and we re-indexed patients based on CRD claims. Each patient had a 6-month pre-index period and a minimum 3-month follow-up post-index period. To adjust for selection bias and baseline differences, we directly matched the CRD patients to non-CRD patients. Treatment patterns were evaluated and stratified for the first cancer therapy with or without CRD (chemotherapy vs targeted therapy vs both targeted and chemotherapy). Discontinuation was defined as a 30-day gap for chemotherapy and a 14-day gap for targeted therapies from index therapy; switching was a new chemotherapy or targeted therapy prescription within 30 days following discontinuation of index therapy. We computed adherence as the proportion of days covered over the 12-month post-index period and persistence as mean number of days on index therapy. A Cox proportional hazards model was used to estimate the difference in risk of discontinuation of index therapy between CRD and non-CRD cohorts. Results: We evaluated a total of 104,135 matched pairs of CRD and non-CRD adult patients with solid or hematologic cancer; each group further grouped by those receiving either chemotherapy (n = 47,220), targeted therapy (n = 2,427), or both treatments (n = 5,313). Patients with CRD discontinued the index therapy more frequently than non-CRD patients for chemotherapy (81.5% vs 62.3%), targeted therapy (69.2% vs 64.3%) or both (96.0% vs 85.5%) (p < 0.0001). Also, the overall percentage of discontinuation (82.4% vs. 64.6%) was significantly higher among patients with CRD. The mean time to discontinuation (59.6±54.1 vs. 68.3±76.6 days) was significantly lower (p < 0.0001) in patients with CRD. The mean time to switch (72.0±48.6 vs. 96.9±84.0 days), mean persistence (95.1±98.1 vs. 154.3±142.7 days), and mean adherence (25.5%±37.2 vs. 47.9±41%) were significantly lower (all p < 0.0001) among patients with CRD compared to non-CRD. The percentage of patients requiring a dose titration for their index cancer therapy was significantly higher (21.8%) for the CRD cohort versus 8.5% for non-CRD patients (p < 0.0001). Conclusions: Patients with CRD were 40% (adjusted) more likely to discontinue the index therapy than patients without CRD. The persistence of index cancer therapy and time to switch were also lower for patients with CRD. Strategies to control CRD and continue cancer therapy are urgently needed.