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Background Patients with advanced esophageal cancer carry poor prognoses; limited data exist to guide second-line therapy in the metastatic setting. Paclitaxel has been used yet is associated with limited efficacy. There is preclinical evidence of synergy between paclitaxel and cixutumumab, a monoclonal antibody targeting insulin-like growth factor-1 receptor. We conducted a randomized phase II trial of paclitaxel (arm A) versus paclitaxel plus cixutumumab (arm B) in the second-line for patients with metastatic esophageal or gastroesophageal junction (GEJ) cancers. Methods The primary endpoint was progression-free survival (PFS); 87 patients (43 in arm A, 44 in arm B) were treated. Results Median PFS was 2.6 months in arm A [90% CL 1.8-3.5] and 2.3 months in arm B [90% 2.0-3.5], P = .86. Stable disease was observed in 29 (33%) patients. Objective response rates for Arms A and B were 12% [90% CI, 5-23%] and 14% [90% CI, 6-25%]. Median overall survival was 6.7 months [90% CL 4.9-9.5] in arm A and 7.2 months [90% CL 4.9-8.1] in arm B, P = 56. Conclusion The addition of cixutumumab to paclitaxel in second-line therapy of metastatic esophageal/GEJ cancer was well tolerated but did not improve clinical outcomes relative to standard of care (ClinicalTrials.gov Identifier: NCT01142388).

Background The COVID-19 pandemic has led to delays in patients seeking care for life-threatening conditions; however, its impact on treatment patterns for patients with metastatic cancer is unknown. We assessed the COVID-19 pandemic’s impact on time to treatment initiation (TTI) and treatment selection for patients newly diagnosed with metastatic solid cancer. Methods We used an electronic health record–derived longitudinal database curated via technology-enabled abstraction to identify 14 136 US patients newly diagnosed with de novo or recurrent metastatic solid cancer between January 1 and July 31 in 2019 or 2020. Patients received care at approximately 280 predominantly community-based oncology practices. Controlled interrupted time series analyses assessed the impact of the COVID-19 pandemic period (April-July 2020) on TTI, defined as the number of days from metastatic diagnosis to receipt of first-line systemic therapy, and use of myelosuppressive therapy. Results The adjusted probability of treatment within 30 days of diagnosis was similar across periods (January-March 2019 = 41.7%, 95% confidence interval [CI] = 32.2% to 51.1%; April-July 2019 = 42.6%, 95% CI = 32.4% to 52.7%; January-March 2020 = 44.5%, 95% CI = 30.4% to 58.6%; April-July 2020 = 46.8%, 95% CI= 34.6% to 59.0%; adjusted percentage-point difference-in-differences = 1.4%, 95% CI = −2.7% to 5.5%). Among 5962 patients who received first-line systemic therapy, there was no association between the pandemic period and use of myelosuppressive therapy (adjusted percentage-point difference-in-differences = 1.6%, 95% CI = −2.6% to 5.8%). There was no meaningful effect modification by cancer type, race, or age. Conclusions Despite known pandemic-related delays in surveillance and diagnosis, the COVID-19 pandemic did not affect TTI or treatment selection for patients with metastatic solid cancers.

The NCCN Guidelines for Older Adult Oncology address specific issues related to the management of cancer in older adults, including screening and comprehensive geriatric assessment (CGA), assessing the risks and benefits of treatment, preventing or decreasing complications from therapy, and managing patients deemed to be at high risk for treatment-related toxicity. CGA is a multidisciplinary, in-depth evaluation that assesses the objective health of the older adult while evaluating multiple domains, which may affect cancer prognosis and treatment choices. These NCCN Guidelines Insights focus on recent updates to the NCCN Guidelines providing specific practical framework for the use of CGA when evaluating older adults with cancer.

Background Quinacrine plus a fluoropyrimidine has in vivo efficacy against metastatic colorectal cancer (mCRC). This phase 1b trial evaluated the combination of quinacrine plus capecitabine in patients with treatment-refractory mCRC. Patients and Methods Using a modified Simon accelerated titration design, adults with treatment-refractory mCRC were treated with capecitabine 1000 mg/m2 twice daily for 14/21-day cycle, and escalating doses of quinacrine 100 mg daily, 100 mg twice daily, and 200 mg twice daily for 21 days. The primary endpoint was identifying the maximum tolerated dose, determining tolerability and safety. In an expansion cohort, it was overall response rate and time to tumor progression (TTP). Results Ten patients (median age of 60 years) were treated in phase 1b. The first 2 quinacrine dosing levels were well tolerated. Dose-limiting toxicities were seen in 3 patients treated with quinacrine 200 mg twice daily. Five additional patients tolerated quinacrine 100 mg twice daily without further dose-limiting toxicities, thus establishing the maximum tolerated dose. Seven additional expansion-cohort patients enrolled onto the study before quinacrine manufacturing ceased within the United States. Five patients experienced stable disease, 1 partial response, and 10 disease progression. Median TTP overall was 2.12 months and median overall survival 5.22 months for the 17 patients. Conclusion Capecitabine and quinacrine can be safely administered at the maximum tolerated dose of capecitabine 1000 mg/m2 by mouth twice daily on days 1-14 and quinacrine 100 mg by mouth twice daily on days 1-21 of a 21-day cycle in mCRC patients. Although the expansion study was halted early, TTP was in line with other studies of refractory mCRC, suggesting activity of this regimen in heavily pretreated patients.

PURPOSE Limited tools exist to predict the risk of chemotherapy toxicity in older adults with early-stage breast cancer. METHODS Patients of age ≥ 65 years with stage I-III breast cancer from 16 institutions treated with neoadjuvant or adjuvant chemotherapy were prospectively evaluated for geriatric and clinical features predictive of grade 3-5 chemotherapy toxicity. Logistic regression with best-subsets selection was used to identify and incorporate independent predictors of toxicity into a model with weighted variable scoring. Model performance was evaluated using area under the ROC curve (AUC) and goodness-of-fit statistics. The model was internally and externally validated. RESULTS In 473 patients (283 in development and 190 in validation cohort), 46% developed grade 3-5 chemotherapy toxicities. Eight independent predictors were identified (each assigned weighted points): anthracycline use (1 point), stage II or III (3 points), planned treatment duration > 3 months (4 points), abnormal liver function (3 points), low hemoglobin (3 points), falls (4 points), limited walking (3 points), and lack of social support (3 points). We calculated risk scores for each patient and defined three risk groups: low (0-5 points), intermediate (6-11 points), or high (≥ 12 points). In the development cohort, the rates of grade 3-5 chemotherapy toxicity for these three groups were 19%, 54%, and 87%, respectively ( P < .01). In the validation cohort, the corresponding toxicity rates were 27%, 45%, and 76%. The AUC was 0.75 (95% CI, 0.70 to 0.81) in the development cohort and 0.69 (95% CI, 0.62 to 0.77) in the validation cohort. Risk groups were also associated with hospitalizations and reduced dose intensity ( P < .01). CONCLUSION The Cancer and Aging Research Group-Breast Cancer (CARG-BC) score was developed and validated to predict grade 3-5 chemotherapy toxicity in older adults with early-stage breast cancer.

Background Despite national guideline recommendations for universal biomarker testing (KRAS, NRAS, BRAF, and mismatch repair and microsatellite instability [MMR/MSI]) in all patients with metastatic colorectal cancer (mCRC), little is known regarding adherence to these recommendations in routine practice. Methods We retrospectively reviewed patients with mCRC diagnosed between January 1, 2013, and December 27, 2018, from a de-identified electronic health record–derived database. We analyzed disparities in KRAS, NRAS, BRAF, and MMR/MSI testing by race, age, sex, and insurance status using χ2 tests and t tests. We evaluated changes in biomarker testing over time with attention to changes around dates of landmark publications and guideline updates using χ2 tests and Cochran-Armitage tests. Results A total of 20 333 patients were identified of which 66.6% had test results for any biomarker. Rates of test results for all 4 biomarkers statistically significantly increased over time (P Conclusions Increased rates of documented testing for NRAS, BRAF, and MMR/MSI in mCRC was seen between 2013 and 2018 reflecting adoption of guideline recommendations. However, the rate of documented testing remains lower than expected and warrants additional research to understand the extent to which this may represent a clinical practice quality concern.

BACKGROUND: Gauging fitness remains a challenge among older adults with hematologic malignancies, and interventions to restore function are lacking. We pilot a structured exercise intervention and novel biologic correlates of aging using epigenetic clocks and markers of immunosenescence to evaluate changes in function and clinical outcomes. METHODS: Older adults (n=30) with hematologic malignancy actively receiving treatment were screened and enrolled in a 6-month exercise intervention, the Otago Exercise Programme (OEP). The impact of the OEP on geriatric assessment metrics and health-related quality of life were captured. Clinical outcomes of overall survival and hospital utilization (inpatient length of stay and emergency department use) in relationship to geriatric deficits were analyzed. RESULTS: Older adults (median age, 75.5 years [range, 62–83 years]) actively receiving treatment were enrolled in the OEP. Instrumental activities of daily living and physical health scores (PHS) increased significantly with the OEP intervention (median PHS: visit 1, 55 [range, 0–100]; visit 2, 70 [range, 30–100]; P

Background Neoadjuvant chemoradiation (nCRT) followed by esophagectomy is the standard treatment for locally advanced esophageal cancer. Older patients are often felt to be poor candidates for nCRT. Limited data is available to guide the use of nCRT in this population. Methods A retrospective review of patients treated at a tertiary cancer center between 2002 and 2014 was conducted grouping patients by age (≥ 65 or Results 125 patients were identified for this study (67 aging Conclusions Older patients who underwent nCRT followed by esophagectomy had similar toxicities and outcomes as younger patients suggesting that nCRT before esophagectomy is safe in select older adults with esophageal cancer. PLR and NLR may serve as prognostic markers of aging, toxicity, and outcomes. Further research is warranted to optimize the therapy of older patients with this disease.

Background Metastatic high-grade neuroendocrine neoplasms (G3NENs) have limited treatment options after progression on platinum-based therapy. We addressed the role of Pembrolizumab in patients with previously treated metastatic G3NENs. Methods Two open-label, phase 2 studies enrolled patients with G3NEN (Ki-67 > 20%) to receive Pembrolizumab at 200 mg I.V. every 3 weeks. Radiographic evaluation was conducted every 9 weeks with overall response rate as the primary endpoint. Results Between November 2016 and May 2018, 29 patients (13 males/16 females) with G3NENs were enrolled. One patient (3.4%) had an objective response and an additional six patients (20.7%) had stable disease, resulting in a disease control rate of 24.1%. Disease control rate (DCR) at 18 weeks was 10.3% (3/29). There was no difference in the DCR, PFS or OS between the PD-L1-negative and -positive groups (p 0.56, 0.88 and 0.55, respectively). Pembrolizumab was well tolerated with only 9 grade 3, and no grade 4 events considered drug-related. Conclusions Pembrolizumab can be safely administered to patients with G3NENs but has limited activity as a single agent. Successful completion of our trials suggest studies in G3NENs are feasible and present an unmet need. Further research to identify active combination therapies should be considered. Clinical trial registration number NCT02939651 (10/20/2016).

PURPOSE Platinum-based therapy is the standard of care in patients who have HER2-negative, advanced esophagogastric cancer (AEGC). Retrospective data suggest that intratumoral ERCC1 levels may determine platinum sensitivity. A randomized, phase II study was performed in patients with AEGC to explore whether the efficacy of a platinum-based therapy with fluorouracil, leucovorin, and oxaliplatin (FOLFOX) versus a non–platinum-containing regimen of irinotecan and docetaxel (IT) differed according to ERCC1 levels. PATIENTS AND METHODS Overall, 202 untreated patients with HER2-negative AEGC and a Zubrod performance status of 0-1 were evaluated prospectively for mRNA expression of ERCC1 level and then randomly assigned to FOLFOX or IT, stratified by the intratumoral statuses of ERCC1 low (< 1.7) or high (≥ 1.7). Objectives were to assess progression-free survival (PFS) and overall survival (OS) in all patients treated with FOLFOX compared with IT, stratified by low and high ERCC1 levels, and to assess for interactive effects between ERCC1 expression and treatment arm. RESULTS Eighty-six percent of patients had ERCC1 values < 1.7. Thus, evaluation of the ERCC1-high subgroup was limited. Grade ≥ 3 anemia, dehydration, diarrhea, and fatigue were greater in patients with IT. Occurrences of grade ≥ 3 neuropathy and decreased neutrophils were greater in patients with FOLFOX. In all patients, FOLFOX had a statistically superior median PFS compared with IT (5.7 v 2.9 months; hazard ratio, 0.68; P = .02). In patients with ERCC1 levels < 1.7 receiving FOLFOX, PFS and response rate were statistically superior to IT, with no significant difference in OS. CONCLUSION The evaluation of ERCC1 in patients with upper GI tumors was thwarted by an overwhelming predominance of low ERCC1 mRNA expression. Nonetheless, distribution of treatment effects on PFS did not vary with expression. For all patients and for those with low ERCC1 expression, FOLFOX was superior in efficacy to IT.

723 Background: Active modification of surrounding stroma is a critical mechanism of tumor cell growth in pancreatic ductal adenocarcinoma (PDAC). There is some early translational evidence that losartan (L) and vitamin D (D) may affect the tumor microenvironment and supportive stroma in PDAC to help restore a physically and biologically tumor-suppressive stroma. These effects of potentially stroma-modifying drugs have not been established in the clinical management of metastatic PDAC (mPDAC), where there have been limited advances in treatment and prognosis remains poor. Methods: This is a single center, retrospective analysis of patients with mPDAC treated at Fox Chase Cancer Center from 2010 to 2019. All data including L and D use were extracted from the medical record. Patient characteristics were compared across subgroups using Chi-square tests, Fisher’s exact tests, and Wilcoxon rank sum tests. The primary outcome was overall survival (OS) from the time of metastatic diagnosis. Kaplan-Meier curves and log-rank tests were used to compare unadjusted OS across subgroups. Cox proportional hazards models were used to characterize OS adjusted for age at metastatic diagnosis, sex, initial stage at diagnosis, performance status, Charlson Comorbidity Index (CCI), hypertension, and renal disease. Results: 518 patients were included; a majority were male (54.1%), White (82.4%), and diagnosed with de novo mPDAC (54.6%). About half of patients had hypertension (53.5%) and few had renal dysfunction (5.6%). 153 (29.5%) patients were taking D and 41 (8%) patients were taking L. Women were more likely to take D than men (p < 0.001) and White patients were more likely to take L than other races/ethnicities (p = 0.006). Median OS since metastatic diagnosis for patients taking L was 11.4 months compared to 9.6 months for patients not taking L (p = 0.07). Median OS for patients taking D was 11.3 months compared to 8.7 months for those not taking D (p = 0.10). A Cox proportional hazards model adjusting for confounders, however, showed that both L (HR 0.66, p = 0.02) and D (HR 0.81, p = 0.04) were significantly associated with improved OS from time of metastatic diagnosis. Conclusions: This large retrospective study demonstrates potential clinical and survival benefit of L and D in conjunction with mPDAC treatment. L and D are safe, well tolerated, and widely used in general medical practice. These results support further investigation of the stroma-modifying potential of L and D, as well as conducting prospective trials with these agents to further validate these findings.

496 Background: Hepatocellular carcinoma (HCC) disproportionately affects minorities, particularly Black and Hispanic patients, and patients of lower socioeconomic status. These patients are more likely to be diagnosed with advanced disease, less likely to receive curative therapies, and have higher mortality rates. Data on the impact of disparities on patterns of systemic treatment (STx) in these disadvantaged groups are limited. This retrospective observational study used a large real-world database to explore differences in patient characteristics and patterns of STx based on race/ethnicity (R/E) and insurance status. Methods: 1283 patients diagnosed with HCC from 2011 to 2021 with known race, insurance, documented metastatic disease (mHCC), and without prior transplant from the nationwide de-identified Flatiron Health EHR-derived database were selected and analyzed. Chi-squared tests, T-tests, and log-rank tests were used to assess how R/E and insurance (Medicaid vs non-Medicaid) were related to HCC risk factors, number of lines of systemic therapy (LOT), and time from metastatic diagnosis (mDx) to start of STx. Results: Of 1283 patients evaluated, there were 750 white (W), 175 Black (B), 122 Hispanic (H), 69 Asian (A), and 167 patients with other race. B and H patients had the highest rates of known HCV (B 74.3%, H 48.4%, W 41.2%, A 23.2%; p < 0.001) and A patients were most likely to have known HBV (53.6%). More B and H patients had Medicaid (W 10.9%, A 14.3%, B 18.9%, H 28.5%, p < 0.001) and had the lowest rates of Medicare with commercial insurance (W 25.9%, A 21.7%, B 12.6%, H 14.6%, p < 0.001). H patients had the lowest rates of commercial insurance (H 39.3%, W 41.3%, A 44.9%, B 44.6%, p < 0.001). There was no significant difference in likelihood of receiving approved STx after mDx based on R/E. A patients had the highest rates of receiving multiple LOT (A 37.5%, W 18.5%, B 18.9%, H 20.5%; p = 0.285). 30-40% of patients with mHCC did not receive any STx and only 18-27% received more than 1 LOT. Most patients received STx for mHCC within 2 months without a significant difference based on R/E. There was no difference in unadjusted time to treatment based on insurance. Conclusions: This large-scale analysis did not reveal significant differences in the likelihood of receiving STx after mDx based on R/E or insurance. This analysis has limited data from safety net hospitals, which may impact our ability to fully elucidate disparities in the medical management of advanced HCC. 30-40% of patients with mHCC did not receive any STx and only 18-27% received more than 1 LOT, indicating that a significant portion of patients with HCC may be undertreated even in academic and community practice settings. Large scale real-world database analysis is a critical way to better understand treatment and survival outcomes in this population, which is expected to have the highest rates of HCC over the next 10 years and has been underrepresented in HCC trials.

699 Background: Outcomes of older adults with pancreatic cancer are highly variable with increased susceptibility to chemotherapy toxicities and inferior survival compared to younger patients. Determining which older adults are at higher risk for adverse outcomes remains a clinical challenge. We evaluated the association of a novel patient-reported geriatric assessment (GA)-based frailty index with survival among older adults with pancreatic cancer. Methods: Older adults (≥60y) referred for initial consultation at the UAB GI oncology clinic were prospectively enrolled in the Cancer and Aging Resilience Evaluation (CARE) registry. All patients underwent a patient-reported GA capturing multiple aging-related domains of health. The 44-item CARE frailty index (CARE-FI) based on the principles of deficit accumulation was utilized to determine frailty. The primary outcome was overall survival (OS) from the time of GA. Kaplan Meier method was used to estimate OS and comparisons between groups were by log-rank. A multivariate Cox regression model adjusted for age, sex, race, and cancer stage. Results: A total 254 older adults with pancreatic cancer were included; median age 70y, 52.4% male, 77% non-Hispanic white and 43.4% with stage IV disease. Overall, 40.1% (n=102) were frail, 26.0% (n=66) pre-frail and 33.9% (n=86) robust. No significant clinico-demographic differences across the 3 frailty groups were found. Differences in OS over two-year period was observed across the three frailty groups by the KM method ( p=0.008). In multivariate cox regression, frail status was associated with an increased risk of mortality (HR 1.9 [95% CI 1.19 – 2.98]; p=0.01) compared to robust status after adjustment for aforementioned confounders. Conclusions: The CARE-FI is a novel frailty index built on the principles of deficit accumulation using a patient-reported GA and is independently associated with survival among older adults with pancreatic cancer.[Table: see text]

Simple Summary Selection of appropriate stage II colon cancer patients for adjuvant chemotherapy (AC) is controversial. A novel immune response classifier has previously been validated to refine patient selection, but its impact on oncologist treatment planning had yet to be described. In this survey, all but one oncologist altered clinical practice recommendations, and recommendations for AC prescriptions were reduced by half (among the Immunoscore-high cases (low recurrence risk)). This study revealed that the Immunoscore results could significantly decrease AC use in patients with stage II colon cancer who may not benefit from it, thereby reducing the administration of nonvalue care. Abstract Background: Adjuvant chemotherapy use in stage II colon cancer is controversial. Current prognostic risk factors do not take the tumor immune microenvironment into account. Consideration of the Immunoscore, which measures the host immune response at the tumor site, may assist clinicians in reducing adjuvant chemotherapy use in patients who are unlikely to benefit from it. This study sought to determine the potential clinical utility of the Immunoscore, via its effect on medical oncologists’ recommendations for management of patients with stage II colon cancer. Methods: De-identified vignettes of 10 patients with stage II colon cancer were presented to 25 practicing medical oncologists. Each participant completed surveys indicating recommendations for adjuvant chemotherapy and surveillance strategies. An educational session was subsequently conducted, and the same patient profiles were re-presented but included immunoscore results. Participants were again asked to provide their recommendations. A participant was counted as influenced if their responses were altered after immunoscore test results were provided. Results: All but one participant (96%) altered a management recommendation for ≥1 case. For individual cases, a mean of 55% (range, 40–80%) of participants altered their recommendations for adjuvant chemotherapy and/or surveillance. For the immunoscore-high cases (low-risk of recurrence), recommendations for adjuvant chemotherapy use decreased from 60% to 31%. Conclusions: These results indicate a willingness by oncologists to integrate immunoscore information into clinical practice recommendations. Incorporation of immunoscore data resulted in the reduction of nonvalue care in the simulated population. Confirmation in prospective studies is planned.

Background: Elevated circulating growth differentiation factor 15 (GDF15) and increased GDF15 expression in tumor tissues has been observed in patients with advanced pancreatic cancer (APC). These changes were correlated with poor survival. Effects of GDF15 on tumor progression, metastasis and immune escape may play a role. NGM120, a novel antibody to GFRAL that blocks the effects of GDF15, has resulted both in antitumor and anti-cachexia effects in experimental models. Here we report updated findings of the ongoing Phase 1b study with NGM120 in patients with APC. Methods: Metastatic pancreatic cancer patients with elevated serum GDF15 were treated with NGM120 (30 or 100 mg, s.c., q4wks) in a 1st line setting in combination with Gem/nab-paclitaxel. Primary endpoints were safety and tolerability. Secondary endpoints were pharmacokinetics, preliminary evidence of antitumor activity (RECIST) and anti-cachexia effects. Results: Eight patients received NGM120 in combination with Gem/nab-paclitaxel. Median age was 67 years, all patients had advanced disease. NGM120 was well tolerated with no dose-limiting toxicities. Most of the AEs or SAEs observed were Gem/nab-paclitaxel related and none of them attributed to NGM 120 treatment. As of data cut off on March 25, 2022, preliminary results include 3 patients with PR (extending >32 wks), 3 patients SD; 2 patients discontinued early (before first post-dose scan) due to toxicity attributed to Gem/nab-paclitaxel. Among the 6 evaluable patients, the disease control rate (DCR) is 100%, mPFS has not been reached, 12-month survival rate (12-month OS) is 83.3%. Over the course of the study, 5/6 of the patients gained or maintained their body weight (BW) and 5/6 of the patients gained or maintained their lean body mass (LBM) based on maximum change from baseline. Conclusions: NGM120 given in combination with Gem/nab-paclitaxel to patients with APC resulted in a 50% ORR (3 PR in 6 evaluable patients), 100% DCR, 83.3% 12-month OS and a “not reached” mPFS. Compared to historical Gem/nab-paclitaxel data, these findings are encouraging and support the potential role of NGM120 in the treatment of patients with APC. The positive effects on BW and LBM is also encouraging compared to the historical cachexia rate of 30% observed within 12 weeks of starting first-line chemotherapy in APC. A sign of NGM120 engages the GDF15-GFRAL pathway in managing body weight regulation. A Ph2a study is ongoing to further evaluate NGM120 in combination with Gem/nab-paclitaxel in the 1st line setting for the treatment of APC. Citation Format: Andrew Hendifar, Efrat Dotan, Benjamin Weinberg, Edward Kim, Peter Hosein, Jian Luo, Jiping Zha, Alex DePaoli, Vladimir Hanes, Cecilia Tranmuchowski, Kefei Zhou, Carol Tseng, Hsiao Lieu. Initial results of a cohort of advanced pancreatic cancer patients in a phase 1b Study of NGM120, a first-in-class anti-GDNF Family Receptor Alpha Like (GFRAL) antibody [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer; 2022 Sep 13-16; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2022;82(22 Suppl):Abstract nr PR006.

340 Background: Gastrointestinal oncology patients (GIOP) at Fox Chase Cancer Center (FCCC) disproportionately require emergency department (ED) or urgent care (UC) evaluation due to chemotherapy-related adverse events (CRAE). Between January 2014 - June 2018, GIOP comprised 24% of visits to the FCCC ED and 29% of visits to the FCCC UC center, though specific patient and disease characteristics are unavailable. Prior to March 2022 there was no process to proactively contact patients to assess for CRAE or provide symptom management education (SME) following the administration of a new intravenous chemotherapy (IVC). This contributed to a perception of higher volumes of patient-initiated phone calls for acute CRAE management, SME, and UC/ED evaluations as compared to other disease sites, leading to patient and provider dissatisfaction. Methods: We aimed to contact at least 50% of all GIOP starting new IVC through a standardized nurse-initiated phone call within 72 hours of a patient’s first infusion by June 2022. A multidisciplinary team of medical oncology fellows, nurses, and clinic managers launched this initiative through participation in the ASCO Quality Training Program. A series of Plan-Do-Study-Act (PDSA) cycles were conducted over 12 weeks. All GIOP starting a new IVC were electronically identified on a weekly basis by the infusion room scheduling system. Clinic nurses called patients from this list to assess symptoms, provide SME, and advise early intervention for CRAE. A smart phrase was developed for efficient yet comprehensive documentation in the electronic medical record (EMR). EMR documentation was reviewed weekly to determine if calls were made within 72 hours of treatment, which guided subsequent PDSA cycles. Results: From March 14, 2022 to June 3, 2022, a list of all GIOP starting a new IVC was generated and consistently distributed weekly to nurses embedded in 6 GI oncology clinics. Over 12 weeks, 40 (56%) of 71 patients receiving a new IVC were called and 37 (52%) of the patients were called within 72 hours. Of the patients who were called, 93% were called within the intended time frame. Nurses documented their outreach calls in the EMR utilizing a standardized smart phrase to summarize CRAE assessments and SME. Acute or unresolved issues were triaged to the patient’s primary oncology team for further guidance. Conclusions: This initiative successfully introduced a nursing-led outreach phone call to GIOP starting a new IVC, though additional PDSA cycles are needed to achieve more consistent outreach. We plan to standardize outreach to patients with organized SME while striving to automate performance monitoring. Further evaluation of this intervention, which will eventually better identify patients at highest risk for acute unplanned care needs, will assess the impact of patient-reported outcomes and health care utilization.

Background Gemcitabine and nab-paclitaxel (GA) is a first-line treatment for patients with metastatic pancreatic cancer (mPDAC). The traditional dosing schedule of GA is days 1, 8, and 15 of a 28-day cycle. Frequently, older adults are given a modified dosing schedule using 2 doses per cycle because of toxicity. We retrospectively analyzed treatment patterns and outcomes of older adults with mPDAC given these 2 dosing schedules. Methods Patients 65 years or older with mPDAC treated with GA in a nationwide real-world database between January 1, 2014, and May 31, 2019, were included. Demographic, disease, and treatment information were collected. Patients were grouped by dosing at treatment initiation (traditional vs modified dosing schedules). Endpoints were time on treatment (TOT) and overall survival (OS) in patients receiving at least 2 cycles. All statistical tests were 2-sided. Results 1317 patients were included (traditional dosing schedule: n = 842; modified dosing schedule: n = 475). Median age at diagnosis was 72 and 73 years for traditional and modified dosing schedules, respectively (P < .001), but sex, race, and performance status were not statistically significantly different. The median TOT and OS were better for the traditional vs modified dosing schedule (unadjusted median TOT, first-line = 4.18 vs 3.26 mo, P =.04; OS = 9.44 vs 7.63 mo, P =.003). Conclusion In this real-world cohort, treatment of older mPDAC patients with a modified dosing schedule of GA resulted in shorter TOT and worse OS vs a traditional dosing schedule. With the caveats of potential confounding that exist in a nonrandomized retrospective database, these results suggest that dose intensity may be important, and prospective studies are necessary to ensure we treat our patients most effectively.

Older patients make up the majority of patients with pancreatic cancer, with a median age of 71 years at diagnosis. However, older patients are underrepresented in clinical trials in pancreatic cancer. This study investigates trends in age distribution of patients enrolled in clinical trials for advanced pancreatic cancer over time, and examines outcomes and toxicity in older patient subgroups from two studies conducted by Eastern Cooperative Oncology Group and American College of Radiology Imaging Network (ECOG-ACRIN) in this disease.16,042 patients from 38 phase III clinical trials for locally advanced or metastatic pancreatic adenocarcinoma published between 1997 and 2016 were identified and included in this analysis. Outcomes and toxicity by age were examined in two of the trials, ECOG-ACRIN trials E2297 and E6201, which included a total of 1146 patients.The median age across the trials was 62.7 years; median ages for individual trials ranged from 57 years to 66 years. Weighted linear regression showed no significant change in median age over time. Combined analysis of the two ECOG-ACRIN trials demonstrated higher rates of fatigue, thrombocytopenia, and infection in those ≥75 years compared with those75 years, but despite this showed no difference in overall survival (OS) or progression-free survival (PFS) (OS: 5.7 vs. 5.6 months and PFS: 2.8 vs 3.5 months).Enrollment of older adults in phase III pancreatic cancer clinical trials has not increased over time, despite increasing number of older patients seen in clinic. Increased efforts are needed to enhance enrollment of older patients in clinical trials, and to promote trials specifically for older patients, in order to improve the evidence base for treating this patient population.

SummaryVantictumab is a fully human monoclonal antibody that inhibits Wnt pathway signaling through binding FZD1, 2, 5, 7, and 8 receptors. This phase Ib study evaluated vantictumab in combination with nab-paclitaxel and gemcitabine in patients with untreated metastatic pancreatic adenocarcinoma. Patients received vantictumab at escalating doses in combination with standard dosing of nab-paclitaxel and gemcitabine according to a 3 + 3 design. A total of 31 patients were treated in 5 dosing cohorts. Fragility fractures attributed to vantictumab occurred in 2 patients in Cohort 2 (7 mg/kg every 2 weeks), and this maximum administered dose (MAD) on study was considered unsafe. The dosing schedule was revised to every 4 weeks for Cohorts 3 through 5, with additional bone safety parameters added. Sequential dosing of vantictumab followed by nab-paclitaxel and gemcitabine was also explored. No fragility fractures attributed to vantictumab occurred in these cohorts; pathologic fracture not attributed to vantictumab was documented in 2 patients. The study was ultimately terminated due to concerns around bone-related safety, and thus the maximum tolerated dose (MTD) of the combination was not determined. The MAD of vantictumab according to the revised dosing schedule was 5 mg/kg (n = 16).

The NCCN Guidelines for Pancreatic Adenocarcinoma discuss the diagnosis and management of adenocarcinomas of the exocrine pancreas and are intended to assist with clinical decision-making. These NCCN Guidelines Insights discuss important updates to the 2019 version of the guidelines, focusing on postoperative adjuvant treatment of patients with pancreatic cancers.

Cholangiocarcinomas are rare tumors originating at any point along the biliary tree. These tumors often pose significant challenges for diagnosis and treatment, and often carry a poor prognosis. However, in recent years, studies have identified significant molecular heterogeneity with up to 50% of tumors having detectable mutations, leading to the guideline recommendations for molecular testing as part of the diagnostic workup for these tumors. In addition, better classification of these tumors and understanding of their biology has led to new drugs being approved for treatment of this resistant tumor. This manuscript will provide a comprehensive review of the epidemiology, risk factors, diagnostic approach, molecular classification, and treatment options for patients with advanced cholangiocarcinomas.

OPINION STATEMENT Pancreatic cancer is increasing in incidence in the USA. This disease disproportionately affects older adults, and as the percentage of adults > 65 years old increases with the aging of the baby boomers, the prevalence is expected to rise over the coming decade. These patients are often more susceptible to disease-related symptoms and have less ability to withstand both cancer and treatment-related side effects. Therefore, it is imperative that treating physicians thoughtfully consider their recommended treatment approach towards this vulnerable patient population. This review focuses on the current state of research of older adults with pancreatic adenocarcinoma, highlighting deficiencies in the representation of this patient population in clinical trials. It is vital that the treating physicians take a nuanced approach towards therapy of localized and metastatic disease in geriatric patients. A one size fits all treatment algorithm is no longer appropriate in any cancer patient, let alone the elders who are particularly vulnerable to developing treatment-related toxicities. To help guide therapy decisions, it is important to perform a comprehensive geriatric assessment which may uncover unexpected frailty and lead to a change in the recommended treatment approach. In this way, we can support older adults during therapy for this aggressive malignancy and provide optimal care.

Pancreatic cancer is the fourth leading cause of cancer-related death among men and women in the United States. A major challenge in treatment remains patients’ advanced disease at diagnosis. The NCCN Guidelines for Pancreatic Adenocarcinoma provides recommendations for the diagnosis, evaluation, treatment, and follow-up for patients with pancreatic cancer. Although survival rates remain relatively unchanged, newer modalities of treatment, including targeted therapies, provide hope for improving patient outcomes. Sections of the manuscript have been updated to be concordant with the most recent update to the guidelines. This manuscript focuses on the available systemic therapy approaches, specifically the treatment options for locally advanced and metastatic disease.

IMPORTANCE: Immunotherapy has been associated with improved outcomes among patients who have received previous treatment for microsatellite instability–high (MSI-H) tumors. OBJECTIVE: To evaluate the antitumor activity of pembrolizumab therapy vs chemotherapy among patients with MSI-H advanced gastric or gastroesophageal junction (G/GEJ) cancer regardless of the line of therapy in which it was received. DESIGN, SETTING, AND PARTICIPANTS: This post hoc analysis of the phase 2 KEYNOTE-059 (third-line treatment or higher) single-arm trial and the phase 3 KEYNOTE-061 (second-line treatment) and KEYNOTE-062 (first-line treatment) randomized trials included patients with advanced G/GEJ cancer from 52 sites in 16 countries enrolled in KEYNOTE-059, 148 sites in 30 countries enrolled in KEYNOTE-061, and 200 sites in 29 countries enrolled in KEYNOTE-062. Patients were enrolled from March 2, 2015, to March 26, 2016, in KEYNOTE-059; from June 4, 2015, to July 26, 2016, in KEYNOTE-061; and from September 18, 2015, to May 26, 2017, in KEYNOTE-062, with data cutoff dates of August 8, 2018; October 26, 2017; and March 26, 2019; respectively. INTERVENTIONS: Pembrolizumab monotherapy in KEYNOTE-059, pembrolizumab monotherapy or chemotherapy (paclitaxel) in KEYNOTE-061, and pembrolizumab monotherapy, pembrolizumab plus chemotherapy (cisplatin and 5-fluorouracil or capecitabine), or chemotherapy alone in KEYNOTE-062. MAIN OUTCOMES AND MEASURES: Response was assessed centrally using Response Evaluation Criteria in Solid Tumours (RECIST), version 1.1; MSI-H status was determined centrally by polymerase chain reaction testing. RESULTS: At data cutoff, 7 of 174 patients (4.0%) in KEYNOTE-059, 27 of 514 patients (5.3%) in KEYNOTE-061, and 50 of 682 patients (7.3%) in KEYNOTE-062 had MSI-H tumors. Among those with MSI-H tumors, the median overall survival was not reached (NR) for pembrolizumab in KEYNOTE-059, KEYNOTE-061, and KEYNOTE-062 or for pembrolizumab plus chemotherapy in KEYNOTE-062. The median progression-free survival (PFS) for pembrolizumab was NR (95% CI, 1.1 months to NR) in KEYNOTE-059 and 17.8 months (95% CI, 2.7 months to NR) in KEYNOTE-061 (vs 3.5 months [95% CI, 2.0-9.8 months] for chemotherapy). In KEYNOTE-062, the median PFS was 11.2 months (95% CI, 1.5 months to NR) for pembrolizumab, NR (95% CI, 3.6 months to NR) for pembrolizumab plus chemotherapy, and 6.6 months (95% CI, 4.4-8.3 months) for chemotherapy. The objective response rate (ORR) for pembrolizumab was 57.1% in KEYNOTE-059 and 46.7% (vs 16.7% for chemotherapy) in KEYNOTE-061. In KEYNOTE-062, the ORR was 57.1% for pembrolizumab , 64.7% for pembrolizumab plus chemotherapy, and 36.8% for chemotherapy. CONCLUSIONS AND RELEVANCE: Findings from this study indicate that MSI-H status may be a biomarker for pembrolizumab therapy among patients with advanced G/GEJ cancer regardless of the line of therapy in which it was received. TRIAL REGISTRATION: ClinicalTrials.gov Identifiers: NCT02335411, NCT02370498, and NCT02494583

Purpose/objective(s) Reirradiation (RI) can cause significant toxicity. BID-RT is a known regimen for rectal cancer recurrence. PLDR-RT is a promising alternative in which doses are delivered in pulses of small doses, with an effective rate of 0.07 Gy/minute. PLDR-RT widens the therapeutic window by making use of poor repair mechanisms of tumor cells. A previous phase I trial demonstrates its safety. We compared toxicity and local control between BID-RI and PLDR-RI of anorectal cancers. Materials/methods This is a single institutional IRB-approved retrospective review of patients previously treated with pelvic RT who underwent BID-RI or PLDR-RI for rectal or anal cancers between 2005-2020. Wilcoxon rank-sum and Fisher's exact tests were used to compare continuous and categorical variables. Common Terminology Criteria for Adverse Events (CTCAE) v5.0 was used to grade toxicities. Univariable logistic regression was used to assess the association between toxicity Grade ≥2 and radiation modalities. Cumulative incidence function was used to estimate local progression distribution. Difference between modalities and dose groups was compared using Chi-square tests. Results Twenty-six patients were included, with 24 rectal and 2 anal cancers. Median age was 59. 73% were males. 11 were in the BID-RI and 15 in PLDR-RI cohorts. Concurrent chemotherapy was more prevalent with BID-RI (81.8 vs. 33.3%; P = 0.021). No differences in age, sex, incidence or post-RT surgery were present. Median EQD2 of previous RT were 50 and 49.6 Gy (P = 0.60). PLDR-RI had higher total EQD2 (103.6 vs. 87.4 Gy; P = 0.07), median RI dose (50 vs. 39 Gy; P = 0.009), and proportion with RI dose ≥50 Gy (66.7 vs. 18.2%; P = 0.021). BID-RI had higher incidence of any grade GI/GU toxicity (81.8 vs. 33.3%; P = 0.021) (Table 1). PLDR-RI had no grade ≥3 GI and grade 4 toxicities. PLDR-RI was less likely to have any toxicity (OR = 0.15, CI:0.02-0.94, P = 0.04) and GI/GU toxicity (OR = 0.11, CI:0.02-0.72, P = 0.02). PLDR-RI trended toward less likelihood of grade ≥2 GI/GU toxicity (OR = 0.21; P = 0.07). No differences in local progression-free survival alone (0.66) or with death as a competing risk (P = 0.22) were found. Dose ≥50 Gy had no impact on local progression (P = 0.62). Conclusion PLDR-RI of anorectal cancers appears to demonstrate a significant improvement in incidence and severity of toxicity compared to BID-RI. This is possible without compromising local progression-free survival. Increased utilization of PLDR-RI may be indicated.

Background Geriatric assessment (GA) is recommended for evaluating fitness of an older adult with cancer. Our objective was to prospectively evaluate the gaps that exist in the assessment of older adults with metastatic breast cancer (OA-MBC) in community practices (CP). Methods Self-administered GA was compared to provider’s assessment (PA) of patients living with MBC aged ≥65 years treated in CP Providers were blinded to the GA results until PA was completed. McNemar’s test was used to detect differences between PA and GA. Results One hundred patients were enrolled across 9 CP (median age 73.9). Geriatric assessment detected a total of 356 abnormalities in 96 patients; of which, 223 required interventions. African American and widowed/single patients were more likely to have abnormalities identified by GA. On average, across 100 patients, PA did not detect 25.5% of GA-detected abnormalities, mostly in functional status, social support, nutrition, and cognition. These differences were less pronounced among providers with more clinical experience. Patients with abnormal Timed Up and Go tests more likely had additional abnormalities in other domains, and more abnormalities that were not identified by PA. Providers were “surprised” by GA results in 33% of cases, mainly with cognitive or social support findings, and reported plans for management change for 39% of patients based on GA findings. Conclusions Including a GA in the care of OA-MBC in CP is beneficial for the detection of multiple abnormalities not detected by routine PA.

TPS4185 Background: Evidence-based data is lacking to guide the care of older adults with newly diagnosed metastatic pancreatic cancer (mPCA). As a result, treatment approach and the selection of chemotherapy regimens are often extrapolated from data from younger patients. Furthermore, vulnerable older adults are often treated with dose adjusted regimens with limited data to support this practice. EA2186 is a phase II randomized controlled trial, and the first prospective study aiming to define the optimal treatment approach of vulnerable older adults with newly diagnosed mPCA. Methods: Patients aged 70 years and over with histologically confirmed pancreatic adenocarcinoma, evidence of metastatic disease, ECOG PS 0-2 and adequate organ function, who are considered vulnerable are eligible for this trial (accrual target 184). This study utilizes a screening geriatric assessment which characterize patients as fit, vulnerable or frail by evaluating functional status, cognition and co-morbidities. Vulnerable patients according to this screening assessment are those with mild abnormalities in functional status, comorbidities and/or cognition, or older than 80 years of age. Those patients will be randomized to receive either modified Gemcitabine/Nab-Paclitaxel or dose-reduced 5-Fluorouracil Leucovorin and Liposomal Irinotecan every 2 weeks. A comprehensive geriatric assessment (GA) and quality of life (QOL) evaluation are completed prior to initiation of therapy for all randomized patients. Follow up will continue until disease progression or withdrawal, with repeated GA and QOL assessments at each disease evaluation. Overall survival is the primary objective, with secondary objectives including progression free survival, and response rate. Enrolled patients will be stratified by age 70-74 vs ≥75, and ECOG PS 0-1 vs 2. Additional endpoints of interest for older adults include: evaluation of risk factors identified through GA, and capturing toxicities of interest for this patient population (i.e. hospitalization, deterioration in PS, and falls). Correlative studies include assessment of pro-inflammatory biomarkers or aging in the blood (IL-6 and CRP) as well as imaging evaluation of sarcopenia and body composition as predictors of treatment tolerance. Clinical trial information: NCT04233866.

INTRODUCTION: Positive cytology from peritoneal washings obtained prior to potential resection of pancreatic cancer is associated with grim prognosis, equivalent to M1 disease. We examine our experience with pancreatic cancer patients who underwent pre-resection lavage in an attempt to predict who would have malignant cells on peritoneal cytology. METHODS: We conducted a retrospective review of patients undergoing pancreatectomy for pancreatic adenocarcinoma at a tertiary care institution from 1995–2019 and had pre-resection lavage performed. Demographic and clinicopathologic data were collected. Logistic regression models were used to identify predictors of positive cytology. RESULTS: Three hundred ninety-nine patients underwent pancreatic resection and had lavage performed. Forty-three (10.8%) had positive peritoneal cytology. Those with positive cytology had higher median Ca19–9 value than those with negative cytology at diagnosis (368.5 vs 200 U/mL, p=0.007) and after neoadjuvant therapy (100.3 vs 43 U/mL, p=0.013). After controlling for preoperative therapy received, an initial Ca19–9 greater than 1220 U/mL (OR 2.72, 95% CI 1.07–6.89, p=0.035), locally advanced disease (OR 4.86, 95% CI 1.31–18.09, p=0.018), and BMI >25 kg/m(2) (OR 2.67, 95% CI 1.04–6.97, p=0.042) were associated with positive cytology in multivariate logistic regression model. The associated ROC curve had an AUC of 0.7507, suggesting adequate discrimination of those with positive peritoneal cytology. CONCLUSION: Diagnostic laparoscopy remains an important adjunct to the workup, diagnosis, and staging of pancreatic adenocarcinoma. Patients with locally advanced disease, significantly elevated serum Ca19–9 at diagnosis, and BMI >25 kg/m(2) may be at higher risk for positive peritoneal cytology, regardless of whether neoadjuvant therapy is administered.

BACKGROUND: Pancreatic adenocarcinoma (PCA) incidence is higher in Black compared to White patients. Beyond race, neighborhood socioeconomic status (nSES) may also inform disparities. However, these effects on metastatic pancreatic adenocarcinoma (mPCA) are not well-studied. The aim of this study was to explore whether nSES influences survival in patients with mPCA. METHODS: nSES measures were derived from U.S. census data at the census tract (CT) level. We correlated medical records of mPCA patients (diagnosed 2010-2016; n=370) to nSES measures retrospectively via a geocode derived from patient address. Multivariable cox proportional hazards models were used to identify patient-level (age, sex, race, marital status, treatment (radiation/chemo/surgery), PCA family history, stage, Jewish ancestry, tobacco use, BMI, diabetes, and statin use) and nSES measures (deprivation, racial concentration, stability, transportation access, immigration) associated with mPCA survival; P values

Many studies show significantly improved survival after R0 resection compared with R1 resection in pancreatic adenocarcinoma (PAC); however, the effect of neoadjuvant chemoradiation (NACRT) on this association is unknown. The aim of this study was to evaluate the prognostic significance of positive surgical margins (SMs) after NACRT compared with upfront surgery + adjuvant therapy in PAC. All cases of surgically resected PAC at a single institution were reviewed from 1996 to 2014; patients treated with palliative intent, metastatic disease, and biliary/ampullary tumors were excluded. The primary endpoint was overall survival (OS). Overall, 300 patients were included; 134 patients received NACRT with concurrent 5-fluorouracil or gemcitabine followed by surgery, and 166 patients received upfront surgery (+ adjuvant chemotherapy in 72% of patients and RT in 65%); 31% of both groups had a positive SM (+SM). The median OS for patients with a +SM or negative SM (−SM) was 26.6 and 31.6 months, respectively for NACRT, and 12.0 and 24.5 months, respectively, for upfront surgery. OS was significantly improved with −SM compared with +SM in both groups (p = 0.006). When resection yielded +SM, NACRT patients had improved OS compared with upfront surgery patients (p

Purpose: The recombinant fusion protein ipafricept blocks Wnt signaling, and in combination with gemcitabine and nab-paclitaxel caused tumor regression in xenografts. This phase Ib study evaluated the combination of ipafricept with nab-paclitaxel + gemcitabine in patients with untreated metastatic pancreatic adenocarcinoma (mPDAC). Patients and Methods: Dose escalation started with standard dose nab-paclitaxel + gemcitabine and ipafricept (3.5 mg/kg days 1, 15). Because of fragility fractures seen with different anti-Wnt agents, following cohorts had ≥6 patients treated with ipafricept 3 to 5 mg/kg on day 1, and included bone marker monitoring and prophylactic bisphosphonates as indicated. On the basis of preclinical data, sequential dosing was evaluated in cohort 4 (ipafricept day 1 followed nab-paclitaxel + gemcitabine day 3). Objectives included safety, MTD, recommended phase II dose, pharmacokinetics, immunogenicity, pharmacodynamics, and efficacy. Results: A total of 26 patients were enrolled, five in cohort 1 and seven each in cohorts 2–4. ipafricept-related adverse events (AEs) of any grade included fatigue, nausea, vomiting, anorexia, and pyrexia. ipafricept-related AEs grade ≥3 included two events of aspartate aminotransferase elevation, and one each of nausea, rash, vomiting, and leucopenia. No dose-limiting toxicities or fragility fractures were observed. Nine patients (34.6%) had partial response, 12 (46.2%) stable disease as best response, with clinical benefit rate of 81%. Median progression-free survival was 5.9 m [95% confidence interval (CI), 3.4–18.4], median overall survival was 9.7 m (95% CI, 7.0–14). The study was terminated by the sponsor due to bone-related toxicity within this therapeutic program and concerns for commercial viability. One patient remains on therapy under compassionate use. Conclusions: Ipafricept can be administered with nab-paclitaxel + gemcitabine with reasonable tolerance. Wnt pathway remains a therapeutic target of interest in mPDAC.

544 Background: Patients with metastatic pancreatic cancer (mPC) have a 5-year survival of 2.7%. Studies have shown that patients with mPC receive aggressive end of life (EOL) care which has been associated with worse quality of life for patients and high use of resources when they are least likely to benefit patients. Methods: A retrospective database of patients with mPC treated at Fox Chase Cancer Center between 2010 and 2019 was analyzed for utilization of palliative care and EOL care. Statistical analysis was performed using one-sample Z tests calculated in Excel. Results: We identified 610 patients with mPC, of whom 39% received palliative care, 56% were referred to hospice, and 91.8% are deceased. The average time from mPC diagnosis to palliative care consult was 232 days, the average time from palliative care consult to death was 121 days. Patients who received palliative care were less likely to receive chemotherapy within 14 days of death (7.7% vs 13.3%, p =0.05), more likely to have a DNR code status (83.3% vs 44.5%, p < 0.0001), and more likely to be referred to hospice (83.9% vs 35.9%, p < 0.0001). The average length of time on hospice was 24 days with no difference between those who received palliative care and those who did not. Patients who were referred to hospice were also less likely to receive chemotherapy within 14 days of death (6.7% vs 19.8%, p < 0.0001). Conclusions: Patients with mPC who had a palliative care team involved in their care were significantly less likely to receive aggressive EOL care.

Background: Prior studies have supported an inverse association between physical activity and colon cancer risk and suggest that higher physical activity may also improve cancer survival. Among participants in a phase III adjuvant trial for stage III colon cancer, we assessed the association of physical activity around the time of cancer diagnosis with subsequent outcomes. Methods: Before treatment arm randomization (FOLFOX or FOLFOX + cetuximab), study participants completed a questionnaire including items regarding usual daily activity level and frequency of participation in recreational physical activity (N = 1,992). Using multivariable Cox models, we calculated HRs for associations of aspects of physical activity with disease-free (DFS) and overall survival (OS). Results: Over follow-up, 505 participants died and 541 experienced a recurrence. Overall, 75% of participants reported recreational physical activity at least several times a month; for participants who reported physical activity at least that often (vs. once a month or less), the HRs for DFS and OS were 0.82 [95% confidence interval (CI), 0.69–0.99] and 0.76 (95% CI, 0.63–0.93), respectively. There was no evidence of material effect modification in these associations by patient or tumor attributes, except that physical activity was more strongly inversely associated with OS in patients with stage T3 versus T4 tumors (Pinteraction = 0.03). Conclusions: These findings suggest that higher physical activity around the time of colon cancer diagnosis may be associated with more favorable colon cancer outcomes. Impact: Our findings support further research on whether colon cancer survival may be enhanced by physical activity. Cancer Epidemiol Biomarkers Prev; 27(6); 696–703. ©2018 AACR.

INTRODUCTION: Oncogenic FGFR2 alterations (fusions/rearrangements, amplifications, mutations) are key drivers in cholangiocarcinoma (CCA) and multiple solid tumors. Current pan-FGFR inhibitor (FGFRi) therapy is limited by off-isoform toxicity and acquired FGFR2 kinase domain resistance mutations. RLY-4008 is a highly selective and potent oral inhibitor designed to target both FGFR2 driver and resistance mutations. We initiated a first-in-human study in advanced solid tumors patients (pts) to define the safety, pharmacokinetics (PK) and efficacy of RLY-4008 (NCT04526106). METHODS: Adult pts received RLY-4008 QD or BID on a 4-week cycle following a BOIN escalation design. Adverse events (AEs), PK, ctDNA and anti-tumor activity (RECIST 1.1) were assessed. RESULTS: As of 16AUG21, 45 pts (35 CCA; 10 other) have been treated with RLY-4008 at total daily doses of 30-200 mg (18 pts BID; 27 pts QD). 44 pts had oncogenic FGFR2 alterations (26 fusions/13 mutations/5 amplifications). The median number of prior anti-neoplastic therapies was 3 (range 1-15). 94% (33/35) of CCA pts had prior chemotherapy and 69% (24/35) had prior FGFRi. 56% (9/16) CCA pts with prior FGFRi and evaluable ctDNA had ≥1 FGFR2 resistance mutation at baseline, most commonly at positions 549 (8/9), 617 (3/9), or 564 (2/9). RLY-4008 had rapid absorption (Tmax 1-7h), half-life to support QD dosing (18-34 h), dose-dependent exposure (AUC; Cmax) and predicted FGFR2 occupancy >85% across dose levels. The MTD has not been defined, and QD dose exploration continues to select the optimal biologically efficacious dose. AEs occurring in >20% of pts include stomatitis (49%), palmar-plantar erythrodysesthesia (PPE, 38%), dry mouth (29%), and nail toxicities (22%), majority of which were ≤Gr 2. 6 pts had Gr 1-2 retinopathy, which resolved in all cases. 5 AEs were considered dose limiting toxicities: 4 in BID (rash/PPE/mucositis/hyperbilirubinemia) and 1 in QD (retinopathy). No Gr 4/5 drug-related AEs were seen. 25 pts remain on treatment (range 1-37 weeks). RLY-4008 showed broad anti-tumor activity across dose levels and FGFR2 alterations with radiographic tumor reductions of ≥10% in 59% pts (19/32; -11% to -83%). Activity was seen in FGFRi-naïve, FGFR2-fusion+ CCA with PRs in 50% of pts (3/6, 2 confirmed and 1 pending confirmation; -56% to -83%). Activity was also seen in FGFRi pre-treated FGFR2-fusion+ CCA pts (N=16) with 16 SD, including 9 pts with tumor reduction ≥10% (from -12% to -35%). Of the FGFRi pre-treated FGFR2-fusion+ CCA patients with detectable FGFR2 resistance mutations in ctDNA at baseline, 78% (7/9) were undetectable at C2D1. CONCLUSION: RLY-4008 demonstrates promising safety, tolerability, and clinical activity in FGFR2-altered solid tumor pts, including those who progressed on prior FGFRi therapy. Consistent with the FGFR2-selective mechanism, minimal off-isoform toxicity (FGFR1-hyperphosphatemia; FGFR4-diarrhea) was seen. These encouraging data validate selective targeting of FGFR2 and suggest that RLY-4008 has potential to overcome resistance to FGFRi. Citation Format: Lipika Goyal, Mitesh Borad, Vivek Subbiah, Amit Mahipal, Suneel Kamath, Kabir Mody, Robin Katie Kelley, Richard Kim, Vaibhav Sahai, Anthony El-Khoueiry, Efrat Dotan, Oleg Schmidt-Kittler, Jinshan Shen, Kai Yu Jen, Alicia Deary, Wei Guo, Mahesh Padval, Cori Ann J. Sherwin, Charles Ferte, Beni Wolf, Alison M. Schram. First results of RLY-4008, a potent and highly selective FGFR2 inhibitor in a first-in-human study in patients with FGFR2-altered cholangiocarcinoma and multiple solid tumors [abstract]. In: Proceedings of the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; 2021 Oct 7-10. Philadelphia (PA): AACR; Mol Cancer Ther 2021;20(12 Suppl):Abstract nr P02-02.

Purpose/objective(s) The mainstay of treatment for unresectable/inoperable biliary cancers (UIBC) is chemotherapy (CHT) and radiotherapy (RT). We report our single institution clinical efficacy and safety in patients with UIBC treated with SBRT versus conventionally fractionated radiation (CRT). Materials/methods Patients with UIBC treated with SBRT (n = 18) or CRT (n = 23) between 2006 and 2020 were identified. Additional management included neoadjuvant, adjuvant and/or concurrent CHT. Kaplan-Meier estimates of progression free survival (PFS), overall survival (OS) and locoregional control (LRC) were compared with log rank tests. Toxicities during treatment and follow up were based on the CTCAE v5.0. Acute toxicity was defined as adverse events Results Of the 41 patients analyzed 54% were male, and 20% were non-white. CRT patients were younger than SBRT (median age 64 vs 76 yrs., P 5 cm tumors in the SBRT (51%) group than CRT (22%). The median SBRT dose was 60 Gy in 5 fractions and the median dose for CRT was 50 Gy in 25 fractions. SBRT dose was dichotomized into BED10 ≥ 100 Gy and 5 cm (P = 0.097). For acute toxicity, both treatments were well tolerated overall with only 1 patient with grade 3+ toxicity. 74% of CRT patients had an acute toxicity compared to 39% of SBRT patients (P = 0.024). There was no difference in late toxicity between the two groups. There was no grade 3+ late toxicity. Conclusion In this single-institution retrospective study, there was improved PFS in UIBC treated with SBRT. There was a trend towards improved LRC in larger tumors. Dose escalation to BED10 ≥ 100 Gy in this series improved OS. SBRT was also better tolerated than CRT.

236 Background: Older adults are more likely to be diagnosed with cancer than their younger counterparts. Because the underlying health status of older adults with cancer is generally heterogeneous, geriatric assessment (GA) is helpful for uncovering age-related vulnerabilities and guiding subsequent care planning. GA provides multidimensional, multidisciplinary evaluations of pertinent health domains. When used to evaluate an older adult with cancer prior to initiating therapy, GA and screening tools can help oncologists differentiate between fit and frail patients and tailor their treatment accordingly. Methods: The Association of Community Cancer Centers (ACCC) conducted a 4-round Delphi method to achieve expert consensus (≥75%) related to 9 domains of geriatric oncology care from a multidisciplinary perspective. A survey was conducted with 70 international clinicians working in geriatric oncology to assess perspectives on guideline-recommended GA tools in clinical practice. Facilitator led focus groups were conducted to review the results in a large group format and come to consensus. Aggregated results were shared back with the group to ensure effective capture of group discussion regarding validated clinical practice tools to include as resources in the gap assessment instrument. Results: A 32 question geriatric oncology gap assessment was developed in an online survey platform. This tool was beta tested by 30 individuals at cancer programs of various types and regions across the US. A final version was published and made accessible for multidisciplinary teams to self-assess care delivery for older adults with cancer in 9 domains: Functional Status; Cognition; Comorbidities; Decision Making: Screening, Life Expectancy, Chemo Toxicity; Pharmacy/Medication Management; Psychological Health; Nutrition; Patient Goals and Needs; and Communication and Workforce Training. Within each domain, respondents select the level (see Table) that most closely represents the practice(s) at their institution. A personalized report is generated. Sample Question. Conclusions: The ACCC geriatric oncology gap assessment offers cancer programs a validated way to evaluate care delivery for older adults with cancer. To optimize workflow, cancer programs should consider utilizing gap assessment results to develop and advance scalable quality improvement programs at their institution, taking into consideration resource level and infrastructure.[Table: see text]

Given the prevalence and the rising incidence of hepatocellular carcinoma (HCC) in older adults worldwide, there is an urgent need to improve our understanding of the implications of treatment modalities in this population. The care of older patients with HCC is challenging due to the lack of evidence-based recommendations in this population. The current treatment approach for older patients relies on extrapolation of data from clinical trials conducted mostly in younger patients or fit older adults. Further, in the last few years, the arsenal of systemic treatments has increased with currently seven FDA-approved therapies available for patients with advanced HCC. Therefore, understanding how to apply current data to this unique and diverse patient population is necessary. This review will aim to shed light on the approach to older adults with HCC through an assessment of available data in the literature.

Background Nutritional status can directly affect morbidity and mortality in older adults with cancer. This study evaluated the association between pretreatment body mass index (BMI), albumin level, and unintentional weight loss (UWL) in the prior 6 months and chemotherapy toxicity among older adults with solid tumors. Methods This was a secondary analysis of a prospective, multicenter study involving chemotherapy-treated patients 65 years old or older. Geriatric assessment, BMI, albumin level, and UWL data were collected before treatment. Multivariable logistic regression models evaluated the associations between nutritional factors and the risk of grade 3 or higher (grade 3+) chemotherapy toxicity. Results Seven hundred fifty patients with a median age of 72 years (range, 65-94 years) and mostly stage IV disease were enrolled. The median pretreatment BMI and albumin values were 26 kg/m2 (range, 15.1-52.1 kg/m2 ) and 3.9 mg/dL (range, 1.0-5.0 mg/dL), respectively. Nearly 50% of the patients reported UWL, with 17.6% reporting >10% UWL. Multivariable analysis revealed no association between >10% UWL and a risk for grade 3+ chemotherapy toxicity (adjusted odds ratio [AOR], 0.87; P = .58). Multivariable analysis showed a trend toward an association between a BMI ≥ 30 kg/m2 and a decreased risk of grade 3+ chemotherapy toxicity (AOR, 0.65; P = .06), whereas a low albumin level (≤3.6 mg/dL) was associated with a higher risk of grade 3+ chemotherapy toxicity (AOR, 1.50; P = .03). An analysis of the joint effect of BMI and albumin demonstrated the lowest risk of grade 3+ chemotherapy toxicity among patients with high BMIs (≥30 kg/m2 ) and normal albumin levels (AOR, 0.41; P = .008). Conclusions Among older adults with solid tumors, higher BMIs and normal albumin levels are associated with a lower risk of grade 3+ chemotherapy toxicity. Additional research is warranted to define the clinical significance of nutritional markers and to inform future interventions.

1528 Background: The COVID-19 pandemic has disrupted US healthcare delivery and led to delays in life-prolonging therapy for some conditions. Its impact on diagnosis and timely care delivery for patients (pts) with cancer is unknown. We assessed the pandemic’s impact on time from advanced diagnosis to systemic treatment initiation (TTI) for pts with newly diagnosed advanced solid cancers. Methods: We performed a controlled interrupted time series analysis using the nationwide Flatiron Health electronic health record-derived de-identified database, which originated from ̃280 US cancer clinics. The study sample included pts ≥ 18 years diagnosed with advanced solid cancers from Jan 1-Jul 31 in 2019 or in 2020, excluding a 30-day period (Mar 8-Apr 7) encompassing the start of most state stay-at-home orders. We used Cox proportional hazards models to estimate standardized predicted probabilities of TTI within 30 days of advanced diagnosis before (Jan-Mar) and during (Apr-Jul) the pandemic in 2020, compared to historical controls in 2019, adjusted for age, sex, race, insurance, performance status, and cancer type. Interactions by cancer type and race examined heterogeneity of effects. Results: The study included 12,977 pts (median age 69 yrs [IQR 61-77]; 47.4% female; 59.4% non-Hispanic white). At the time of analysis, fewer advanced cancer diagnoses were recorded in 2020 (Jan-Mar 2,409; Apr-Jul 3,027) than in 2019 (Jan-Mar 2,910; Apr-Jul 4,631). Compared to Apr-Jul 2019, pts diagnosed with advanced cancer during the COVID-19 period were more likely to have de novo (vs recurrent) disease (67.3% vs 56.8%). In adjusted models, the COVID-19 period was associated with an increased probability of treatment within 30 days (adjusted difference-in-differences +5.2 percentage points [ppts]). TTI improvements were not observed for pts with advanced breast cancer or Black pts, but effect differences across subgroups were not statistically significant (Table). Conclusions: Among pts diagnosed with advanced cancer, the COVID-19 pandemic was associated with shorter time to systemic therapy initiation. These treatment patterns may reflect the fewer advanced cancer diagnoses and higher proportion of de novo cancers observed during this period. Longer follow-up and data maturity are needed to understand the impact of the pandemic on clinical outcomes.[Table: see text]

4086 Background: Pemigatinib (PEMI), a potent, selective, oral FGFR1-3 inhibitor, has shown efficacy and safety in patients (pts) with CCA and FGFR2 rearrangements/fusions in FIGHT-202 (NCT02924376; objective response rate [ORR], 35.5%; duration of response [DOR], 7.2 months [mo]). Overall survival (OS: 21.1 mo) was not mature in the primary report (Abou-Alfa. Lancet Oncol 2020; cutoff: Mar 22, 2019); herein we report matured efficacy and safety data from FIGHT-202 (cutoff: Apr 7, 2020). Methods: Pts (≥18 y) with known FGF/FGFR alterations and progression after ≥1 prior therapy had FGFR2 rearrangements/fusions (cohort A), other FGF/FGFR alterations (B), or no FGF/FGFR alterations (C). Pts received PEMI 13.5 mg QD (21-d cycle; 2 wks on, 1 wk off) until progression or toxicity. Primary endpoint: independent, centrally confirmed ORR (cohort A); secondary endpoints: ORR (cohorts B, C; cohorts A and B combined); DOR, disease control rate (DCR), progression free survival (PFS), OS, and safety. A post-hoc analysis in cohort A evaluated mOS in responders (pts with complete response [CR] or partial response [PR]) vs non-responders (pts with progressive disease [PD] or stable disease (SD]). Results: At cutoff, 147 pts were enrolled (cohort A, n=108; B, n=20; C, n=17; FGF/FGFR status undetermined, n=2); median follow-up was 30.4 (range, 4.9–38.7) mo and median treatment duration was 5.9 (0.2–36.5) mo. In cohort A, 9.3% of pts remained on therapy at cutoff; in cohorts B and C, all pts had discontinued. Pts discontinued mainly for PD (67.6%, 75%, and 64.7% in cohorts A, B, and C respectively). Independent, centrally confirmed ORR was 37.0%; mOS was 17.5 mo (95% CI, 14.4-22.9) in cohort A (Table 1). mOS for responders (n=40) vs non-responders (n=68) was 30.1 (95% CI, 21.5-NE) mo vs 13.7 (9.6-16.1) mo. Overall, most common all-cause treatment-emergent adverse events (TEAEs) were hyperphosphatemia (58.5%; grade ≥3, 0%), alopecia (49.7%; 0%), diarrhea (46.9%; 3.4%), fatigue (43.5%; 5.4%), nausea (41.5%; 2%), and dysgeusia (40.8%; 0%); 10.2%, 13.6% and 42.2% of pts discontinued, had dose reduction, and treatment interruption due to TEAEs, respectively. Conclusions: These results reinforce the primary data, showing continued, durable responses and sustained tolerability in pts receiving PEMI for CCA harboring FGFR2 rearrangements/fusions. Notably, the matured OS is longer than historical data; OS for responders was more than twice as long vs for non-responders. Clinical trial information: NCT02924376. [Table: see text]

e13063 Background: The median age at diagnosis of breast cancer is 62 with 45% of patients over the age of 65. At diagnosis, up to 5% of patients will have metastatic breast cancer (MBC) and up to 30% of patients with early-stage disease will develop MBC. There are no clear guidelines on how to treat older adults with MBC (OA-MBC) due to their poor representation in clinical trials. This lack of recommendations can often lead to under treatment of OA-MBC. This study evaluated the self-reported treatment patterns of practitioners in community practices for OA-MBC and evaluated the actual treatment their OA-MBC patients received. Methods: This is a secondary analysis of a multi-phase trial which initially evaluated the gaps in practice patterns that exist in the assessment and management of OA-MBC and did a prospective comparison between the older patient’s geriatric assessment and provider’s clinical assessment. In this analysis we focused on the practice patterns in the community. Physicians completed questionnaires detailing their front-line treatment choices for each subcategory of MBC in women over the age of 65. Data was then collected on patients in these physicians’ practices including their current line of treatment, treatment regimen, comorbidities, performance status and demographics. The appropriateness of treatment choice was then evaluated based on MBC subcategory and line of treatment using the NCCN guidelines for breast cancer. Patient and physician characteristics and treatment choices were summarized using descriptive statistics. Results: 44 providers from 9 community practices located in PA, DE, NJ, MT, and WA participated. Majority of providers were Caucasian (57%) and had been in practice for >11 years (53%). 100 patients were evaluated from these practices between December 2016 – April 2019. Median age 73 (65-90). In response to front-line therapy choices, 27/44 (61%) providers selected endocrine only therapy for HR+ but in practice, 29/37 (78%) of HR+ patients were treated with combination endocrine & CDK 4/6 inhibitors. For HER2+, 20/44 (45%) providers selected trastuzumab + chemotherapy for front-line therapy and in practice 8/8 (100%) of patients received this combination. For TNBC, 37/44 (84%) providers agreed with sequential single agent chemotherapy over combination and in practice 6/7 (86%) patients received this. Including all lines of therapy, 84/100 patients were treated in accordance with NCCN guidelines. Conclusions: Despite the lack of older adult guidelines, our community-based practitioners are treating the majority of their OA-MBC patients appropriately and in accordance with NCCN guidelines. In our cohort of OA-MBC there was no evidence of under treatment, however, due to the lack of sufficient data in this patient population it is not clear that this approach is beneficial. Additional research is needed to refine the treatment approach of this unique patient population.