Avera Cancer Institute Research Articles

Characterization of social determinants of health in patients considered for participation in treatment clinical trials at a community cancer center serving the Great Plains.

e13704 Background: Avera Cancer Institute, a community-based cancer network comprised of six rural cancer centers in SD and MN, provides care to a five-state region in the upper mid-west covering 72,000 square miles and offers several clinical trials to patients to offer access to advanced treatment for malignancies. Malignances are known to disproportionally affect patients that are older, rural, minorities, and have lower socioeconomic status, which are all less likely to enroll into clinical trials. Methods: Patients evaluated for participation in clinical trials from 2018-2022 were identified in an institutional database. Trial type was designated as either a treatment or nontreatment trial. Status of trial involvement was designated between enrolled or screened. Their demographic information was obtained from the electronic health record (EHR). Demographic information obtained from the EHR includes race, ethnicity, language spoken, gender, employment status, insurance type, and if they live in an urban or rural area as defined by the US Census Bureau. Clinical trial portfolio during this time includes trials for breast, gynecological, gastrointestinal, lung, and hematologic malignancies. Results: 4,397 patients were considered for participation in a clinical trial at our institution in the studied timeframe. Of these patients, 1887 were screened for treatment trials and of that group, 773 were enrolled. 35% of participants considered for clinical trials were from urban areas while 65% considered were rural. 48% of the urban population ultimately were enrolled on a clinical trial while 44% of rural population participated. Participants who lived in an urban area 25-50 miles from our study site had an enrollment rate of 49% compared to rural enrollment of 33%, from 50-100 miles rates of 53% and 37%, from 100-250 miles rates of 29% and 41%, and from greater than 250 miles rates of 44% and 33%, respectively. 99.5% of the population was non-Hispanic, 97% were White, and 99% were English speaking. 74% of the total population were female and 26% were male. Females had an enrollment rate of 51% while males had an enrollment of 29%. Patients with no insurance enrolled in trial 62% compared to 36% of those with commercial insurance The average national Area Deprivation Index percentile for screened patients was 57 vs 59 for enrolled patients. Conclusions: This retrospective study demonstrates a greater likelihood for females, urban patients, and white, English-speaking patients to enroll into clinical trials. Our data also demonstrate a preference for uninsured patients to enroll into clinical trials, possibly due to the financial benefits they may provide. Further directions include comparing our patients considered for clinical trials to all patients treated at our institution to identify potential disparities in care.

Utilization of genetic and genomic data and correlation to outcomes of treatment with PARP inhibitors in advanced or metastatic castrate-resistant prostate cancer.

e17034 Background: Prostate cancer is the second-leading cause of cancer death in men in the United States, with aggressive forms associated with mutations in homologous recombination repair (HRRm) genes. PARP inhibitors (PARPi) (olaparib, rucaparib, niraparib, and talazoparib) are FDA approved for treatment of HRRm metastatic castration-resistant prostate cancer (mCRPC). Previous data have shown PARPi has the greatest benefit in patients with HRRm, but the responses in HRR genes other than BRCA1/2 and ATM are less robust based on available data. Methods: This retrospective study utilized the electronic health record to identify adult patients diagnosed with prostate cancer and treated at Avera Cancer Institute from 1/1/2018 to 12/31/2022 who received somatic (tumor and/or ctDNA) and/or germline genetic testing. Testing results were reviewed for pathogenic HRRm (BRCA1, BRCA2, ATM, ATR, CDK12, CHEK2, FANCA, MLH1, MRE11A, NBN, PALB2, or RAD51C) and treatment histories were reviewed to identify PARPi use. Data about PARPi received, duration, and biochemical response (decline in PSA during therapy) were collected. Results: 191 patients were included in the final analysis. Of these, 88 (46%) patients had germline only testing, 31 (16%) had somatic only testing, and 72 (38%) had both germline and somatic testing completed. 45 patients had HRRm of which 22 were somatic and 33 were germline. The average patient age at time of testing was 70 years. Thirteen of the patients in this cohort received treatment with a PARPi . Twelve of these patients received treatment with olaparib monotherapy, and one patient received olaparib in combination with abiraterone. Average progression free survival was 26 months (range 5-92 months) and the median PFS was 11 months. Four patients were biochemical non-responders, with an average PFS of 8 months, compared to 33 months for the 9 biochemical responders (p=0.04). Gene alterations present in non-responders included germline BRCA1 (n=1), germline CHEK2 (n=2), and somatic ATM (n=1). Germline alterations present in responders included BRCA2 (n=7) and PALB2 (n=2). In patients who received PARPi therapy, the average age of testing was 73 years. Conclusions: The patients found to have HRRm that were treated with a PARPi showed similar responses to previously described data in that the BRCA2 mutated group showed best response, followed by PALB2 mutated tumors. The overall proportion of patients with HRRm that were ultimately treated with PARPi was smaller than expected warranting further investigation. New FDA approvals of PARPi combined with next generation hormonal agents in the first line mCRPC setting are expected to increase utilization of PARPi. Additional outcomes data for individual HRR genes are needed to improve patient selection, outcomes, and reduce unnecessary toxicity due to PARPi therapy.

Total neoadjuvant therapy for rectal cancer in the rural community oncology setting.

41 Background: The treatment of localized rectal adenocarcinomas with Total Neoadjuvant Therapy (TNT) has become the national standard. Data on the efficacy of TNT in a predominantly rural community oncology setting is limited. Methods: This ongoing retrospective analysis included 94 patients with proficient MMR Stage II or III rectal adenocarcinoma treated with traditional neoadjuvant treatment of chemoradiation followed by surgical resection +/- adjuvant chemotherapy, or Consolidation (chemoradiation upfront) TNT versus Induction (chemotherapy upfront) TNT followed by surgical resection, diagnosed between 2017 and 2022 and treated at the Avera Cancer Institute in Sioux Falls, South Dakota. The primary objectives were to compare the pathologic response and treatment completion rates in patients with rectal cancer treated with TNT to patients treated with traditional neoadjuvant treatment. The secondary objective was to compare the pathologic response rate for TNT at different tumor locations. Results: Of 94 patients assessed, 54 patients received traditional neoadjuvant treatment and 40 patients received TNT. For patients treated with traditional neoadjuvant treatment, 43% (n=23) completed all recommended treatment, with 63% (n=34) achieving a partial response (PR) and 19% (n=10) a complete pathologic response (CR). For patients treated with TNT, 93% (n=37) completed all recommended treatment, and 68% (n=27) achieved a PR and 15% (n=6) achieved a CR. For patients that received Consolidation TNT (n=21), 66% (n=12) achieved a PR and 21% (n=4) achieved a CR. For patients that received Induction TNT (n=19), 68% (n=13) achieved a PR and 11% (n=2) achieved a CR. For patients with high tumor location (n=4) treated with TNT, 50% (n=2) achieved a PR and one patient achieved a CR (25%). For patients with mid tumor location (n=18) treated with TNT, 67% (n=12) achieved a PR and 22% (n=4) achieved a CR. For patients with low tumor location (n=18) treated with TNT, 72% (n=13) achieved a PR and one patient (6%) achieved a CR. Conclusions: The treatment of rectal adenocarcinoma with TNT in the rural community cancer center setting is achievable with a higher completion rate compared to traditional neoadjuvant treatment. Our results also show a trend toward a higher complete pathologic response rate in Consolidation compared to Induction approach and in high/mid rectal tumors compared to low rectal tumors. Future work will be conducted to assess for any differences in recurrence and survival.

Evaluating the impact of a molecular tumor board in a community oncology center: Results from the Avera Cancer Institute's experience.

e13500 Background: The use of molecular tumor boards (MTB) has been widely documented at large academic medical centers, but there is limited experience and data available in smaller settings like community oncology centers. The Avera Cancer Institute has had a molecular tumor board in place since 2014, but the composition and methodology have changed over time. Our 10 years of hands-on experience and involvement in studies like I-PREDICT showed that in addition to molecular matching, considering factors like tumor type, previous treatment responses, comorbidities, medication coverage, and treatment availability provide crucial insights for determining optimal therapy for patients. Methods: We analyzed next-generation sequencing (NGS) testing results from August 2019 to December 2022. At the time of NGS testing result, providers were offered to have the case reviewed and presented at MTB. Our multidisciplinary team consists of members with backgrounds in bioinformatics, medical oncology, pathology, translational science, trial coordination, and pharmacy. Recommendations from the MTB discussions were provided in three categories: standard of care, clinical trials, and off-label options. Results: From August 2019 to December 2022, 1,514 qualified or resulted NGS reports were returned and considered for analysis. 733 (48%) were presented at the molecular tumor board and from this group, 629 patients were evaluable. Oncologists chose a recommended therapy 66% of the time. Of the remaining 34%, the most common reason for not utilizing recommendations was that patients were unable to receive further lines of systemic therapy. A subset analysis of 202 cases (June 2021 – August 2022) who either received a recommended therapy (n = 88, 43.6%, group 1) or not (n = 114, 56.4%, group 2) showed a survival benefit. Median overall survival was not reached in group 1, as compared with 14 months in group 2 (HR = 0.58; 95% CI, 0.37 – 0.92; p< 0.02). The median PFS was 8.2 months in group 1 versus 5 months in group 2 (HR, 0.67; 95% CI, 0.48 - 0.92; p< 0.017). Conclusions: The results of our study demonstrate the positive impact of a molecular tumor board review in helping oncologists determine the best treatment options for their patients. Our findings show that recommendations made by the board are well received and frequently adopted by providers. While providers generally prefer standard of care options or clinical trials, they are open to considering all available options to make informed therapy decisions.

54. CancerTrialMatch: A computational resource for the management of clinical trials at a precision oncology center

The routine use of genetic and genomic sequencing in the treatment of cancer has been steadily rising over the past few years, with a corresponding increase in the availability of biomarker-based clinical trials. At the Avera Cancer Institute, biomarker-based clinical trials are often presented as treatment options to oncologists at the molecular tumor board. This necessitated a way to capture structured trial data, and match them to patients based on their disease and sequencing profile in a systematic manner. We developed an open-source web application, CancerTrialMatch, that has the ability to (i) add trials through a semi-automated curation interface, (ii) browse and search trials, (iii) and match patients to biomarker-based trials. This application uses R Shiny to create simple interfaces, a mongo database to store trial data, various R libraries to query data and perform computations, and Docker to manage software installation and application instantiation. The curation interface is semi-automated because querying the clinicaltrials.gov API will return discrete data for many fields, but not for biomarkers or for disease subtypes. The user has to manually input disease type based on the OncoTree classification, as well as biomarker information for mutations, copy numbers, fusions, TMB, MSI/PD-L1 status, RNA expression, and disease-specific markers such as ER/PR/HER2 status. We believe that this application will reduce the person-hours required for trial management for a patient, aid in increasing clinical trial enrollment by systematically providing treatment options, and is thus an important tool in the clinical application of precision oncology.

Abstract 1899: TrialMatch: A computational resource for the management of biomarker-based clinical trials at a precision oncology center

Abstract Introduction: The adoption of routine tumor sequencing, and the incorporation of biomarker-based clinical trials in the treatment of cancer has been steadily rising over the past few years. Access and ability to participate in clinical trials is a key element in providing therapeutic options for cancer patients.At the Avera Cancer Institute, options of biomarker-based clinical trials are routinely presented to the treating clinicians at the molecular tumor board (MTB). With everincreasing numbers of trials, a systematic method for keepingtrack of available trials andevaluating patients for trial options was needed. A search for solutions led to only one open-source tool, MatchMiner, but it did not meet our needs. Methods and Results: We developed an open-source web application, TrialMatch, that has the ability to (i) add trials through a semi-automated curation interface, (ii) browse and search trials, (iii) and match patients to biomarker-based trials.TrialMatch is an R Shiny application that uses a mongo database to store the trial data. Software installation and application instantiation is managed through Docker. Curate This section has fields for a user to enter trial name and a NCT ID from clinicaltrials.gov. It then queries the clinicaltrials.gov API and fetches data about the sponsor, treatment, etc.Although disease and biomarker data are available on clinicaltrials.gov, they are not stored as discrete fields that can be queried, and hence require manual input. The user provides disease type based on the OncoTree classification, as well as biomarker information for mutations, copy numbers, fusions, TMB, MSI status, PD-L1 status, RNA expression, and disease specific markers such as ER/PR/HER2 status.All information for a particular trial is entered in a mongo database collection, with each trial stored as a document. The ability to add and edit data fields can be restricted to specific users. Browse This section allows the user to browse through all trials with key information such as NCT ID, trial name, disease, and biomarkers. Each row represents one trial and can be expanded to show more detailed information. This is useful to keep track of trials, and to quickly filter trials to a specific disease or biomarker. Match This section displays a patient-centric view of the trials that each patients’ age, sex, disease, and biomarkers have matched to. The matching can be automated for scheduled recurrentruns. At Avera, this is used during MTB to evaluate treatment options, but can also be used by clinicians to get a sense of the trials available for their patients, while awaiting formal review. Conclusion: We believe that this computational tool fulfills a crucial need in the clinical application of precision oncology, and will ultimately increase clinical trial enrollment for patients. Citation Format: Anu Amallraja, Shivani Kapadia, Padmadpriya Swaminathan, Casey Williams, Tobias Meissner. TrialMatch: A computational resource for the management of biomarker-based clinical trials at a precision oncology center [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1899.

Abstract 269: PD-L1 dominated tumor-CAF-immune cell crosstalk of stromal microenvironment: Endometrial tumor vs. tumor-adjacent normal

Abstract Background: In endometrial cancers (EC), the mechanistic contribution of PD-L1/L2 and PD-1 signaling of host’s stromal microenvironment (SME) [cancer-associated fibroblast (CAF) and immune cells] in relation to the tumor (T) cells is elusive. Aim: To understand the tumor-stroma-immune crosstalk in EC, we studied the compartmental pattern of PD-L1, PD-L2, and PD-1 expression in EC tissues and their matched CAFs from both T and tumor-adjacent normal (N) tissues. Method: Over 116 surgically resected T and N tissues were obtained from consented patients with EC at the Avera Cancer Institute (March ‘16 and September ’21). IHC expression was performed in T, N-epithelium, SME (mesenchyme) in the T and N tissues. The staining intensity and distribution pattern were evaluated by a pathologist using a standard scoring system (1% cut-off value). Since fibroblasts are the most abundant cells of SME, the PD-L1 was parallelly evaluated in the multiple passages of cultured T and N derived CAFs by the qRT-PCR, flow-cytometry, and ICC. Result: The expression of 3 immune checkpoint proteins in the epithelial and mesenchyme of N was limited to only rare and focal positivity for PD-L1. The epithelial compartments of the T tissue, in contrast, had 70% positivity for PD-L1, which was independent of differentiation status, presence of TILs, or lymphovascular invasion. PD-L1 positivity was 90% of the SME of tested samples, identified predominantly in the (1) immune component, including macrophages and lymphocytes, and (2) EpCAM-/SMA+/FAP+/S100A4+ CAFs. Both PD-L1 and PD-L2 were identified by flow, ICC, and qRT-PCR in NCAF and TCAF. The overall expression of PD-L2 was found to be qualitatively and quantitatively lesser than that of PD-L1, primarily contributed by SME/stromal macrophages and lymphocytes. PD-1 expression was restricted to the SME/stromal immune components, predominantly lymphocytes. The expression for PD-L1 and PD-L2 mRNA was higher in TCAF than NCAF in successive passages, which ICC and flow cytometry confirmed. Summary: The expression of immune checkpoint proteins, PD-L1, and PD-L2, are primarily tumor-driven and associated with the endometrioid (invasive) and serous adenocarcinomas of grades II and above with myometrial invasion. The expression of PD-L1 and PD-L2 are distributed in both tumor and SME/stromal components, while PD-1 expression is exclusively SME/stromal. Citation Format: Xiaoqian Lin, Jennifer Aske, Adam Dale, Nischal Koirala, Ethan Thompson, Mary Fagerness, Natasha Flier, Paige Davies, Stacy Kehoe, Cheryl Ageton, Kris Gaster, Luis Rojas Espaillat, David Starks, Raed Sulaiman, Pradip De, Nandini Dey. PD-L1 dominated tumor-CAF-immune cell crosstalk of stromal microenvironment: Endometrial tumor vs. tumor-adjacent normal [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 269.

Landscape of tumor genetic testing and targeted therapies over an eight-year span in a rural population.

e15036 Background: Advances in tumor molecular profiling and bioinformatics are adding new insights to support real-world research. In this study, paired tumor NGS testing data was curated and analyzed from electronic medical records (EMR) to understand mutational and targeted therapy landscape. Methods: A database initiated in 2013 to collect data, including outcomes, on all patients referred to the molecular tumor board at the Avera Cancer Institute was curated and analyzed. A data pipeline that combined results from curated NGS data with curated EMR data from Avera was used to correlate targetable mutations to a corresponding therapy and assessed treatment patterns. Results: Data were from 1804 patients with 44 cancer types including breast (462; 26%), lung (338;19%), colorectal (198;11%), ovarian (168;9%), and uterine (100;5%). Overall, 83% of patients had a positive NGS result and 67% had a targetable mutation per NCCN guidelines. 32% of patients with a targetable mutation received targeted therapy per guideline. Overall, 381 patients with 28 tumor types received targeted therapies based on NGS results and targetable biomarkers. Of these, 288/381 (76%) were stage III-IV and 93/381 (24%) early stage/stage unknown. In non-small cell lung cancer, 76% of stage III-IV patients with mutations in EGFR (exon 19 deletion, L858, L861, S768, G719), MET (exon 14 skipping, amplification), BRAF V600 and ALK/ ROS1/ RET fusions received a targeted therapy per NCCN guidelines. In advanced breast cancer, 97% with ERBB2 amplification received targeted therapy (trastuzumab, pertuzumab, neratinib, lapatinib, tucatinib). 8% of advanced breast cancer patients with PIK3CA mutation received alpelisib, with all patients receiving the drug since 2019. 38% advanced breast cancer patients with BRCA1/2 mutation received Olaparib. In ovarian cancer, 48% of advanced stage patients received targeted therapy for BRCA 1/2, ATM, CDK12, CHEK2, ERBB2, FANCL, KRAS, ALK, BRAF alterations. Olaparib was used in 70% of advanced prostate cancer patients with BRCA1/2 mutations. Dabrafenib combined with Trametinib were most preferred for BRAF V600 mutation in melanoma and colorectal tumors respectively. Off label use of targeted therapy was observed in about 6% of advanced patients; examples include trametinib for KRAS/NRAS mutation [non-small cell lung cancer, colorectal, pancreatic, ovarian], PARP inhibitors for BRCA1/2, ATM mutations [urothelial, peritoneal], anti-ERBB2 inhibitors for ERBB2 in-frame, missense, exon 20 insertion mutations [lung and breast]. Conclusions: These study results demonstrate that automated data mining can provide insights into the genomic and therapeutic landscape of a real-world patient population. Across all tumor types, most patients are being given appropriate targeted therapies as per guidelines. Off-label use of targeted therapy was also observed.

Abstract P2-08-20: Risk of everolimus- and alpelisib-induced hyperglycemia in obese and non-obese breast cancer patients with or without pre-existing hyperglycemia

Abstract Purpose:. Breast cancer is a common malignancy among women. About one in eight women in the US will be diagnosed with breast cancer during their lifetime. One of the most commonly altered genetic pathways in breast cancer patients is the PI3K/AKT/mTOR pathway. Among patients treated with everolimus and alpelisib, hyperglycemia is a frequently encountered adverse event. The cause of hyperglycemia is believed to be the inhibition of PI3K/mTOR, which not only plays a role in oncogenesis but also regulates glucose transportation and glycogen synthesis. Inhibition of PI3K/mTOR activity from treatment results in decreased insulin secretion and hyperglycemia. Obesity is a risk factor for both breast cancer and hyperglycemia. Over 70% of breast cancer patients seen in our center are overweight or obese. Being obese alone increases a patient’s risk of developing insulin resistance and hyperglycemia. Little research has been done on whether obese breast cancer patients are at higher risk of treatment induced hyperglycemia. The purpose of this study was to test whether obesity and pre-existing hyperglycemia are risk factors that increase the patients’ chance to develop hyperglycemia while being treated with anti-PI3K/mTOR drugs. Methods:. A retrospective study was performed on 119 breast cancer patients at Avera Cancer Institute. Female patients who had been treated with everolimus and/or alpelisib were included. According to the CDC standard, patients with body mass index (BMI) greater than 25 kg/m2 were considered as obese. Grade 2 and above hyperglycemia was defined as fasting blood glucose level greater than 160 mg/dl per CTCAE. Baseline blood glucose levels prior anti-PI3K/mTOR treatment were considered high if greater than 140 mg/dl per the American Diabetes Association. Results:. Of the 119 patients, 78 were ER+/HER2-; 22 were triple negative; 12 were ER-/HER2+ and 7 were ER+/HER2+. The BMI ranged from 17.79 to 52.87 (94 obese patients). Patients were kept on everolimus/alpelisib from 14 days to 5 years (median = 6 month). After starting everolimus/alpelisib, 17 patients developed hyperglycemia Grade 2 or greater, 16 of whom were obese. Being obese increased the odds of developing hyperglycemia under anti-PI3K/mTOR treatment by 4.58, However, this increase was not significant (p=0.16). Hyperglycemia in most patients was controlled by diet and lifestyle changes. Four patients (all obese) needed either insulin, metformin, DPP-4 and/or SGLT2 inhibitors to control blood glucose levels. Three patients had type 2 diabetes prior to therapy. The fourth patient developed Grade 3 hyperglycemia (>250 mg/dl) nine month after starting everolimus and was put on insulin for two months, with blood glucose returning back to normal. Everolimus was continued for another three month without causing hyperglycemia in this patient. Our data suggests that baseline blood glucose levels play a significant role in developing high grade hyperglycemia under anti-PI3K/mTOR treatment. The odds of developing hyperglycemia increase by a factor of 5.38 in patients with high blood glucose prior treatment (p= 0.007). Conclusion:. Being obese does not alone present a significantly higher risk of developing high grade hyperglycemia while being treated with anti-PI3K/mTOR drugs compared to non-obese patients if their blood glucose is well controlled. Most patients can manage their blood glucose level by diet and lifestyle changes. Patients starting anti-PI3K/mTOR treatment with high blood glucose level at baseline are at a much higher risk of developing drug-induced hyperglycemia and should be closely monitored. Citation Format: Bing Xu, Tobias Messiner, Casey Williams. Risk of everolimus- and alpelisib-induced hyperglycemia in obese and non-obese breast cancer patients with or without pre-existing hyperglycemia [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P2-08-20.

Abstract PD3-02: Linking proliferative signal to DNA-damage signal in a tumor cell: A contextual synergy between the PI3K pathway and the DDR pathway in TNBC

Abstract The phosphoinositide 3-kinase (PI3K) pathway signals not only for cell survival and proliferation in tumor cells but also controls DNA damage repair (DDR) and maintains HR (homologous recombination) steady-state the translational significance of which has been reported [Juvekar A. et al., 2012]. In breast cancers (BC), alterations of the PI3K pathway genes are both subtype-specific as well as contextual, and alterations of DDR pathway genes are one such contextual event occurring with the upregulation of the PI3K pathway. We hypothesized that there is contextual cooperation between the cellular signals of the PI3K and DDR pathways. We sought to identify the co-alterations of the PI3K and DDR pathway genes in our triple-negative BC (TNBC) patient cohort to (A) interrogate the contextuality of such alterations and (B) understand the mechanism of the contextual cooperation using an algorithmically chosen combination of pathway targeted drugs. We analyzed the somatic alterations profile of genes (FoundationOne, USA) in 264 BC patients (Avera Cancer Institute, SD, USA). We experimentally validated the cooperation between the pathways using alteration-guided targeted inhibitors; isoform-specific PI3K and PARP inhibitor(s) in the TNBC model, to demonstrate the efficacy of a combination of a node-specific targeted inhibitor(s) of the two pathways. The predominant type of mutation of genes in the PI3K pathway in our patients with TNBC was found in PTEN (Y68C, Y180*, loss, loss exons 1-5, and deletion exon1) and PIK3CA (amplification, E545K, H1047R). The other common mutation found was in TP53 (>80%) and somatic BRCA1/2 (~15%) genes. The interaction between the two pathways was evaluated, applying STRING10 to test the association at the highest 0.900 confidence views. The highest level of efficiency of drugs is demonstrated following the treatment of p110beta inhibitor (AZD 6482) in combination with PARP inhibitor (Olaparib/Talazoparib) plus DNA damaging agent (carboplatin) in BRCA-incompetent PTEN-null TNBC cells (SUM149) as compared to the efficiency of a combination of a PI3K pathway targeted inhibitor (of p110alpha) with a PARP inhibitor in BRCA-competent PTEN WT, but PIK3CA altered TNBC cells (BT20). The context-dependent synergy between the PI3K and DDR pathways in the TNBC model is comprehended at the levels of (1) load of DNA damage, (2) PARP activity, (3) of BRAC1/2 competency or HRD scores, and (4) mode of upregulation of PI3K pathway. We present an algorithm for a rational combination of the PI3K and the DDR pathway targeted drugs in TNBC. Citation Format: Nandini Dey, Jennifer Carlson Aske, Pradip De. Linking proliferative signal to DNA-damage signal in a tumor cell: A contextual synergy between the PI3K pathway and the DDR pathway in TNBC [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr PD3-02.

Abstract 371: A single-center retrospective review assessing the use of tumor mutation burden as a predictor of therapeutic success in patients receiving immunotherapy

Abstract Background Cancer is a genetic disease in which cells may accumulate somatic mutations. The measurement of the frequency these somatic mutations occur is referred to as tumor mutational burden or TMB. A minority of these mutations may give rise to neoantigens that could in turn be recognized and targeted by the immune system. The more somatic mutations a tumor develops, the more likely these neoantigens are to form. Recent studies, namely KEYNOTE-158, found high TMB status to be associated with improved outcomes in patients receiving pembrolizumab monotherapy. Materials and Methods This was a single-center retrospective study that analyzed 73 patients who received cancer treatment at Avera Cancer Institute between June 2016 and July 2019. Patients were included/excluded from the final analysis based on having received at least one dose of pembrolizumab, ipilimumab, and/or nivolumab. Information was collected on patient characteristics, treatment, and clinical outcomes. The primary outcomes were complete and partial response rates and were assessed objectively based on a composite of radiographic reports, physician documentation, and treatment course. Secondary outcomes were clinical outcomes in patients with PD-1 and/or PD-L1 expression, clinical outcomes in patients receiving mono-immunotherapy vs combination therapy, and clinical outcomes based on the line of treatment in which immunotherapy was utilized. Results A total of 34 patients met the inclusion criteria of having a high TMB value (10 mutations/megabase) and having received one dose of pembrolizumab, ipilimumab, or nivolumab. Primary Outcomes•16 patients experienced a partial response (AR = 0.47) and 6 of these patients experienced a complete response (AR = 0.17) Secondary Outcomes•Absolute risk with prior TMB information (PR 0.43, CR: 0.17)•Absolute risks for monotherapy (PR: 0.375, CR: 0.125) vs combination therapy (PR: 0.556, CR: 0.375)•Average line of treatment for TF, PR, and CR were 2.24, 2, and 1.83 respectively. Discussion Studies like KEYNOTE-158 found a significant correlation between high TMB and improved clinical outcomes in patients receiving checkpoint inhibitors. However, in this cohort of patients high TMB status was not a good predictor of therapeutic success compared to the data presented in KEYNOTE-001, CHECKMATE-057, OAK, or PACIFIC. While there are limitations associated with the sample size, the data support that checkpoint therapy benefits patients when it is used earlier in their treatment course and combined with other treatments. Further exploration is required to determine the most appropriate cut point for calling a patient TMB high as well as how TMB and PD-L1 predict response to specific therapies. Citation Format: Khai Nguyen, Bing Xu, Rachel Elsey, Tobias Meissner, Casey Williams. A single-center retrospective review assessing the use of tumor mutation burden as a predictor of therapeutic success in patients receiving immunotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 371.

Abstract 1385: Clinical outcomes between obese and non-obese breast and gynecological cancer patients with alterations in the PI3K/AKT/mTOR pathway

Abstract Purpose Obesity has been shown to be strongly associated with the development of breast and gynecologic cancers. PIK3CA is one of the most commonly altered genes in solid tumors, and patients who have alterations are routinely initiated on therapies that target this pathway. However, response can vary greatly between patients, and the reason for differences in response has yet to be completely understood. Obesity has been shown to alter cancer metabolism and further dysregulate the PI3K/AKT/mTOR pathway which may affect response to target therapy. L. Cantley and colleagues suggest that the state of consistent hyperinsulinemia, which is common in obesity, can compromise the clinical benefit of PI3K-pathway targeted therapy, as insulin is a known potent stimulator of this pathway. Therefore, the purpose of this study was to compare clinical outcomes between obese and non-obese patients on pathway-directed therapy. Methods A retrospective analysis was performed on 140 patients with breast, ovarian, cervical, or endometrial malignancies at Avera Cancer Institute. Female patients with a documented oncogenic PIK3CA alteration were included in the study. Overall survival (OS) and progression free survival (PFS) were the primary endpoints. BMI groups were determined by using existing clinical categories of obesity as defined by the CDC. Patients were stratified into 2 BMI groups: Group A 25 kg/m2 and Group B 25 kg/m2. The Kaplan-Meier method was used to derive time-to-event estimates and test for significance. A cox proportional-hazard model was utilized to determine the association between survival time for patients with BMI being the predictor variable. Results Of the 140 patients, 106 patients had breast cancer, 21 patients had endometrial cancer, 9 patients had ovarian cancer, 3 patients had cervical cancer, and 1 patient had vaginal melanoma. There were 52 patients in Group A and 88 patients in Group B. 25 of the 140 patients had documented PIK3CA alterations but were never initiated on targeted therapy. Group B was found to reduce the hazard by a factor of 0.63 (p=0.09). The subset of Group B with PI3K/mTOR targeted therapy was found to reduce the hazard by a factor of 0.43 (p=0.008). Among the 43 patients who were included in PFS analysis, it was found that there was no statistically significant (p=0.6) improved PFS between the two groups. Conclusion In this analysis, patients with a PIK3CA mutation and who had a higher BMI had an improved response rate from targeted therapy and overall survival than compared to patients with a lower BMI. Treatment lines prior to initiation of targeted therapy varied greatly, and differences in the multiple types of malignancies studied in this analysis was a limitation. More prospective studies that are statistically powered are warranted in order to assess the true impact of obesity on improved OS compared to patients with a BMI 25. Citation Format: Diana Kim, Bing Xu, Rachel Elsey, Tobias Meissner, Casey Williams. Clinical outcomes between obese and non-obese breast and gynecological cancer patients with alterations in the PI3K/AKT/mTOR pathway [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1385.

Abstract 683: Impact of smoking cessation and anxiety on hypersensitivity reactions in cancer patients

Abstract Purpose: Little is known about the physiological impact of smoking cessation on a patient with cancer. Smoking cessation immediately after a cancer diagnosis likely induces a nicotine withdrawal syndrome that drastically alters catecholamine production and activity and may negatively impact a patient's mental health. Studies have demonstrated that stress-related catecholamines may negatively affect cancer progression, but data regarding the acute effects on immune system function is lacking. The molecular mechanisms of hypersensitivity to taxane chemotherapy are not well defined, but for a majority of patients that develop a reaction to paclitaxel, the reaction occurs with the first or second infusion. Our hypothesis is patients that are highly anxious are more likely to develop a reaction to chemotherapy such as paclitaxel, particularly if they have a recent history of nicotine addiction and are trying to quit. Methods: A retrospective chart review of patients with breast or gynecological cancers was conducted at Avera Cancer Institute. A total of 58 female patients with a history of a hypersensitivity reactions to taxane chemotherapy were included. Data collected on patient characteristics included, smoking history, history of depression or anxiety, and onset of hypersensitivity reaction. The primary outcome was strength of association between nicotine exposure and onset of reaction, based upon odds ratio and relative risk. Secondary outcomes included the effects of anxiety and nicotine withdrawal on clinical outcomes and anxiety-related impact on therapeutic execution. Results: Of the 58 patients with a history of taxane hypersensitivity, 12 (20.7%) had a diagnosis of anxiety, 19 (32.8%) were former smokers, and 2 (3.4%) were current smokers. Among the 12 patients who had a diagnosis of anxiety at the time of their reaction, 5 (41.7%) were documented to be former or current smokers. Patients previously exposed to nicotine were found to be more likely to experience a hypersensitivity reaction within cycle 1 of chemotherapy (Odds Ratio 1.26). The risk of experiencing a reaction within the first cycle was found to be 16% higher in those who were exposed to nicotine compared to those who were not. Conclusion: The results of our analysis indicate that recent nicotine addiction and anxiety may increase the likelihood of a taxane hypersensitivity reaction during cycle 1. Those without a smoking history mainly experienced reactions during cycles 2, 3, or 4, which reinforced our findings. Limitations associated with this study include small sample size and the challenges of interpreting clinical notes in the electronic medical record. A larger analysis is required to confirm our results and data collection is ongoing. Citation Format: Devon C. Barry, Natalie Hartung, Casey Williams. Impact of smoking cessation and anxiety on hypersensitivity reactions in cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 683.

Abstract 1381: Impact of PI3K/mTOR inhibitors on the development of taxane resistance

Abstract Background:Preclinical evidence suggests PI3K pathway activation is associated with resistance to taxane chemotherapy as well as that treatment with a PI3K or mTOR inhibitor concomitantly with paclitaxel may reduce the occurrence of taxane resistance. Data of alpelisib in combination with paclitaxel showed PR or SD in 14 out of 18 patients in the study who were previously treated with paclitaxel. A second early phase study showed a 67% ORR in heavily pretreated patients given PI3K and mTOR inhibitors in addition to paclitaxel for patients considered taxane resistant or refractory prior to study enrollment. Interestingly, a trial participant with metastatic breast cancer was effectively maintained on paclitaxel after participation in the trial had stopped. Therefore, the purpose of this analysis was to examine further whether taxane chemotherapy administered after the use of PI3K/mTOR inhibitors may reduce the development or impact of taxane resistance. Methods: A retrospective analysis was performed on patients with breast and gynecologic cancers at Avera Cancer Institute. Patients who had an oncogenic PI3K pathway alteration and received at least one cycle of taxane chemotherapy followed by at least one dose of a PI3K or mTOR inhibitor were included. Descriptive statistics were used to determine primary and secondary outcomes. Clinical benefit was defined as the duration of time achieved with stable disease or remission from a treatment before a successive therapy was warranted. The primary outcome was defined as duration of clinical benefit achieved from each therapy. The secondary outcomes were defined as survival from date of diagnosis of metastatic disease or recurrence and reasons for discontinuation of targeted therapy. Results: Thirty-six patients were eligible for inclusion in the analysis. PIK3CA E545K (n=7) and PIK3CA H1047R (n=10) were the most common mutations identified. Thirty-four patients received a median duration of benefit of 8 months from treatment with a PI3K or mTOR inhibitor. Twenty patients received paclitaxel after treatment with a PI3K or mTOR inhibitor and received a median duration of benefit of 6 months. Survival for evaluable patients was a median of 3.3 years, with 11 patients still alive. Main reasons for discontinuation of therapy were side effects, including rash, pneumonitis, acute kidney failure and mucositis, or progression in disease (n=20). Conclusion: Some patients treated with PI3K or mTOR inhibitors received additional benefit from subsequent taxane therapy when considered to be resistant to taxane treatment. Several different regimens were used and in various orders; however, earlier use of PI3K or mTOR inhibitors with paclitaxel trended toward better patient outcomes with fewer lines of treatment. Adequately controlled and powered prospective studies are needed to determine a true relationship between PI3K and/or mTOR inhibitor therapy and re-initiation of taxane sensitivity. Citation Format: Jayda Nicole Esplund, Bing Xu, Rachel J. Elsey, Tobias Messner, Casey B. Williams. Impact of PI3K/mTOR inhibitors on the development of taxane resistance [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1381.

Abstract P3-03-09: Dual targeting of BCL2 and MDM2 as a novel therapeutic strategy in ER+ breast cancer model

Abstract Background: Apoptosis is the therapeutic goal following the administration of anti-cancer drugs. BCL2 and p53 are two critical nodes in the apoptosis signaling pathway. BCL2 is overexpressed in approximately 80% of primary ER+ breast cancer (BC) patients (Merino D et al. Oncogene 2016). Venetoclax is a BCL2 selective inhibitor found to be active in clinical trials for solid tumors, including ER+ BC breast cancer (Lok SW et al. Cancer Discovery 2019). MDM2/MDM4 is a proliferating protein involved in tumorigenesis via degradation of p53. In our ER+ BC breast cancer cohort (Avera Cancer Institute, Sioux Falls, South Dakota), we observed TP53 and MDM2/4 alterations in 25% and 14% of patients respectively. Aim: Here, we hypothesize that concomitant p53 activation (by an MDM2 inhibitor, e.g., AMG232) and BCL2 inhibition (by venetoclax) induce maximum apoptosis and markedly reduce tumor cell proliferation in ER+/TP53 WT BC cells. Methods: We analyzed the expression pattern of 129 ER+ BC breast cancer patients whose tumors were subjected to comprehensive genomic profiling [FoundationOne]. We tested the anti-proliferative and apoptotic activity of venetoclax alone, AMG 232 alone, and a combination of venetoclax plus AMG 232 along with fulvestrant in ER+ BC breast cancer cells (MCF7, Zr-75-1, & MDA-MB415). Results: 1) AMG 232 binds the MDM2 protein, blocks MDM2-p53 interaction, and induces p53 expression and activity, 2) p53 effector molecule p21 is robustly induced following the treatment of AMG 232, 3) the anti-proliferative activity of venetoclax or AMG232 was observed by 3D-ON-TOP clonogenic assay and real-time monitoring in an IncuCyte Zoom, 4) ER+ /TP53 wild-type (WT) cell lines exhibited an increase in annexin V positivity (initiation of apoptotic activity) following venetoclax or AMG 232 treatment, 5) importantly, a combination of venetoclax plus AMG232 robustly induced the apoptotic markers e.g. cleaved-CASPASE3/7 and cleaved PARP1 protein expression in all ER+ BC cell lines, 6) high mitochondrial depolarization was also observed following the combination of treatment, and 7) similar to protein expression data, mRNA data also showed that pro-apoptotic/cell cycle inhibitor transcripts such as p21 and PUMA mRNA expression were significantly increased and pro-survival transcripts such as survivin and stathmin mRNA expression were significantly decreased following the combination treatment. Conclusion: Our data reveal the potential of simultaneously targeting these two apoptosis regulators and provides a rational basis for clinical testing of this therapeutic approach for ER+ BC breast cancer patients that retain WT-TP53. Citation Format: Pradip De, Jennifer Carlson Aske, Poulin Pocha, Michael Sulaiman, Ethan Thompson, Nandini Dey. Dual targeting of BCL2 and MDM2 as a novel therapeutic strategy in ER+ breast cancer model [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P3-03-09.

Abstract P3-03-13: Testing algorithmic basis for combinations of targeted drugs by a mechanism-based laboratory friendly identification of apoptosis in live breast cancer cells

Abstract Background: The mechanism of induction of apoptosis has been one of the features to characterize and classify anti-tumor drugs. We have standardized a mechanism-based approach to identify apoptosis in live tumor cells by triple co-fluorescence (De et al., 2018; SCIENTIFIC REPORTS). Our protocol tests three crucial features of apoptosis; the enzymatic activity of executioner caspase3, cell surface presentation of caspase-dependent phosphatidylserine and mitochondrial function. Navigating the genomic landscape of tumors in patients with Triple Negative Breast Cancers (TNBC) at Avera Cancer Institute, we have identified algorithm for the rational combination of PI3K-pathway (PP) drugs. Aim: Here we present the results of testing the rational combinations of PP-targeted drugs on apoptosis using our mechanism-based laboratory friendly procedure. Methods: Our protocol co-stains live tumor cells in real time with NucView488 Casp3substrate (N), CF594AnnexinV (A), and MitoViewBlue (M). We have used carboplatin and targeted-drugs like olaparib, ABT888, BMN673, AZD2014, GDC0980, and AZD5363 in BRCA-WT (MDA-MB231, MDA-MB468) and BRCA-incompetent (SUM149) TNBC cells. Imaging of cells using simultaneous live/dead cell markers (Calcein AM green/EthD-1 red) was used for validation. Results: We retrospectively analyzed genomic data [FoundationOne] from 100 consecutive patients seen in our center from 2014. 137 genes were altered including 12 PP and 11 DNA-repair genes. We used AnnexinV-PE staining (Accuri C6), confocal IF imaging and WB expression of apoptotic signals and mitochondrial potential (TMRE-A) as validation criteria following different combinations. Treatment with the rational combination(s) like PARP inhibitor(s) plus carboplatin and PP inhibitor decreased proliferation, induced profound early apoptotic events, along with increased apoptotic signaling and increased mitochondrial depolarization in real time. Dual treatment also blocked cytoplasmic M staining while increasing both nuclear N substrate staining and membranous A staining. Control cells had higher Calcein AM positive (live) cells and fewer EthdD-1 stained red nuclei of dead cells than treated cells. Merged images (M+N+A) showed 100% mutual exclusivity between M and N or A stains in both control and treated cells as determined by overlap and colocalization coefficients. Conclusion: Our method of staining identified the apoptosis following treatment of drug-combination(s), which was based on the genomic alteration(s) present in TNBC patients. Citation Format: Nandini Dey, Jennifer Carlson Aske, Pradip De. Testing algorithmic basis for combinations of targeted drugs by a mechanism-based laboratory friendly identification of apoptosis in live breast cancer cells [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P3-03-13.

Mutation-Driven Signals of ARID1A and PI3K Pathways in Ovarian Carcinomas: Alteration Is An Opportunity.

The chromosome is a functionally dynamic structure. The dynamic nature of chromosome functionally connects it to almost every event within a cell, in health and sickness. Chromatin remodeling system acts in unison with the cell survival pathway in mediating a variety of cellular functions, including mitosis, differentiation, DNA damage repair, and apoptosis. In humans, the 16 SWI/SNF complexes are a class of nucleosome remodelers, and ARID1A, an epigenetic tumor suppressor, is a member of mammalian 17 chromatin remodeling complex, SWI/SNF. Alterations of chromatin remodeling system contribute to tumorigenic events in various cancers, including ovarian cancers. Oncogenic changes of genes of the PI3K pathway are one of the potential genetic determinants of ovarian carcinomas. In this review, we present the data demonstrating the co-occurrence of mutations of ARID1A and the PI3K pathway in our cohort of ovarian cancers from the Avera Cancer Institute (SD, USA). Taking into account data from our cohort and the cBioPortal, we interrogate the opportunity provided by this co-occurrence in the context of mutation-driven signals in the life cycle of a tumor cell and its response to the targeted anti-tumor drugs.

Survivorship Care Plans: Health Actions Taken and Satisfaction After Use.

To examine the use of and assess patient satisfaction with survivorship care plans (SCPs). 189 cancer survivors recruited from five cancer treatment center locations (Avera Cancer Institute in Aberdeen, Mitchell, Sioux Falls, and Yankton; Sanford Cancer Center in Sioux Falls) and one auxiliary specialty center (Urology Specialists in Sioux Falls), all in South Dakota. A written survey was completed by participants before and three months after receiving an SCP. Associations between demographics and cancer-related characteristics and use of the SCP were evaluated using chi-square tests. Logistic regression was used to determine factors associated with any use of the SCP, health actions attributable to the SCP, and satisfaction with the SCP. The most frequently reported uses of the SCP were to share with spouse or partner, inform about symptoms, and ask physician or nurse about concerns. SCP use, health actions taken, and satisfaction with the SCP were associated with gender, marital status, and main cancer type. Nurses should promote SCPs because they are valued and used by survivors for follow-up care.

Abstract 3891: Tolerability and outcomes of trametinib and everolimus combinations in advanced solid tumors

Abstract Purpose Aberrations in the PI3K/AKT/mTOR and MAPK pathways are routinely found in patients with cancer. To date, safe and effective combinations of drugs that hit both pathways concurrently are scarce. Data from Tolcher and colleagues have shown that the combination of trametinib and everolimus is intolerable at the doses and schedules studied in a phase 1 trial for patients with advanced solid tumors. The purpose of this analysis was to determine the tolerability and outcomes for patients prescribed trametinib and everolimus utilized in 2 open trials at our center. Methods A retrospective analysis was performed on 31 patients with various tumor types at the Avera Cancer Institute with approval from the IRB. Patients who received at least one dose of trametinib in combination with everolimus in addition to concurrent therapies were included. Fifteen patients (48%) had undergone ≥ three lines of therapy prior to initiation of trametinib and everolimus. Descriptive statistics were used to determine primary and secondary outcomes. Tolerability was defined as number of dose adjustments or holds in therapy for each regimen. Primary outcome was based on comparisons between tolerability of the drug regimens and the schedule of doses, line of therapy, concurrent cytotoxic agents, and primary tumor type. A secondary outcome calculated the PFS of eligible patients (n=5) who had different trametinib and everolimus regimens. Results Twenty-three patients (74%) tolerated various combinations of trametinib and everolimus, of which 16 received treatment for more than 3 months. Eight patients (26%) discontinued treatment due to adverse events, of which six patients did so within the first 3 months of treatment. Average time to first hold or reduction in therapy due to toxicities from any trametinib and everolimus regimen was 2.5 months. Most common adverse events were fatigue (n=19), mucositis (n=18), and elevated LFT's (n=17). The most common regimen utilized (n=23) was initiated at trametinib 1 mg daily with everolimus 5 mg every Mon, Wed, Fri. Patients on this regimen experienced dose-limiting toxicities at an average of 1.4 months after initiation. Trametinib and everolimus were most commonly started as ≥ the fourth line of therapy. PFS for evaluable patients was 6.5 months; two patients continue to respond. PIK3CA (n=10) and KRAS (n=9) were the most common mutations identified. Conclusion In this analysis, the combination of trametinib and everolimus has shown to be tolerable in many patients with advanced solid tumors, and has also demonstrated clinical efficacy for patients with heavily pre-treated disease. However, the regimens utilized were highly individualized, thus notable variability existed between patient therapies. Therefore, to determine an optimal dose and schedule to evaluate the overall efficacy of trametinib and everolimus combination, an adequately powered and controlled study would be required. Citation Format: Jason Patterson, Cory Perry, Joe Windscheffel, Rachel Elsey, Kirstin Williams, Nandini Dey, Pradip De, Brian Leyland-Jones, Casey Williams. Tolerability and outcomes of trametinib and everolimus combinations in advanced solid tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3891.

Abstract 4554: Assessment of the efficacy and safety of checkpoint inhibitors in the treatment of solid-tumor malignancies in a community cancer hospital

Abstract Introduction: High dose chemotherapy, radiation, and/or surgical resection have historically been the standard therapy for patients with progressive malignancies. However, promising studies have shown immunotherapy may improve overall survival and reduce tumor burden in advanced disease. Checkpoint inhibitors, such as PD-1 inhibitors pembrolizumab and nivolumab and PD-L1 inhibitor atezolizumab, are approved for use in several solid tumors, but the response to these agents has been limited. This study was designed to identify predictors for the therapeutic response to immunotherapy agents in a community cancer hospital. Procedures: A retrospective review using the electronic medical record system was done to identify 43 patients treated with immunotherapy at Avera Cancer Institute. The inclusion criteria included patients who had solid organ malignancies, received checkpoint inhibitor-based immunotherapy between May 31, 2014 and May 31, 2017, and completed next generation sequencing of tumor DNA. The exclusion criteria included patients who were less than eighteen years of age, pregnant, or received care in an outreach clinic when records were not available. Data obtained from the records included age, sex, diagnosis, treatment history, immunotherapy agent used, start and end date of immunotherapy agent, clinical outcome, pathology results, adverse reactions, and next generation sequencing results of tumor DNA. The collected data was assessed for patient characteristics and biomarkers that predicted responses to immune checkpoint blockade in solid tumors. Disease progression was assessed in correspondence with the response evaluation criteria in solid tumors guidelines. Results: A total of 43 patients were included, 14 male and 29 female. The median patient age was 66 years old. The main malignancies included were, breast (11 patients), lung (10 patients), and ovarian (7 patients). On average, the patients were treated with three previous lines of therapy before receiving immunotherapy treatment. The most common immunotherapy agent was pembrolizumab, with 28 of the patients receiving this, followed by 14 patients treated with nivolumab and one treated with atezolizumab. The median time patients on immunotherapy was 118 days. Patients with longer duration of immunotherapy, fewer previous treatment lines, and higher tumor mutational burden (TMB) had the best response to checkpoint inhibitors. Conclusions: The predictive biomarkers found in this study can be used to assist in patient selection for immunotherapy in the clinical setting, including TMB and the number of lines of previous therapy. Further studies will continue to find predictors of non-response and hyperprogressors. We hope to further evaluate patients who experienced a durable response to create new hypotheses about indicators of response. Citation Format: Rachel Elsey, Nathan Smith, April Lick, Lauren Metzger, Casey Williams, Brian Leyland-Jones, Ping Ye. Assessment of the efficacy and safety of checkpoint inhibitors in the treatment of solid-tumor malignancies in a community cancer hospital [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4554.