Pancreatic-enzyme replacement therapy with pancrelipase plus chemotherapy for patients with pancreatic adenocarcinoma with cachexia and exocrine pancreatic insufficiency (PANCAX-3).

e24059 Background: Pancreatic-enzyme replacement therapy (PERT) is the standard of care to prevent maldigestion, malnutrition, and excessive weight loss in patients with exocrine pancreatic insufficiency (EPI). The utility of this therapy for patients with EPI in the setting of pancreatic ductal adenocarcinoma (PDAC) is unclear. We report results of a single site phase 2 trial for PERT with Pancreaze® plus standard of care (SOC) chemotherapy in PDAC patients with cachexia and EPI. The primary outcome measure was to assess feasibility of completing PERT during the first 8 weeks of treatment. Secondary outcome measures included weight stability, mean change in stool frequency, stool consistency from Cycle 1 (C1) to Cycle 3 (C3) (after 8 weeks of PERT), mean change in serum levels of fat soluble vitamins (A, D, E, K) from baseline to end of study, functional activity, and safety. Methods: Feasibility was defined as adherence to therapy of ≥50% of the needed total lipase units in the first 8 weeks of treatment (84,000 IU lipase units per meal, 42,000 IU lipase units per snack). Data are presented as frequencies (%) for categorical variables and means ± standard deviation for continuous variables. Weight stability, stool frequency, fat soluble vitamin levels, walk speed, and hand grip strength compared using two-sample paired t-tests. Stool consistency (Bristol stool type) compared using Fisher’s exact test. Results: Of 36 patients enrolled, 30 were evaluable for primary endpoint. Median age was 70. 73.3% (22/30) were female. 33.3% (10/30) were borderline resectable, 33.3% (10/30) locally advanced, and 33.3% (10/30) advanced/metastatic. 30 patients completed 8 weeks of PERT and 96.7% (29/30) were compliant. Efficacy results include PR (6.7%, 2/30), SD (66.7%, 20/30) and PD (23.3%, 7/30). Imaging not available for 1 patient. 6 patients experienced grade 1/2 GI toxicities (nausea, bloating, diarrhea, abdominal pain) deemed possibly/probably related to PERT. Grade 3/4 AEs included fatigue, infection, and hematologic toxicities deemed unrelated to PERT. Among evaluable patients, weight remained stable (-0.01±0.07 kg/BMI, p = 0.511) and there was a trend toward reduced stool frequency (p = 0.052) from C1 to C3. Stool consistency from C1 to C3 showed significant association (p = 0.035). Serum fat soluble vitamins, functional activity by walk speed and hand grip strength were also explored and no statistically significant differences were observed from C1 to C3 among the evaluable patients. Conclusions: PERT plus SOC chemotherapy for PDAC patients with cachexia and EPI is feasible and well-tolerated. Patients taking PERT experienced weight stability. PERT may aid in reducing stool frequency and further analysis is warranted into how PERT affects stool consistency. Clinical trial information: NCT04098237 .