Griswold, Cassia R.

Introduction: Many patients with prostate cancer have an indication for anticoagulation. This presents a pharmacokinetic dilemma as enzalutamide and apalutamide have significant effects on the metabolism of direct oral anticoagulants. To date, data on coadministration of these agents is limited to pharmacokinetic studies and post-hoc analysis, which suggest no deleterious effects. Our study seeks to elucidate whether the concomitant administration of enzalutamide or apalutamide with apixaban or rivaroxaban results in a clinically meaningful change in thromboembolic events. Methods: We conducted a retrospective, observational cohort study of adult prostate cancer patients on concomitant apalutamide or enzalutamide and apixaban or rivaroxaban for ≥ 3 months from January 1, 2018 to August 9, 2024 at all 3 tertiary sites of our care network. The primary outcome was incidence of deep vein thrombosis, pulmonary embolism, or ischemic stroke. The secondary outcomes included the incidence of switching of anticoagulant therapy or prostate-directed therapy due to concern for drug-drug interaction. The secondary outcomes were assessed in the entire cohort without exclusion. Results: A total of 500 patients were assessed for eligibility, of which 94 were included in the final analysis of primary outcome. The primary outcome occurred in 4 patients (4.3%). The switching of anticoagulant therapy occurred in 32 patients (6.4%). The switching of prostate-directed therapy occurred in 5 patients (1%). Conclusion: This study suggests that there is not an increased incidence of VTE or stroke when compared to historical controls. This study may help clinicians make risk benefit decisions regarding concurrent therapies.

Background: For patients with resected stage III colon cancer, 6 months of adjuvant fluoropyrimidine-based chemotherapy has been the standard of care. The IDEA collaboration aimed to evaluate whether 3 months of adjuvant chemotherapy was noninferior to 6 months. Despite failing to meet its primary endpoint, the subgroup analyses demonstrated noninferiority based on regimen and treatment duration when a risk-stratified approach was used. Patients and Methods: To evaluate the impact of the results of the IDEA collaboration, we evaluated adjuvant chemotherapy prescribing practice patterns, including planned adjuvant treatment regimen and duration from January 1, 2016, to January 31, 2021. The time period was selected to evaluate chemotherapy prescribing patterns prior to the abstract presentation of the IDEA collaboration in June 2017 and after full manuscript publication in March 2018. Results: A total of 399 patients with stage III colon cancer who received adjuvant chemotherapy were included in the analysis. A significant increasing trend for use of 3 months of adjuvant chemotherapy was observed after presentation of the IDEA abstract (P<.001). A significant change in CAPOX (capecitabine/oxaliplatin) prescribing was also observed, increasing from 14% of patients prior to presentation of the IDEA abstract to 48% after presentation (P<.001). Comparing 3 months of CAPOX with 6 months of FOLFOX (fluorouracil/leucovorin/oxaliplatin), 3 months of CAPOX use also steadily increased over time (adjusted odds ratio [aOR], 1.28; 95% CI, 1.20–1.37; P<.001). Among subgroups of interest, no differences in adoption of CAPOX were observed. The adoption of 3 months of CAPOX was similar in patients with low-risk cancer (aOR, 1.27; 95% CI, 1.17–1.37) and those with high-risk cancer (aOR, 1.31; 95% CI, 1.16–1.47). Conclusions: Despite the IDEA collaboration failing to demonstrate noninferiority of 3 months’ duration of adjuvant therapy compared with 6 months, the findings have influenced practice prescribing patterns, favoring CAPOX and a shorter duration of planned adjuvant treatment.

92 Background: Since the publication of the MOSAIC trial, stage III CC has been treated with a six-month (mo) regimen of FOLFOX (fluorouracil, leucovorin, and oxaliplatin) or CAPOX (capecitabine and oxaliplatin). Recently, the IDEA collaboration challenged this practice by demonstrating that the 3-year rate of disease-free survival (DFS) was non-inferior to 6mo of treatment (Rx) when given for low risk CC (83.1 vs. 83.3%) and resulted in significantly lower rates of grade 2 and higher neuropathy. In high risk (T4, N2) patients (pts) the DFS of 3mo of CAPOX was equivocal to 6mo (64.1 vs. 64.0%), while 3mo of FOLFOX was inferior to 6mo (61.5 vs. 64.7%). We hypothesized that trends in prescribing would favor shorter courses of Rx with a preference towards CAPOX given its efficacy across both high and low risk CC. Methods: We performed a retrospective analysis of stage III CC pts from 4 institutions. We evaluated prescribing patterns of 3mo or 6mo of Rx and CAPOX vs. FOLFOX over a period of 5 years from Jan 2016 to Jan 2021, a time period that traverses before and after the release of IDEA. Logistic and multinomial logistic regression models, with a linear time trend, were used to estimate the percentage of pts receiving CAPOX vs. FOLFOX and the combination of Rx and duration, respectively, while adjusting for baseline characteristics. The prescribing patterns in important subgroups were examined by incorporating the interaction term in the models. Results: A total of 366 pts met inclusion criteria. From 2016-2021, there was a significant increase per quarter in patients treated with CAPOX when compared to FOLFOX (OR 1.16 95% CI 1.11 – 1.21, p <.001). Prior to IDEA, 78.3% of pts received 6mo FOLFOX and 7.4% received 3mo CAPOX. Two years after IDEA, only 17.3% of pts were on 6mo FOLFOX compared to 67.5% of pts on 3mo CAPOX (Table). At present, high risk pts are more likely to receive 6mo FOLFOX (47.8%) than 3mo of FOLFOX (3.9%), 3mo CAPOX (25.8%), or 6mo CAPOX (22.4%). Low risk pts are more likely to receive 3mo of CAPOX (67.9%) than other Rx. Conclusions: Our findings suggest that since IDEA, physician practice has significantly changed in favor of CAPOX and shorter courses of Rx. The use of CAPOX has significantly increased overall, presumably due to its efficacy across all risk groups and relatively reduced toxicity.[Table: see text]