Background. Malnutrition and physical inactivity are common in patients with advanced cancer and are associated with poor outcomes. There are increasing data that altered body composition is related to the pharmacokinetic properties of cancer therapies. These adverse conditions may impact outcomes in early-phase oncology clinical trials. Materials and Methods. We aimed to understand the relationships between baseline nutrition and exercise status with important trial endpoints including treatment-related toxicity and survival. Baseline assessments of nutrition and exercise status were conducted in patients prior to initiation of phase I and II oncology clinical trials. Patients were followed prospectively for the onset of adverse events. Tumor response and survival data were also obtained. Fisher's exact test and chi-square analysis were used to determine statistical significance. Kaplan-Meier curves were used to compare patient duration on study and survival.Results. One hundred patients were recruited, of whom 87 were initiating a phase I trial. Sixty percent were initiating trials studying immunotherapeutic agents. Critical malnutrition was found in 39% of patients, and 52% were sedentary. Patients who were malnourished had significantly increased rates of grade ≥ 3 toxicity (p = .001), hospitalizations (p = .001), and inferior disease control rate (p = .019). Six-month overall survival was significantly reduced in malnourished patients versus nonmalnourished patients (47% vs. 84%; p = .0003), as was median duration on study (48 days vs. 105 days; p = .047). Being sedentary at baseline was associated with decreased duration on study (57 days vs. 105 days; p = .019). Conclusion. Malnutrition and sedentary lifestyle are highly prevalent in patients enrolling on early-phase oncology clinical trials and are associated with poor outcomes. The quality of data from these studies may be compromised as a result of these pre-existing conditions. The Oncologist 2020;25:161-169 Implications for Practice: Phase I and II trials are critical steps in the development of effective cancer therapeutics, yet only a small percentage of agents are ultimately approved for human cancer care. Despite increasing awareness of the interactions between malnutrition, sarcopenia, and treatment-related outcomes such as toxicity and response, these factors are not commonly incorporated into therapeutic decision making at the time of clinical trial consideration. Nutritional status and physical performance may be key biomarkers of mechanisms mediating treatment-related toxicity, dose modifications, risk of hospitalizations, and success of novel agents. This study advocates that a baseline nutritional assessment and early nutritional support may improve tolerability and response to experimental therapies.

Purpose Psychological distress is common in patients with cancer and is associated with lower quality-of-life (QOL). Although distress among oncology outpatients undergoing standard therapy has been widely studied, few studies have evaluated distress among patients enrolling on Phase I therapeutic clinical trials. Thus, we aimed to characterize levels of distress and types of stressors in patients enrolling on Phase I clinical trials. Methods Participants completed the National Comprehensive Cancer Network Distress Thermometer (NCCN DT) and Problem list and measures of anxiety and depression at the time of Phase I clinical trial initiation. Results We enrolled 87 patients (95% with metastatic/incurable disease) who were initiating a Phase I clinical trial. Analyses revealed a high prevalence of distress (51%) and anxiety (28%). There were significant correlations between overall distress and practical problems ( r = 0.31, p = 0.016), family problems ( r = 0.35, p = 0.006), and emotional problems ( r = 0.64, p < 0.001), but not physical problems ( r = 0.17, p = 0.206). Conclusions Patients may be better prepared to manage physical stressors but not practical, emotional, or family stressors at the time of Phase I trial enrollment. Implications for Cancer Survivors Phase I trial patients experience high levels of distress which may be due to the rigors of previous therapies therapy and related emotional and social stressors related to the poor prognosis of their advanced cancer diagnosis. Distress may go unidentified without screening which is not standard practice at the time of Phase I trial consideration. Future studies should evaluate strategies to routinely identify and intervene upon addressable stressors in patients participating in Phase I clinical trials.

770 Background: Patients (pts) with cancer, in particular GI malignancies, are vulnerable to CMN from both tumor-related digestive symptoms and treatment-related toxicity (TRT). CMN is associated with poor cancer outcomes, including reduced quality of life, poor treatment tolerance and decreased survival. P1/2 trial participants are not routinely screened for CMN or potentially associated psychological and physical activity impairments. Methods: Baseline assessments of nutrition (PG-SGA), distress (NCCN-DT), anxiety (HADS-A), depression (HADS-D), and sedentary lifestyle (SL, Godin-LTQ) were conducted in pts beginning a P1/2 trial. CMN was defined as a PG-SGA score of ≥9. Statistical significance was determined by Fisher’s exact test. A regression model was used to identify a composite predictor of CMN. Results: 100 pts (87% P1, 13% P2) were enrolled. Results of assessments are shown in Table 1. 39% of pts had CMN and 52% had a SL. CMN was more common in non-whites (p = 0.05) and those on P1 trials (p = 0.073). No differences were noted by age, gender, or prior lines of therapy. CMN was strongly associated with depression (p < 0.001) and SL (p < 0.001). 31 pts had GI malignancies [CRC (15), pancreas (8), and other (8)]. CMN was more prevalent in GI pts than non-GI (61% vs 29%, p = 0.004). When evaluating the predictive value of commonly used clinical indicators for CMN such as BMI ( < 25), weight loss (WL) past 2 weeks, or WL past month, having 2/3 of these indicators was the optimal cut-point predictor of CMN (76% sensitivity, 85% specificity). TRT data collection is ongoing. Conclusions: CMN and SL are highly prevalent in P1/2 trial pts, particularly in those with GI cancers and minorities. CMN is strongly associated with depression and SL. A composite clinical indicator (BMI + WL) may be most useful in screening for CMN. Urgent nutritional interventions in these participants may be warranted in light of magnified mortality and toxicity risks. [Table: see text]

e18648 Background: Cancer-related malnutrition and cachexia can lead to body composition changes. BCM can be assessed at the third lumbar (L3) vertebra by CT, which is available as part of pre-trial evaluation. We previously found that malnutrition and low psoas muscle area (PMA) are associated with adverse P1 outcomes including higher rates of ≥ Grade 3 toxicity (G3T). Here we evaluate the relationships between comprehensive cross-sectional muscle and adipose tissue BCM at L3 on P1 outcomes. Methods: Baseline CT scans for 82 patients (pts) were reviewed and images at the level of L3 were identified by 3 independent reviewers. A CT L3 image selected by at least 2 reviewers underwent analysis by Slice-O-Matic software (Tomovision, Canada) to generate BCM including: skeletal muscle area (SMA), skeletal muscle radiodensity (SMD), and adipose tissue area [intermuscular (IMAT), visceral (VAT), subcutaneous (SAT), and total adipose (TAT)] in cm2. SMA was normalized by height (m2), yielding cross-sectional skeletal muscle index (SMI). We stratified pts by having a SMI, SMD, IMAT, VAT, SAT, and TAT above or below the median value. We evaluated for associations between BCM and the following outcomes: rates of ≥ G3T, frequency of dose reductions/interruptions, hospitalizations, tumor response, disease control, duration on study (DOS), and overall survival (OS). Chi-square analysis was used to determine statistical significance between groups. Kaplan-Meier curves were used to compare DOS and OS. A multivariable analysis (MVA) was conducted via logistic regression to evaluate the association between SMI, VAT, PMA and ≥ G3T controlling for age and gender. Results: 82 P1 pts were included (38 M, 45 F), with a median age of 60 (range 28-85). The most common disease site was gastrointestinal (33%). Mean SMI was 44.78 cm2/m2 (range 25.70-79.89). Higher SMI was associated with a reduced risk of ≥ G3T (36.6% vs 58.5%; p = 0.047) and a trend towards improved OS (p = 0.07). There was no association between SMD, IMAT, SAT, or TAT and toxicity, however, higher VAT was associated with reduced risk of ≥ G3T (31.7% vs 63.4%, p = 0.004), and improved response to therapy (p = 0.001). A MVA controlling for age and gender showed that reduced SMI (AUC 0.7072), increased VAT (AUC 0.7597), and reduced PMA (AUC 0.757) were similar in their ability to predict ≥ G3T. Conclusions: P1 trials are designed to determine the safety and tolerability of investigational agents. In this population of P1 pts, BCM including higher baseline CT L3 SMI and VAT were associated with a reduced risk of ≥ G3T. BCM were also tied to efficacy as high VAT was associated with improved tumor response while a trend towards improved OS was noted for pts with higher baseline SMI. Future research should examine the value of integrating CT-based BCM into dose-selection algorithms when evaluating safety in P1 trials to minimize treatment-related toxicity and optimize therapeutic benefit.

7007 Background: Malnutrition and cancer cachexia can lead to loss of muscle mass (sarcopenia) and are associated with poor outcomes. Muscle status can be evaluated by computed tomography (CT)-based radiographic measures, specifically at the L3 vertebrae where the psoas and other core muscles reside. We previously found that baseline malnutrition was associated with worse phase 1 clinical trial outcomes including increased toxicity and reduced survival (Jain et al. Oncologist, 2019). We sought to evaluate the relationship between muscle status and phase 1 trial outcomes. Methods: CT-based psoas muscle area (PMA) and psoas muscle density (PMD) were evaluated in 83 patients who enrolled in a phase 1 trial. We localized the L3 vertebral body on axial imaging and manually outlined the psoas muscle to calculate PMA (standardized to height) and PMD. Two reviewers independently conducted the analyses. We stratified patients by having a PMA or PMD above or below the group’s median. We evaluated for associations between PMA/PMD and the following clinical trial outcomes: rates of grade ≥ 3 toxicity, frequency of dose reductions/interruptions, hospitalizations, tumor response, duration on study (DOS), and overall survival (OS). We also evaluated for correlations between PMA/PMD and a validated measure of nutritional status, the PG-SGA. Chi-square analysis was used to determine statistical significance between groups. Kaplan-Meier curves were used to compare DOS and OS. Results: 83 patients were included (38 male, 45 female), with a median age of 60 (range 28-85). The most common cancer type was gastrointestinal (33%). Mean PMA was 2.89 cm2/m2 (range 1.41-5.72) and mean PMD 37.77 Hounsfield units (range 13.27-56.18). PMA above the median was associated with a reduced risk of grade ≥ 3 toxicity (32.5% vs 67.4%, p = 0.001). There was no association between PMD and grade ≥ 3 toxicity, or between PMA/PMD and other phase 1 trial outcomes. There was a significant correlation between nutritional status and PMA (r = -0.278, p = 0.01) but not PMD. Conclusions: PMA and PMD are readily available CT-based measures of muscle status. In oncology phase 1 clinical trial participants, lower baseline PMA was associated with a two-fold increased risk of grade ≥ 3 toxicity. Baseline PMA was moderately correlated with nutritional status which was previously shown to be associated with poor trial outcomes. More research is necessary to further understand the specific mechanisms by which nutritional status and muscle mass may influence toxicity risk in this population.