Search

Conducting randomized controlled trials (RCTs) in patients with germline mutations in genes that predispose to adult-onset cancer is hampered by the rarity of these mutations, barriers to their identification, and challenges inherent to randomizing high-risk individuals as part of a clinical trial. Most of the clinically relevant RCTs have been conducted in 3 syndromes in only some of the high-risk genes for which clinical testing is currently available. This article reviews the surgical, screening, and chemoprevention RCTs in each of the syndromes in clinically relevant studies conducted in the past 10 years.

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. 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.

10592 Background: TGP identifies targets for precision cancer treatments. TGP may also identify secondary hereditary cancer risks, necessitating complex decision support during informed consent. ONCs are poorly trained in the communication of genetic information, particularly for patients with low health literacy, poor knowledge of genetics, and high medical mistrust. AA patients are especially vulnerable in this setting. Methods: We conducted semi-structured interviews with 10 ONCs to assess perceived barriers related to communication of secondary hereditary risks of TGP, probing barriers unique to AA patients. Informed by results, an Internet-based survey was developed/distributed to a convenience sample of 50 ONCs nationwide to assess TGP knowledge, genomics confidence, and perceptions related to communication of secondary hereditary risk. Results: Six themes emerged from interviews: risk/benefits of TGP, knowledge of genetics, discussing hereditary risk, value/harm of TGP, unique risks in AA, and training needs. Most ONCs felt uncomfortable discussing hereditary risks of TGP w/patients. Seven out of 10 identified socio-economic status, medical mistrust, discrimination, genetic counseling non-compliance, low health literacy and family relationships as factors important to consider with AA patients. Online survey participants were 52% White, 66% male, with median age of 42 years. Education in the interpretation/communication of TGP was largely informal (56% reported only informal training) and 46% reported perceived gaps in their education. Genomic confidence was associated w/higher use of TGP (p = 0.05), but was not associated w/knowledge or years in practice; however, low knowledge was associated w/more perceived barriers to TGP and w/negative attitudes toward the value of TGP and the challenge of communication of possible hereditary risks (p = 0.05). Early-career ONCs were more likely to endorse perceived barriers to communication of genetic risk information from TGP to AA patients. Overall 86% ONCs felt additional online training in communication of secondary hereditary risks of TGP would be useful. Conclusions: ONCs recognize unique needs and barriers for AAs related to communication of secondary hereditary genetic information from TGP. Many feel uncertain about how/whether to address barriers and recognize the need to improve their skillset to do so. Training is critical to ensure informed decision making in vulnerable populations.

e22527 Background: TGP is widely used to identify targetable mutations for precision cancer treatment and clinical trials. Many patients have poor understanding of TGP and are unaware of possible secondary hereditary risks. Lack of clarity regarding the relevance of informed consent and genetic counseling further magnify risks for patients. AA patients have lower genetic knowledge and health literacy and higher MM than Caucasian patients, making them especially vulnerable in the clinical setting. Perceptions of TGP in AA cancer patients have not been well-characterized. Methods: 120 AA pts from 1 suburban and 1 urban site (Fox Chase Cancer Center[FCCC] and Temple University Hospital[TUH]) were surveyed. A k-means cluster analysis using a modified MM scale was conducted; chi-square analysis assessed demographic differences. Perceptual mapping (PM)/multidimensional scaling and vector modeling was used to create 3-dimensional maps to study how TGP barriers/facilitators differed by MM group and how message strategies for communicating about TGP may also differ. Results: Data from 112 analyzable patients from FCCC (55%) and TUH (45%) were parsed into less MM (MM-L, n = 42, 37.5%) and more MM (MM-H, n = 70, 72.5%) clusters. MM-L and MM-H clusters were demographically indistinct with no significant associations by sex (p = 0.49), education (p = 0.3), income (p = 0.65), or location (p = 0.43); only age was significant (older = higher MM, p = 0.006). Patients in the MM-H cluster reported higher concerns about TGP, including cost (p < 0.001), insurance discrimination (p < 0.001), privacy breaches (p = 0.001), test performance/accuracy (p = 0.001), secondary gain by providers (p < 0.001) and provider ability to explain results (p = 0.04). Perceptual mapping identified both shared and contrasting barriers between MM clusters (Table). Conclusions: More than 2/3 of AA patients comprised a MM-H cluster. Communication strategies should focus on concerns about family and how to discuss TGP with an oncologist. PM can identify distinct and shared information needs of vulnerable populations undergoing TGP. [Table: see text]

49 Background: Substantial data support efficacy of ASA in colorectal adenoma and cancer (CRC) chemoprevention. In 2011, the CaPP2 Phase 3 trial showed benefit of 600 mg ASA daily for prevention of LS-associated CRC (HR 0.41,p=0.02) in persons w/ASA adherence >2 yrs. Anecdotally, uptake of ASA by LS pts has been low, but few data exist. We examined uptake and predictors of ASA chemoprevention among LS pts receiving follow-up at our center since 2011. Methods: Pts evaluated by Fox Chase’s Risk Assessment Program receive in-person medical recommendations and written information about cancer (CA) prevention measures including ASA. Medical records of 127 LS pts were retrospectively reviewed. Demographics, gene affected, personal Hx of CA, ASA use, and ASA dose were collected. Majority (94.5%) of cohort had documentation of ongoing LS endoscopic screening at our center—only 3.2% had no recent follow-up (past 3 yrs) and 2.4% had recently died (past 3 yrs). Chi-square tests and multivariable logistic regression were used in analyses. Results: Overall 24.4% (31/127) of pts reported ASA use for chemoprevention (see Table). Nearly half (48.4%) of ASA users took 81 mg ASA daily, and only 22.6% reported taking >600 mg ASA daily. ASA use was associated with older age, MLH1/ MSH2+ vs MSH6/ PMS2+, and personal Hx of CRC. In the multivariable logistic model, older age (OR 2.80, p=0.04) and MLH1/ MSH2+ (OR 2.64,p=0.07) were significant and borderline significant, respectively. Adding race/ethnicity and gender strengthened the effect of age>60 (OR 3.11, p=0.03), and improved fit (pseudoR2=16.8%). Conclusions: Uptake of ASA chemoprevention by LS pts is overall modest, but older age is associated with ASA uptake for chemoprevention. Among ASA users, fewer than 1 in 4 take the 600 mg daily dose shown effective in CaPP2. Confirmatory trials as well as efforts to elucidate barriers to ASA chemoprevention in LS are needed. [Table: see text]

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.

1536Background: Uptake of genetic evaluation (GE) remains limited in cancer pts. MGPT is recommended for GE of women with ovarian cancer (OC), but many will never be tested. For pts w/incident colo...

1513Background: uMMR of CRC/EC for Lynch syndrome (LS) is recommended to identify the 2-3% of incident CRC/EC with germline MMR mutations in MLH1, MSH2, MSH6, and PMS2. Many US centers use a positive immunohistochemical (IHC+) tumor test to prompt further evaluation such as genetic counseling (GC). Efficacy of uMMR is established, but real-world performance is not. W/recent Blue Ribbon Panel recommendations for broad implementation, we reviewed uMMR effectiveness in an academic cancer center. Methods: Outcomes of all CRC/EC undergoing uMMR from 9/2011 (start of uMMR at Fox Chase Cancer Center) to 12/2017 were reviewed. uMMR results are reported in the surgical pathology report and by email to providers w/a PDF test report meant for pts. Results [IHC, MSI, BRAF, MLH1 promoter methylation, gene testing] and clinical data were extracted from a clinical genetics database and the EMR. Associations were tested by chi-square and T-test (2-sided). Results: From 1156 screened tumors, 278 (24.0%) had +IHC: 112 (40....

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]

1587 Background: MGTP use in routine cancer (CA) care is likely to increase w/lower costs for NGS-based testing and growing numbers of actionable targets coupled with targeted therapeutics. Early MGPT uptake has been slow among community oncologists (COs) due to their lower confidence to order, interpret, and act upon results of MGTP. This study evaluated the provision of telephone genomic consultation (GC) via an academic clinician link to an institutional genomic tumor board to support MGTP testing of CA patients (PTs) by COs. Methods: 4 practices of COs participated: 9 COs recruited 25 PTs w/metastatic CA. All PTs/COs completed baseline and follow-up (FU) assessments. Tumor blocks were evaluated at Fox Chase Cancer Center (FCCC) and tested w/a 50-gene MGTP. 12% blocks were inadequate. MGTP results were presented when appropriate at FCCC’s Genomic Tumor Board. All MGTP yielded > 1 variant (Var) [range 1-6]: 13/22 (59%) pts tested had a clinically relevant V; 6 other Vars were potentially actionable w/ approved therapy, while 3 Vars have novel therapies in Phase I/II studies. MGTP were called out to COs (by MJH) < 2 wks of resulting. A tailored summary was provided to COs. Results: At baseline, COs (n = 9) had limited experience w/MGTP (78%, < 5 ordered). Barriers for COs were: poor understanding of MGTPs (67%), cost (89%), uncertain benefit (44%), and poor access to targeted therapies (67%). At FU, 4/8 (50%) COs found GC “very useful”, and 63% reported MGPT paired w/GC would “probably/definitely” increase their use of MGTPs. Most (88%) felt MGPTs should be offered to PTs w/incurable CA. Among PTs at baseline (n = 25), awareness of MGTP was moderate (50%), but 79% reported it would help doctors take better care of their PTs. Valuation of MGTP was mixed—30% would pay $0 out of pocket, yet 30% also said they would travel “any distance” for an MGT-targeted experimental therapy. At FU (n = 14), 86% PTs felt MGPT was valuable, yet only 46% would “definitely” retest, and only 31% would pay > $100 to retest, even for 500+ genes. Conclusions: GC can be effective to support COs to use MGTPs. PTs w/CA have high expectations of MGTPs to improve their care, and yet attribute modest value to retest or to have a larger MGTP.

e21700 Background: Cancer therapies undergo evaluation in P1/2 trials, frequently in patients (pts) with disrupted caloric intake, weight loss, and other adverse effects of cancer on physical and psychological functioning. CMN and sarcopenia may increase treatment related toxicity (TRT) due to acquired pharmacokinetic variability and altered drug metabolism. Little is known about the prevalence of CMN among pts enrolling on P1/2 trials, its association with abnormal physical and psychological functioning, and its role in mediating TRT. Methods: Pts initiating a P1/2 trial were recruited. Study acceptance rate was > 95%. Pts had a comprehensive nutritional assessment using the validated PG-SGA, a short, 3-5 minute tool that evaluates multiple nutritional domains [symptom burden, functional status, metabolic stress and physical exam (muscle/fat status)]. CMN is defined as a PG-SGA score of ≥ 9. Distress, anxiety, depression and physical activity were also measured. BMI and albumin were extracted from the chart. Statistical significance was determined by Fisher’s exact test. Results: 54 pts (85% P1) were enrolled. CMN was identified in 39%. Pts with gastrointestinal (GI) cancers were more likely to have CMN than non-GI cancers (75% vs 24%, p = 0.001); otherwise, CMN rates were not different by age ( < 60 vs 60+), gender, race, or trial phase (1 vs 2). CMN was also associated with number of lines of therapy, but was surprisingly less common among patients with > 2 therapies compared to those with 0-2 (29% vs 57%, p = 0.051). Strong associations of CMN to distress (p = 0.028), depression (p = 0.020) and sedentary lifestyle (p = 0.012) were also seen. Clinical “red flags” of MN such as low BMI ( < 25) and low albumin ( < 3.5) had poor sensitivity (66.7% and 33.3%) and specificity (57.6% and 78.8%) for CMN. Correlation of CMN to TRT is underway. Conclusions: CMN is prevalent among P1/2 trial pts, notably in those with GI cancers and with fewer lines of therapy, and is associated with physical inactivity, distress and depression. BMI and albumin are poorly predictive of CMN. Undiagnosed CMN may, through multiple pathways, increase the vulnerability of pts on P1/2 studies to TRT. Comprehensive nutritional assessment of P1/2 pts should be considered.

e13021Background: TGP has emerged as an increasingly routine part of treatment planning for cancer. Patients’ awareness and attitudes toward TGP, and the value they place on its impact remain uncer...

538 Background: TGP of cancers is increasingly accessible to oncologists (MDs) and patients (pts). Despite efforts to provide clinical interpretation and decision support within TGP reports, results are complex and their interpretation remains fraught with uncertainty. In an ongoing pilot, we provide community MDs access to a 50-gene next generation sequencing (NGS)-based TGP assay and expert guidance through remote access to genomic tumor board (GTB) resources via telephone-based GC. Our goal is to explore how access to GTB expertise impacts community patterns of care. In parallel, we examine MDs and pts perceptions of TGP with a focus on awareness and expectations. Methods: MDs from 4 community practices participated. Participating MDs and their pts with metastatic unresectable CRC receiving 2nd line or beyond chemotherapy provide informed consent and complete baseline and follow-up surveys. Adequate tumor samples are tested with the Fox Chase 50-gene NGS-based TGP assay. All results are presented at a bi-monthly GTB or are reviewed with the GTB chair. MDs have a ~10 min GC by telephone with the PI to summarize findings and convey GTB recommendations. Results: 9 MDs have enrolled 22 pts and TGP has been completed on 15 samples (4 additional in process and 3 insufficient for TGP). Pts report diverse ancestry (24% Hispanic or non-White) and SES (33% income < $25K). To date, all completed TGPs have reported > 1 mutation. Of 11 pts who have received TGP results, 1 has sought consultation at a tertiary center for a clinical trial. Pts with higher education were more aware of TGP (p = 0.05). Most (80%) pts felt TGP would improve their MD’s ability to treat their cancer. Male sex and higher education were associated with stronger belief that TGP will improve life expectancy. Conclusions: A partnership with community MDs to provide TGP and GTB expertise through GC is feasible. Pts exhibit high expectations of TGP, despite limited data to support improved outcomes from TGP-guided treatment. Further research into optimizing partnership between community MDs and tertiary centers is valuable to guide treatment and clinical trial participation based on TGP results.

e17635 Background: The potential to one day tailor all cancer treatments to a tumor’s genomic profile is an emerging reality due to the commercial availability of NGSGT. While healthcare providers ...