An internal review of chemotherapy toxicities in patients with pancreatic cancer.

e16258 Background: Cytotoxic chemotherapy remains the standard of care in the treatment of pancreatic ductal adenocarcinoma (PDAC). There is more excitement in the last few years regarding the use of neoadjuvant chemotherapy even when the disease is resectable. In this analysis, we sought to study the different regimens used in our institutions, in regards to setting and toxicity. Methods: We retrospectively reviewed all patients diagnosed with pancreatic adenocarcinoma at Allegheny General Hospital between 2009-2020. Data was extracted from electronic medical records and de-identified. Institutional Review Board approval was obtained. Descriptive analysis was undertaken and multivariate analysis was performed to compare differences in the prevalence of toxicity across the regimens and demographics using Stata version 16. The primary outcome was the rate of toxicity that prompted dose adjustment, stratified by the setting chemotherapy was administered (neoadjuvant, adjuvant, or palliative). Results: Of the 121 patients studied, 88 patients received chemotherapy. Median age was 69 years. 66 patients (55%) were females. 40 patients suffered from adverse effects requiring a dose adjustment. 85% of the adverse effects occurred in Caucasians. 15 out of 37 patients (42.9%) who received Folfirinox, 15 out of 31 patients (48.4%) who received gemcitabine and nab-paclitaxel, 6 out of 10 patients (60.0%) who received gemcitabine and capecitabine, 3 out of 4 patients (75.0%) who received gemcitabine monotherapy required dose adjustment (table). Folfirinox and gemcitabine with nab-paclitaxel were statistically compared and found to be not significant (p-value=0.12). No significant impacts of race, gender, or age were noted in a multivariate model. Conclusions: Approximately 42% of patients receiving chemotherapy suffered from toxicities that required dose adjustments. We found a trend toward more use of neoadjuvant chemotherapy in resectable PDAC with a similar toxicity rate compared with other settings.[Table: see text]

P508 Dose adjustment in patients with moderate to severe ulcerative colitis: results from year 3 of the UNIFI maintenance study long-term extension

Background The UNIFI randomized-withdrawal maintenance study and long-term extension (LTE) evaluated the safety and efficacy of subcutaneous (SC) ustekinumab (UST) in patients with moderately to severely active ulcerative colitis (UC) who had responded to intravenous (IV) UST during induction. We evaluated the efficacy of UST dose adjustment through Week (Wk) 152 of the long-term extension (LTE). Methods 523 intravenous UST induction responders were randomized to SC maintenance therapy (SC placebo [PBO], n=175; UST 90mg every 12 weeks [q12w], n=172; or UST 90mg q8w, n=176). 284 UST patients who completed wk44 entered the LTE. PBO patients were discontinued after wk44 unblinding. Based on the investigator’s clinical judgement of their UC disease activity, patients in the LTE were eligible to receive dose adjustment starting at Wk 56: PBO to q8w, q12w to q8w, and q8w to q8w (sham adjustment). Patients in PBO or q8w groups were only eligible for dose adjustment or sham dose adjustment before unblinding. Patients were assessed for symptomatic remission, partial Mayo scores, and inflammatory markers ≥16 wks after dose adjustment. Results Overall, 60 patients (42.6%) in the q12w group and 40 patients (28.0%) in the q8w group underwent dose adjustment (or sham dose adjustment) prior to Wk 156 of the LTE; 51 and 39 patients in each group, respectively, had dose adjustment at Wk 136 or before, providing≥16 wks of data after dose adjustment (Table). At the first visit ≥16 weeks after dose adjustment, 70.6% of patients who adjusted from q12w to q8w and 61.5% who sham dose adjusted from q8w to q8w were in symptomatic remission. At the time of dose adjustment, 27/51 patients (52.9%) in the q12w group and 25/39 patients (64.1%) in the q8w group were in symptomatic remission. Of those who were in symptomatic remission at the time of dose adjustment, the majority (81.5% and 68.0%, respectively) were maintained in symptomatic remission at the first visit ≥16 wks after dose adjustment. Of those who were not in symptomatic remission at the time of dose adjustment, 58.3% and 50.0%, respectively, were in symptomatic remission at the first visit ≥16 wks after dose adjustment. Mean partial Mayo scores and CRP levels decreased after dose adjustment (Table). Conclusion Patients may benefit from UST dose adjustment to q8w.

Abstract 15380: Association of Change in Body Mass Index With Premature Atrial Contractions Frequency and Atrial Fibrillation in Older Age: The Atherosclerosis Risk in Communities (ARIC) Study

Introduction: The proportions of obese and aging adults are rapidly growing. While obesity and advancing age are associated with atrial fibrillation (AF), data are limited on weight change in the elderly as a risk factor for premature atrial contractions (PACs)—which are known to precede AF—or AF. Hypothesis: Compared to a stable body mass index (BMI) over time, increasing BMI will be associated with a higher PAC frequency and AF in elderly participants in ARIC. Methods: We included N=2,070 ARIC participants [age mean ± SD 79 ± 4.5 years, 59% female] without known AF who attended visit 6 and wore an ambulatory ECG-monitoring device (Zio XT® Patch, iRhythm Technologies Inc.) for ≥48 hours. BMI change was defined as change between V5 (2011-13) and V6 (2016-17) and was categorized into 4 groups: >10% decrease, 2 to 10% decrease, -2 to 2% change (stable BMI) and > 2% increase. PAC frequency was defined as percent of beats that are PACs. Linear regression was used to evaluate the association between BMI change and % PAC. Incident AF was ascertained after V6 through 2018 from hospital discharge codes and death certificates. Logistic regression was used to evaluate the association between BMI change and incident AF. Results: Median PACs per hour were 8.84. Participants with >2% BMI increase had 0.35% (95% CI: 0.06%-0.64%) higher frequency of PACs compared to those with stable BMI after multivariable adjustment (Table). After a mean (SD) follow-up of 19 (7) months, there were 82 incident AF cases. Compared to stable BMI, both >2% BMI increase and 2 to 10% decrease were nonsignificantly associated with higher odds of AF compared with stable BMI after multivariable adjustment (Table). Conclusion: Increasing BMI in the elderly is associated with higher PAC frequency and is nonsignificantly associated with higher odds of AF compared to stable BMI. This finding suggests that weight management, which is currently emphasized in middle age, may also apply in late-life to prevent atrial arrhythmias.

P448 Dose adjustment in patients with moderate-to-severe ulcerative colitis: results from the UNIFI maintenance study long-term extension

Background The UNIFI randomised-withdrawal maintenance study evaluated the safety and efficacy of subcutaneous (SC) ustekinumab (UST) in patients (patients) with moderately to severely active ulcerative colitis (UC) who had responded to intravenous (IV) UST during induction. We evaluated the efficacy of UST dose adjustment during the long-term extension (LTE). Methods At Week (Week) 0 of the 44 weeks maintenance study, 523 patients who had responded to IV UST induction were randomly assigned in a 1:1:1 ratio to placebo (PBO) SC, UST SC 90 mg q12w, or 90 mg q8w. Patients who completed the maintenance study were eligible to enter the LTE if the investigator thought they would benefit from continued treatment. PBO patients were discontinued from the LTE after the maintenance study was unblinded and the analysis was complete. Based on investigator’s clinical judgement of UC disease activity, patients in the LTE were eligible to receive dose adjustment starting at Week 56: PBO to q8w, q12w to q8w, and q8w to q8w (sham adjustment). PBO patients were only eligible for dose adjustment before unblinding. Patients were assessed for symptomatic remission (SR), partial Mayo scores, and inflammatory markers ≥16 weeks after dose adjustment. Results Symptomatic remission was maintained through Week 92 among patients treated with UST regardless of dose adjustment in the LTE (Figure). Overall, 40 (28.4%) and 37 (25.9%) patients in the q12w and q8w groups, respectively, underwent dose adjustment (or sham dose adjustment) prior to Week 92 of the LTE. Among patients who received dose adjustment at Week 76 or before and had data ≥16 weeks after dose adjustment, symptomatic remission was observed in 70.0% in the q12w-to-q8w group and 71.4% in the q8w-to-q8w group, the majority of whom were in symptomatic remission at the time of the dose adjustment (Table). The safety profile of UST in patients who received dose adjustment was generally consistent with the overall safety profile of UST. Conclusion Patients may benefit from UST dose adjustment to q8w. However, the majority of UST-treated patients were in SR at the time of dose adjustment in this study. No new safety signals were observed among patients who dose adjusted.

An internally consistent data product for the world ocean: the Global Ocean Data Analysis Project, version 2 (GLODAPv2)

For version 2 of the Global Ocean Data Analysis Project (GLODAPv2) we collated data from 724 scientific cruises covering the global ocean: data assembled in the previous efforts GLODAPv1.1 (Global Ocean Data Analysis Project version 1.1) in 2004, CARINA (CARbon IN the Atlantic) in 2009/10, and PACIFICA (PACIFic ocean Interior CArbon) in 2013, and an additional 168 cruises. Twelve core parameters (salinity, oxygen, macronutrients, seawater CO2 chemistry parameters and halogenated transient tracers) have been subjected to extensive quality control including systematic evaluation of biases between cruises. The data are available in two formats: (i) as submitted but updated to WOCE exchange format whenever required, and (ii) as a merged and calibrated data product. In the latter, adjustments have been applied to remove significant biases, respecting occurrences of any known or likely time trends. Adjustments determined by previous efforts have been re-evaluated. Hence, GLODAPv2 is not a simple merge of previous collections and some new data, but represents a unique, internally consistent data product. The original data and their documentation and doi codes are available at the Carbon Dioxide Information Analysis Center (http://cdiac.ornl.gov/oceans/GLODAPv2/). This site also provides access to the calibrated data product, which is provided as a single global file or 4 regional ones: the Arctic, Atlantic, Indian, and Pacific Oceans, under the doi:10.3334/CDIAC/OTG.NDP093_GLODAPv2. The product files also include significant ancillary and approximated data. The latter were obtained either by interpolation of, or by calculation from, measured data. This paper documents the GLODAPv2 history, methods, and products, including a broad overview of the secondary quality control results. The magnitude of and reasoning behind the adjustments are available on a per cruise and parameter basis in an online Adjustment Table.

Adjusting for treatment crossover in the METRIC metastatic melanoma (MM) trial for trametinib: Preliminary analysis.

9040 Background: In METRIC, a randomized phase III study, trametinib significantly improved PFS (hazard ratio [HR]=0.44 [95% CI 0.31–0.64; p<0.001]) vs chemotherapy (chemo) in patients (pts) with BRAF V600E+ MM and no brain metastases. Median overall survival (OS), a secondary endpoint, has not yet been reached. OS results are likely to underestimate the effect of trametinib as pts progressing on chemo could cross over to experimental treatment (trt). This analysis attempts to adjust for confounding effects of trt crossover on OS in the overall population and first line (1L) subgroup using current METRIC results. Methods: Randomization-based crossover adjustment methods – Rank Preserving Structural Failure Time Models (RPSFTM) and the Iterative Parameter Estimation (IPE) algorithm – were used. We conducted two sets of analyses testing different assumptions regarding the durability of the trt effect. “Trt group” analyses adjusted for crossover under the assumption that the trt effect is maintained until death regardless of trt duration; “On trt – observed” analyses adjusted for crossover under the assumption that the trt effect disappears upon trt discontinuation. Results are presented as HRs. Results: 178 and 95 MM pts were randomized to trametinib and chemo, respectively; 49.5% of chemo pts crossed over to trametinib as of data cut off (Oct. 2011). Median follow-up was 4.9 months and 19.8% deaths occurred across both arms. Crossover adjustment results are presented in the Table. Conclusions: RPSFTM and IPE “trt group” analyses resulted in OS HR point estimates that represented greater trt effects in the overall population and 1L subgroup compared to the unadjusted HRs. Results are exploratory because few deaths have been observed in the current dataset. Future analyses on a mature dataset should produce more robust estimates of the OS trt effect after crossover adjustment. [Table: see text]