Duke Cancer Center Research Articles

Acquired gene alterations potentially related to resistance to anti-HER2 therapy in HER2-positive metastatic colorectal cancer (mCRC).

277 Background: While HER2-targeted therapies benefit patients (pts) with advanced HER2-positive mCRC, the development of resistance remains inevitable. This study aims to explore the landscape and frequency of genetic alterations putatively associated with acquired resistance to anti-HER2 therapy in HER2-positive mCRC. Methods: In this retrospective-multicenter international study involving Mayo Clinic, Duke Cancer Center and National Cancer Center Hospital East (Japan), we descriptively compared comprehensive genomic analyses from tissue or blood samples of pts with HER2-positive CRC pre-treatment and post-treatment with HER2-targeting agents. Results: A total of 36 pts were included in this study. 29 (80%) had HER2-positive mCRC as confirmed by immunohistochemistry (IHC) and fluorescent in situ hybridization (ISH), the remaining pts had HER2 amplification detected on blood or tissue . 34/36 (94%) pts were administered their first anti-HER2 agent after progressing on ≥2 prior lines of treatment. The most common anti-HER2 regimen administered was trastuzumab/pertuzumab (50%, 18/36), followed by trastuzumab-tyrosine kinase inhibitors (TKIs) (tucatinib or neratinib) (30%, 11/36) and trastuzumab deruxtecan (14%, 5/36). Putative genomic mechanisms of acquired resistance were detected in 72% (26/36), while the remaining pts lacked new genomic alterations that might explain resistance to anti-HER2 therapy, suggesting alternative escape mechanisms. Acquired alterations in downstream or alternate bypass pathways were identified in 72% (26/36) of pts; most commonly in the RAS/RAF pathway and in EGFR (34.6%, 9/26 each), followed by 27% (7/26) of pts with MET point mutations (mts) and amplification; activating muts in PI3K/AKT and in 27% (7/26), most commonly CDK12 (60%, 4/7) . HER2 receptor alterations were detected in 3 pts (8.3%), all of whom received trastuzumab-tucatinib and included HER2 L755S, HER2 V777L, HER2 D769Y, HER2 G727A and HER2 S310F, which are known to cause resistance to , however, information about tucatinib resistance is not yet available. Other altered pathways included AR, RB, NOTCH and HRD. Two pts lost HER2 expression on blood and tissue NGS post anti-HER2 therapy. Conclusions: The emergence of resistance might be in part related to acquired alterations that constitutively activate signaling pathways parallel or downstream of HER2, bypassing HER2 inhibition. Additional histologic studies, deep mutational scanning, larger populations and correlative analysis are needed to validate these findings.

Abstract PS08-09: Impact of HER2 expression dynamics on the real-world activity of trastuzumab deruxtecan for metastatic breast cancer (RELIEVE)

Abstract Background: trastuzumab deruxtecan (T-DXd) is a standard treatment for patients (pts) with HER2-positive (HER2+) and HER2-low metastatic breast cancer (MBC). HER2-low expression has been shown to be a highly unstable biomarker, and no data exists on the activity of T-DXd among pts with changes in HER2 status over time. Furthermore, limited data exists on the performance of regimens administered after progression on T-DXd. Methods: We analyzed data for pts with MBC receiving T-DXd at Dana-Farber Cancer Institute between 7/2017 - 2/2023 and at Duke Cancer Center between 3/2020 - 4/2022. The disease was categorized HER2+ if IHC 3+ or ISH-amplified at any time point; HER2-negative cases were categorized as HER2-low (IHC 2+/ISH- or IHC 1+) or HER2-0 (IHC 0) based on the last biopsy before T-DXd; the HER2 status for the primary tumor and at first metastatic diagnosis were also collected. We determined time to next treatment (TTNT), overall survival (OS), toxicities with T-DXd, TTNT based on dynamic HER2 status and TTNT with post-T-DXd regimens. Genomic data was available for 58 pts using an in-house NGS assay on archival tumor samples. Results: A total of 191 pts were included in the analysis (126 HER2+, 44 HER2-low, 21 HER2-0). Median age at metastatic diagnosis was 50.9 (range 21 - 78), 26% had de-novo MBC and 38% had history of brain metastases before T-DXd. The proportion of hormone receptor (HR)-positive tumors based on the last biopsy prior to T-DXd was 53% in HER2+, 68% in HER2-low and 57% in HER2-0; pts within each cohort had received a median of 2 prior lines of chemotherapy before T-DXd (range 0 - 9). With a median follow-up of 10.4 months, median TTNT was 10.4 months for HER2+, 7.6 months for HER2-low and 3.7 months for HER2-0 MBC (p < 0.001). Switch in HER2 status between primary tumor and pre-T-DXd biopsy significantly impacted outcomes, with the shortest TTNT observed in pts switching from HER2-low to HER2-0 (TTNT 3.0 months) compared with 5.6 months if switching from HER2-0 to HER2-low, and 9.4 months if having stable HER2-low status (p=0.006). Conversely, HER2 status switch within the metastatic setting did not impact outcomes (Table 1). No difference in TTNT was seen regardless of HR status (negative vs positive, 7.4 vs 10.2 months, p=0.25) or number of prior chemotherapies (≤2 vs >2, 10.1 vs 8.8 months, p=0.50). Median OS is shown in Table 1. At last follow-up, 55 pts remain on T-DXd (28.8%), 108 progressed (56.5%), 28 stopped due to toxicity (14.7%). A total of 22 pts (11.5%) developed interstitial lung disease (ILD, 6.2% grade [G]1, 3.1% G2, 1.6% G3, 0.5% G4, no G5). ILD occurred after a median of 8 months from T-DXd initiation and resolved in 63.6% of the cases, with a median time to resolution of 4 months (2 months for grade 1 events). 5 pts (2.6%) developed cardiotoxicity. T-DXd was dose reduced in 61 pts (31.9%), most often for fatigue (14.7%), nausea/vomiting (9.9%) or hematological toxicity (6.3%). Among 105 pts receiving post-T-DXd treatments, TTNT was 4 months for HER2+, 3.1 months for HER2-low and 4.3 months for HER2-0 MBC (p=0.62). Pts with HER2-negative tumors and ERBB2 hemizygous deletions (6/58, 10.3 %) had a TTNT with T-DXd of 4.1 months, vs 7.6 months without ERBB2 deletions (p=0.41). Additional biomarker data will be presented at the meeting. Conclusions: T-DXd showed promising real-world activity in pretreated pts with MBC, with the longest TTNT observed among pts with HER2+ disease or with stable HER2-low disease over time. Real world TTNT is relatively short post-T-DXd and further studies evaluating resistance mechanisms and optimal treatments in this setting are needed. Table 1 – TTNT and OS among patients with metastatic breast cancer receiving T-DXd and post-T-DXd regimens according to HER2 status The activity of T-DXd significantly differed according to the HER2 status of the disease, with the longest TTNT observed among patients with HER2+ disease (at any timepoint in time) and among patients with stable HER2-low disease over time. Regimens administered immediately after T-DXd achieved a similar performance irrespective of the HER2 status of the disease, with a TTNT ranging between 3.1 and 4.3 months. Citation Format: Paolo Tarantino, Melissa Hughes, Ross Kusmick, Laura Alder, Alyssa Pereslete, Laura Noteware, Heather Moore, Amanda Van Swearingen, Tianyu Li, Hersh Gupta, Kalie Smith, Stefania Morganti, Janet Files, Kerry Sendrick, Simone Buck, Deborah Dillon, Rinath Jeselsohn, Yvonne Li, Andrew Cherniack, Aleix Prat, Nay Nwe Nyein Chan, David Rimm, Giuseppe Curigliano, Sarah Sammons, Carey Anders, Nancy Lin, Sara Tolaney. Impact of HER2 expression dynamics on the real-world activity of trastuzumab deruxtecan for metastatic breast cancer (RELIEVE) [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PS08-09.

"More than conquerors": a qualitative analysis of war metaphors for patients with cancer.

Meaning-making is fundamental to the cancer experience and communication within cancer care is saturated with metaphors. The objective of this study was to better understand the impact and function of war metaphors among patients with cancer. Patients at the Duke Cancer Center were purposively sampled for inclusion based on type and stage of their cancer. Each patient underwent a semi-structured interview to explore their use of metaphors in their lived experience with cancer. Qualitative interviews broadly explored two key areas of interest: (1) frequency and use of metaphors to describe cancer diagnosis, treatment, or survivorship; (2) function and impact of the war metaphor on the patient experience of cancer. Fifteen participants with either breast, lung, or colorectal cancer were interviewed. Most patients used metaphor themes of journey, war, and mystery to describe their cancer. All patients with non-metastatic disease used war metaphors and described how these metaphors facilitated meaning-making by promoting positivity and situating cancer within a larger life story. The few patients who did not use war metaphors had metastatic disease, and they explained that war metaphors were unhelpful due to feeling a lack of control over their metastatic disease and outcomes. The war metaphor should remain an integral part of cancer care. Disregarding war metaphors robs patients of an important framework for meaning-making-one that may promote strength, continuity, and resilience in navigating cancer.

Body composition in patients with metastatic renal cell carcinoma receiving ipilimumab plus nivolumab.

e16517 Background: Body composition (comp) is an increasingly recognized prognostic indicator in patients with cancer, but there are limited data regarding body comp measurements in patients with metastatic renal cell carcinoma (mRCC) treated with immune checkpoint inhibitors. The goal of this study was to assess baseline body comp measurements and rates of sarcopenia in patients with mRCC receiving ipilimumab + nivolumab (ipi/nivo) as first-line systemic therapy and examine potential associations with overall survival (OS). Methods: We conducted a retrospective analysis of all patients with mRCC treated with first line ipi/nivo at Duke Cancer Center prior to June 1, 2021, who had a CT scan within 6 weeks of ipi/nivo initiation. CT images were segmented and measured with Automatic Body composition Analyser using Computed tomography image Segmentation (ABACS) software (Voronoi Health Analytics). Areas of skeletal muscle (SM), subcutaneous fat (SF), and visceral fat (VF) at the level of the 3rd lumbar vertebra were measured and converted to indices by dividing by height (m2) (Area SMI, SFI, VFI). Volumes of SM, SF, and VF between the 1st and 5th lumbar vertebrae were measured and converted to indices by dividing by the height of the measured slab (Volume SMI, SFI, VFI). Sarcopenia was defined as SMI < 55cm2/m2 in men and < 39cm2/m2 in women based on prior studies. Medical records were retrospectively reviewed to identify demographic and oncologic details. Effects of body comp measures on overall survival were assessed using Cox proportional hazard models, which were adjusted for IMDC risk, age, and sex. Results: 104 patients met study criteria and had an analyzable baseline CT scan. Median age was 62 (range 37 – 81). 71% of patients were male. Median body mass index (BMI) was 27.2 (range 17.8 – 43.6). IMDC risk score was 12% favorable, 63% intermediate, 20% poor, and 5% unknown. Median follow up time was 19.98 months. Median survival was 39.79 months (95% CI 27.01, NA). 1-year survival rate was 0.81 [95% CI 0.73, 0.89] and 2-year survival rate was 0.68 [95% CI 0.59, 0.79]. 77 of 104 patients (74%) met the definition of sarcopenia prior to treatment. No body comp measurements were associated with OS. Effects of body comp measurements on overall survival are shown in table 1. Conclusions: Baseline body comp measures were not associated with OS in a population of patients with mRCC receiving ipi/nivo as first-line systemic therapy. Changes in body comp over time may instead be of interest as potential biomarkers for OS in patients with mRCC receiving ipi/nivo. [Table: see text]

Study protocol for a randomised trial evaluating the non-inferiority of stepped palliative care versus early integrated palliative care for patients with advanced lung cancer

IntroductionIntegrating palliative care (PC) early in the illness course for patients with serious cancers improves their outcomes and is recommended by national organisations such as the American Society of Clinical...

Upfront Targeted Tyrosine Kinase Inhibitor Therapy Improves Outcome in Patients with Myeloid/Lymphoid Neoplasms with Eosinophilia

▪BackgroundTo recognize the growing list of recurrent genetically defined eosinophilia driven by constitutively active tyrosine kinase fusion genes, the World Health Organization (WHO) created a provisional entity of myeloid/lymphoid neoplasms with eosinophilia (MLN-Eo) with rearrangement of PFGFRA, PDGFRB or FGFR1, or with PCM1- JAK2. These eosinophilic disorders are clinically and genetically heterogeneous. Annotating additional somatic mutations and relevant clinical features may have an impact on treatment selection and refine prognostication. In this study, we aim to describe the clinicopathologic characteristics and outcome with upfront targeted tyrosine kinase inhibitor (TKI) therapy in patients (pts) with MLN-Eo.MethodsWe retrospectively reviewed clinical and molecular data on 39 pts with newly diagnosed MLN-Eo with PDGFRA, PDGFRB, FGFR1, JAK2 or FLT3 rearrangement at Moffitt Cancer Center, Duke Cancer Center, and the UCSF Comprehensive Cancer Center. Clinical data was abstracted in accordance with institutional review board approved protocol. Pts were divided to two categories based on morphologic classification of the disease at diagnosis or at transformation: chronic phase and blastic phase disease. Each category was then divided into two subgroups: Cohort A) upfront TKI +/- other systemic therapy and Cohort B) no upfront TKI arm. Median time from chronic phase disease to blastic phase and median overall survival (mOS) (in whole cohort) were calculated using Kaplan Meier method and compared with log-rank test. Cox proportional hazards (PH) model was used to calculate hazard ratio (HR) in univariate analyses.ResultAmong the 39 pts included in the analysis, 22 pts had PDGFRA fusion (20)/activating mutations (2), 4 had PDGFRB, 7 had FGFR1, 2 had JAK2 (PCM1-JAK2 and BCR-JAK2), and 4 had FLT3 (3 ETV6-FLT3 and 1 FLT-3-TRIP11). Median age at first diagnosis of myeloid/lymphoid neoplasm was 54.5 years (range 9-76). Seventy-seven percents (30/39) were male. Chronic eosinophilic leukemia (CEL) was the most common clinical diagnosis and occurred in 11 pts (28%). Seven (18%) pts had both myeloid and lymphoid neoplasms either concurrently or sequentially. Sixteen (41%) pts presented with de-novo blastic phase at time of initial diagnosis.Among 23 pts who presented with chronic phase disease at diagnosis, nine patients did not receive TKI upfront. Five out of the nine patients (55%) developed blastic phase disease with a median follow up of 73 months. The median time to blastic phase was 45 months. No patients in the upfront TKI arm (n=14) had blastic transformation during follow up (Figure 1a, p<0.001).Among 21 pts who had blastic phase disease (16 pts with de-novo diagnosis and 5 pts with blastic transformations), 95% of them (20/21 pts) had treatment information and follow-up data available. At a median follow up of 37 months, 11 pts (55%) were deceased, and median OS was 44 months. Seven pts (35%) underwent allogeneic stem cell transplant (alloHSCT). Four patients received upfront TKI, and all of them achieved complete remission and were alive at the time of the study (Figure 1b). Among those pts, 2 had FLT3-ETV6 rearrangement, 1 with PDGFRA rearrangement and 1 with FGFR1 rearrangement. Two pts received single agent TKI only and two pts received TKIs followed by alloHSCT.In the univariate analysis, upfront TKI use was significantly associated with improved OS (HR 0.067, 95% CI [0.009-0.512], p=0.009). Complex cytogenetics at the time of initial diagnosis was associated with inferior OS, though statistical significance was not reached (table II).ConclusionOur data suggests that upfront TKI therapy is associated improved survival outcomes in pts with MLN-eo and is effective in preventing blastic transformation from chronic phase disease. As proposed, the driver oncogene most likely occurs in hematopoietic stem cells/progenitor cells in this entity. Upfront TKI can potentially suppress, even in some cases eradicate the malignant clone. The study is limited due to small sample size and retrospective nature, and larger study is needed to validate our observation. [Display omitted] DisclosuresSokol: Kyowa-Kirin: Membership on an entity's Board of Directors or advisory committees; Dren Bio: Membership on an entity's Board of Directors or advisory committees. Shah: Novartis: Consultancy, Other: Expenses; Pfizer: Consultancy, Other: Expenses; Amgen: Consultancy; Precision Biosciences: Consultancy; Kite, a Gilead Company: Consultancy, Honoraria, Other: Expenses, Research Funding; Pharmacyclics/Janssen: Honoraria, Other: Expenses; Acrotech/Spectrum: Honoraria; BeiGene: Consultancy, Honoraria; Incyte: Research Funding; Jazz Pharmaceuticals: Research Funding; Servier Genetics: Other; Bristol-Myers Squibb/Celgene: Consultancy, Other: Expenses; Adaptive Biotechnologies: Consultancy. Lancet: Agios: Consultancy; AbbVie: Consultancy; Celgene/BMS: Consultancy; Daiichi Sankyo: Consultancy; Astellas: Consultancy; BerGenBio: Consultancy; Millenium Pharma/Takeda: Consultancy; ElevateBio Management: Consultancy; Jazz: Consultancy. Kuykendall: Protagonist: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; BluePrint Medicines: Honoraria, Speakers Bureau; Prelude: Research Funding; Abbvie: Honoraria; Incyte: Consultancy; Novartis: Honoraria, Speakers Bureau; PharmaEssentia: Honoraria; Celgene/BMS: Honoraria, Speakers Bureau; CTI Biopharma: Honoraria. Padron: Stemline: Honoraria; BMS: Research Funding; Kura: Research Funding; Blueprint: Honoraria; Incyte: Research Funding; Taiho: Honoraria.

Evaluation of the Role and Impact of Ambulatory Clinical Pharmacists in an Academic Comprehensive Cancer Center.

IntroductionIn recent years, there has been significant growth of ambulatory oncology pharmacy, yet there is a paucity of published studies on the clinical activities and impact of ambulatory oncology clinical pharmacists. At Duke Cancer Center, dedicated pharmacist services are embedded in specialized outpatient oncology areas. Pharmacists document their clinical and administrative activities in the electronic health record. The primary objective of this study is to quantify and assess ambulatory oncology pharmacist interventions in clinics in a large academic comprehensive cancer center.MethodsFor the purposes of this single-center, retrospective, descriptive study, pharmacist interventions were collected, quantified, and described over a 6-month period from July 1 to December 31, 2015. The study evaluated the perceived contribution and impact of a pharmacist on patient care in ambulatory oncology clinics via a survey that was distributed to providers and nurses.ResultsIn the 6-month time period, there were 5,091 interventions spanning 3,967 patient encounters between nine ambulatory oncology clinic pharmacists. The average time per encounter in the 6-month time frame was 22.4 minutes. There were 92 respondents to the survey (61.7% response rate). Overall, responses showed that the clinical pharmacists add value to patient care and are integral members of the team.ConclusionsAlthough previous studies have described pharmacist activities in outpatient oncology clinics, this study showed a larger number and variety of clinical pharmacist activities in outpatient cancer clinics to improve patient care. Future directions include conducting prospective, controlled studies to link pharmacist activities to tangible outcomes.

Strategies for Referring Cancer Patients in a Smoking Cessation Program.

Most people who smoke and develop cancer are unable to quit smoking. To address this, many cancer centers have now opened smoking cessation programs specifically designed to help cancer patients to quit. An important question has now emerged—what is the most effective approach for engaging smokers within a cancer center in these smoking cessation programs? We report outcomes from a retrospective observational study comparing three referral methods—traditional referral, best practice advisory (BPA), and direct outreach—on utilization of the Duke Cancer Center Smoking Cessation Program. We found that program utilization rate was higher for direct outreach (5.4%) than traditional referral (0.8%), p < 0.001, and BPA (0.2%); p < 0.001. Program utilization was 6.4% for all methods combined. Inferring a causal relationship between referral method and program utilization was not possible because the study did not use a randomized design. Innovation is needed to generate higher utilization rates for cancer center smoking cessation programs.

Living with multiple myeloma: A life disrupted.

95 Background: Multiple myeloma (MM) an incurable cancer of the plasma cells is the second most common hematologic malignancy. Over 30,000 new diagnoses and over 12,000 deaths are attributed to MM annually in the United States. Dramatic improvements in survival over the past fifteen years have been fueled by the rapid introduction of new therapies and resulting changes in treatment patterns. Extended survival coupled with complex and ongoing treatment contributes to significant disruptions to daily living. Therefore, the purpose of this study was to explore the many ways that a MM diagnosis disrupts and interferes with a person’s life in the current treatment era. Methods: A cross sectional qualitative descriptive study was conducted to explore the impacts of MM diagnosis and treatment on patients’ lives in the era of novel MM treatment. Semi-structured one-hour interviews were conducted at the Duke Cancer Center with MM patients and MM clinicians to explore MM’s impact on patients’ lives. Results: Fifteen MM patients and ten MM clinicians were interviewed between September 2017 and September 2018. Themes arose around ways that a MM diagnosis and treatment had far reaching and serious impacts on patients’ lives. Four major themes emerged: ‘Impacts on Social Life and Hobbies’, Maintaining Employment’, ‘Financial Pressure’, and ‘Relationship Stress'. Conclusions: The care of MM patients has made great strides as new and more effective treatments have extended survival for many patients. Health care at its best endeavors to reduce suffering as well as extend life. This study highlights the far-reaching impacts MM has on all aspects of patients’ lives. Understanding how a myeloma diagnosis and its treatment may interfere in patients’ lives could inform the development of interventions that target management strategies to limit these negative impacts.

Pembrolizumab in men with heavily treated metastatic castration-resistant prostate cancer (mCRPC).

172 Background: Pembrolizumab is approved for patients with metastatic, microsatellite instability-high (MSI-H) or mismatch repair-deficient (dMMR) solid tumors who have progressed on prior therapy and have no satisfactory treatment options. However, very few men with PC were included in these initial studies. We evaluated the clinical activity of pembro in a cohort of men with mCRPC and their responses based on molecular genotype. Methods: We performed a retrospective, IRB-approved review of all men with mCRPC in the Duke Cancer Center who were treated with pembro in order to define the duration of therapy, time to PSA-progression, and imaging responses according to prior/concurrent therapy and by molecular subtypes. Results: We identified 51 men who received ≥1 cycle of pembro for mCRPC. Of these, 86% (44/51) had ≥3 prior lines of therapy after ADT, including abiraterone (88%), docetaxel (86%), enzalutamide (enza, 80%), and sipuleucel-T (74%). Somatic tumor sequencing was available in 18/51 men (35%). We found that 16% (8/51) had a ≥50% confirmed PSA decline with pembro, with 8% (4/51) having ≥90% PSA decline. Two of 4 had mutations in LRP1b, one of whom also had MSH2loss and was MSI-H and TMB-high; of the other 2 patients, one had no actionable mutations and the other had no genetic testing available. Fifty-nine percent (30/51) of men were treated with concurrent therapy with pembro (most commonly enza); however, all patients with PSA responses who were concurrently treated with enza had prior documented PSA progression on enza. Overall, the median time to discontinuation of treatment was 5.8 months (mo), median PSA-PFS, defined as a 25% increase in PSA from baseline, was 1.4 mo, and median OS was 6.7 mo. Among patients with ≥50% PSA decline, duration of response ranged from 3.7 to 16.3 mo with 5 patients with ongoing responses. Conclusions: In a heavily pre-treated population of men with mCRPC, pembrolizumab was associated with a ≥50% PSA decline in 16% (8/51) of men, including a dramatic ≥90% PSA response in 8% (4/51), two of whom harbored LRP1b mutations, one also with MSH2loss and a MSI-H tumor. Large prospective studies with genomic testing are needed to identify men with the greatest chance for response to immunotherapy.

Abstract 5702: Characterization of circulating tumor cells during immune checkpoint inhibition in metastatic renal cell carcinoma and malignant melanoma

Abstract Background: Although immune checkpoint inhibitors (ICIs) have shown efficacy in a range of solid tumors, there are no established circulating biomarkers able to identify early responders to treatment. Circulating tumor cells (CTCs) allow a non-invasive peripheral assessment of disease burden over time. We evaluated the prevalence of CTCs before and during treatment with ICIs. Methods: Patients were enrolled prospectively at Duke Cancer Center and UNC Lineberger Cancer Center and selected for metastatic renal cell carcinoma (mRCC) and metastatic malignant melanoma (mMM) receiving standard of care immunotherapy. Using E-selectin for slowing cell rolling and a nanoparticle dendrimer based technology for cell capture with EpCAM, HER2, and EGFR, the CapioCyte platform was used for CTC capture at baseline, during treatment, and upon disease progression. Results: We enrolled 5 subjects with mRCC and 4 subjects with mMM. Prior to treatment, subjects had a median of 293 CTCs/mL (all healthy volunteers (HVs, n=10) had &amp;lt;8 CTCs/mL). All subjects had more CTCs at baseline than HVs. One subject had CTCs rise within the first 4 weeks on ICI treatment, which corresponded to clinical disease progression. Several other subjects showed a rapid decrease in CTCs within 4 weeks but increased at the time of disease progression. In most cases of disease control, CTCs decreased by at least 50% at the 4-week timepoint and increased at time of disease progression. Conclusions: CapioCyte is a sensitive platform to detect CTCs in mRCC and mMM. Based on CTC detection, many patients had early response to ICI treatment, but rapid progression corresponding to clinical progression. This pilot data suggest that CTCs can be a valuable biomarker for monitoring the clinical benefit of cancer immunotherapies. Citation Format: Tian Zhang, SinJung Park, Daniella Runyambo, Michael J. Poellmann, Marco Reyes-Martinez, Zahra Mahbooba, Rebecca Green, Carrie Lee, Daniel J. George, Andrew J. Armstrong, Seungpyo Hong, Andrew Z. Wang. Characterization of circulating tumor cells during immune checkpoint inhibition in metastatic renal cell carcinoma and malignant melanoma [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 5702.

Clinical utility of Foundation One tissue molecular profiling in men with metastatic prostate cancer.

318 Background: In the era of precision medicine, significant effort has been placed on identifying clinically actionable molecular targets to aid in the treatment of metastatic prostate cancer (mPC). Recent data supports homologous repair and mismatch repair deficiencies to guide the use of PARP inhibitors/platinum chemotherapy or pembrolizumab, respectively. We analyzed the clinical utility of Foundation One (FO) somatic genomic profiling in men with mPC. Methods: We performed a retrospective review of men with mPC in the Duke Cancer Center who received FO testing 01/2010 - 04/2017. We asked whether FO testing identified actionable genomic lesions that led to a change in clinical practice, and if men benefited from this novel genomic matched approach to treatment. Results: We identified 77 men with FO tests. Of these, 77% (59/77) had adequate tissue for FO testing. 76% had mCRPC, 42% had &gt; 3 prior systemic therapies (enzalutamide 51%, docetaxel 39%, abiraterone 41%, sip-T 34%, radium-223 22%). The most common FO genomic alterations were: TP53 deletion/mutation (37%), TMPRSS2-ERG fusion (32%), and PTEN loss (31%). FO revealed 207 genomic alterations, classified into actionable (6), potentially actionable (44), non-actionable (126), and non-informative (31). Of the 6 patients with actionable mutations (BRCA2, ATM, PALB mutation/loss), 4 (67%) received matched olaparib therapy and 3 had PSA or prolonged radiographic stabilization, with durations of therapy of 3-19 months. Of 28 men with potentially actionable genomic findings, 3 (11%) received targeted therapies, including olaparib for a CDK12 mutation, and pembrolizumab for a PMS2 mutation and for a PD-L2 genomic gain. No responses to pembro were observed; the man with a CDK12 mutation responded to olaparib for 8 months. Overall, 42% (25/59) of evaluable men did not have a targetable mutation; 4/77 (5%) had clinical benefits from testing. Conclusions: A small but significant minority (~5%) of men with mPC appear to benefit from FO somatic tumor profiling, particularly those with homologous repair deficiencies. Larger prospective studies are needed with clinical outcomes in order to further understand the clinical utility of routine FO testing in this setting.

Expression of immune checkpoints on circulating tumor cells in men with metastatic prostate cancer (mPC).

191 Background: Most immune checkpoint inhibitors have shown limited efficacy in unselected men with mPC, and there is limited understanding about which immune checkpoints (ICs) are relevant in mPC. We evaluated ICs on the cell surface of circulating tumor cells (CTCs) in patients with mPC. Methods: Patients were enrolled prospectively at the Duke Cancer Center in three cohorts: A) mCRPC starting the novel androgen receptor inhibitors abiraterone acetate (AA) or enza with or without sipuleucel-T, B) mCRPC with disease progression after AA or enza, and C) metastatic castration sensitive PC. The Cellsearch platform was used to capture EpCAM- and CK-expressing CTCs and analyzed for PD-L1, PD-L2, B7-H3, and CTLA-4 expression at baseline, 12 weeks, and at further disease progression. Results: Through August 2017, we enrolled 4 subjects in cohort A, 7 in cohort B, and 3 in cohort C. CTCs were detectable in every cohort. At baseline, B7-H3 was the most prevalent IC on a per-patient basis (mean 96% in cohort A, and 100% in cohort B, and 88% in cohort C). PD-L1 was detected less frequently (cohort A mean 8%, cohort B mean 42%, and cohort C mean 67%), with evidence of heterogeneity of CTC PD-L1 expression between and within patients. PD-L1 was expressed on 8% of CTCs in cohort C and cohort A, as compared to 28% of CTCs in cohort B, while CTLA-4 expression was not identified in cohort C, 3% of cohort A, and 15% of cohort B. B7H3 was expressed on 68% of cohort C, 91% of cohort A, and 98% of cohort B. PD-L2 was expressed on 0-7% of CTCs overall. Conclusions: Patients with mPC can have detectable and heterogeneous ICs on CTCs, particularly PD-L1 and B7-H3, and these characteristics can be monitored over time. B7-H3 was the most prevalent IC on CTCs, regardless of disease state. Our preliminary data suggests that men with mCRPC post-enza/AA have higher levels of PD-L1 and CTLA-4 expression on their CTCs as compared with men with mHSPC and mCRPC prior to enza/AA. Patient enrollment and analysis are ongoing.

Association of neuroendocrine phenotype with platinum chemotherapy outcomes in men with metastatic prostate cancer.

e16532 Background: DNA repair defects are common in men with mCRPC, and platinum chemotherapy may have a role in selected patients. We aimed to determine whether neuroendocrine variant prostate cancer (NEPC) is associated with a greater response to platinum chemotherapy, as compared to CRPC with adenocarcinoma histology (AdenoCRPC). Methods: We conducted a retrospective cohort analysis of all patients with prostate cancer treated with platinum chemotherapy at the Duke Cancer Center between 2005-15. The primary endpoint was objective response rate (RESIST v1.1; ORR); secondary endpoints were PSA decline, progression-free (PFS) and overall survival (OS). Outcomes were compared by histologic phenotype (NEPC vs. AdenoCRPC). Results: Between 2005-2015, 73 men, including 56 with AdenoCRPC and 17 with NEPC, were treated with platinum-based chemotherapy for mCRPC. Carboplatin-docetaxel and carboplatin/cisplatin etoposide were the most common regimens. Fifteen men (21%) were M1 at diagnosis. Among NEPC patients, 3 had primary NEPC/small cell carcinoma at diagnosis, while 14 had NEPC transformation after hormonal therapy. Overall, 24% of NEPC men received prior docetaxel vs. 75% of AdenoCRPC men. Partial responses were observed in 59% in men with NEPC vs. 25% for AdenoCRPC. Primary progressive disease occurred in 24% (NEPC) vs. 48% (AdenoCRPC). PSA declines with platinum chemotherapy were more common in NEPC (median 72% decline) vs. AdenoCRPC (median 24% decline). There was no significant difference in median PFS or OS between phenotypes (NEPC PFS 5.1 mo, OS 8.5 mo; AdenoCRPC PFS 4.3 mo, OS 10.0 mo; p = NS). For second platinum chemotherapy, ORR and PFS in NEPC vs AdenoCRPC were 67% and 5.2 months vs. 14% and 4.6 months. Conclusions: Our data suggest that men with NEPC histology have a greater probability of objective response and PSA decline with platinum chemotherapy vs. men with AdenoCRPC. However, PFS and OS are similar across histologic phenotypes, indicating similar times to resistance to platinum chemotherapy. Biomarkers of platinum sensitivity are needed, and evaluation of DNA repair defects in this setting may provide a greater opportunity for precision medicine approaches to DNA damaging agents.

Vaginal Dose Is Associated With Toxicity in Image Guided Tandem Ring or Ovoid-Based Brachytherapy

To calculate vaginal doses during image guided brachytherapy with volume-based metrics and correlate with long-term vaginal toxicity. In this institutional review board-approved study, institutional databases were searched to identify women undergoing computed tomography and/or magnetic resonance-guided brachytherapy at the Duke Cancer Center from 2009 to 2015. All insertions were contoured to include the vagina as a 3-dimensional structure. All contouring was performed on computed tomography or magnetic resonance imaging and used a 0.4-cm fixed brush to outline the applicator and/or packing, expanded to include any grossly visible vagina. The surface of the cervix was specifically excluded from the contour. High-dose-rate (HDR) and low-dose-rate (LDR) doses were converted to the equivalent dose in 2-Gy fractions using an α/β of 3 for late effects. The parameters D0.1cc, D1cc, and D2cc were calculated for all insertions and summed with prior external beam therapy. Late and subacute toxicity to the vagina were determined by the Common Terminology Criteria for Adverse Events version 4.0 and compared by the median and 4th quartile doses, via the log-rank test. Univariate and multivariate hazard ratios were calculated via Cox regression. A total of 258 insertions in 62 women who underwent definitive radiation therapy including brachytherapy for cervical (n=48) and uterine cancer (n=14) were identified. Twenty HDR tandem and ovoid, 32 HDR tandem and ring, and 10 LDR tandem and ovoid insertions were contoured. The median values (interquartile ranges) for vaginal D0.1cc, D1cc, and D2cc were 157.9 (134.4-196.53) Gy, 112.6 (96.7-124.6) Gy, and 100.5 (86.8-108.4) Gy, respectively. At the 4th quartile cutoff of 108 Gy for D2cc, the rate of late grade 1 toxicity at 2 years was 61.2% (95% confidence interval [CI] 43.0%-79.4%) below 108 Gy and 83.9% (63.9%-100%) above (P=.018); grade 2 or greater toxicity was 36.2% (95% CI 15.8%-56.6%) below 108 Gy and 70.7% (95% CI 45.2%-96.2%) above (P=.004); and grade 3 or worse toxicity was 9.9% (95% CI 0.0%-23.6%) below 108 Gy and 30.0% (95% CI 4.7%-55.3%) above (P=.025). This association was maintained on multivariate analysis, independent of covariates such as applicator type, age, and dose rate. Vaginal dose was associated with all grades of vaginal toxicity. Confirmation at other sites using this methodology will be necessary to establish reproducibility; however, the integration of routine calculation of vaginal dose may be warranted.

Outpatient Palliative Care at Duke Cancer Center

Outpatient Palliative Care at Duke Cancer Center

Copayment assistance and adherence to prescription medication among patients with cancer.

57 Background: The relationship between prescription medication adherence and copay assistance is understudied and directly impacts quality of care. Methods: We conducted a cross-sectional survey study assessing patient-reported failure to take medication as prescribed (nonadherence) and application for copay assistance. Participants were enrolled between 6/2010-5/2011 from the HealthWell Foundation (a copay assistance program) and Duke Cancer Center. Eligible patients were adults receiving treatment for a solid malignancy. Nonadherence was defined as taking a less than prescribed amount of medication, not filling or partially filling a prescription, or taking medications prescribed for someone else. Adherence and receipt of copay assistance were not linked to a specific drug. Logistic regression assessed the association between medication nonadherence, copay assistance application, and financial burden. Results: Among 258 participants, 75% applied for copay assistance. 38% (n=99) reported nonadherence with medications due to cost. Compared to adherent participants, nonadherent participants were more likely to: ask their doctor for a less expensive medication than prescribed (p&lt;0.001); reduce spending on basics like food or clothing to pay for medication (p&lt;0.001); purchase an over-the-counter drug to replace a more costly prescription (p&lt;0.001); borrow/use credit to pay for medications (p&lt;0.001); and talk with doctors about treatment-related costs (p=0.014). In adjusted analyses applying for copay assistance did not change odds of nonadherence. Having a prescription drug plan (OR 6.56, 95% CI 1.69-25.53) and utilizing coping strategies (OR 2.72, 95% CI 2.03-3.65) increased odds of nonadherence; older age (OR 0.93, 95% 0.88-0.98) decreased odds of nonadherence. Conclusions: Medication nonadherence due to cost was prevalent among cancer patients whether or not they applied for copay assistance. To afford medications cancer patients adapted their lifestyles and altered their care. Future research should investigate whether underinsured patients have timely access to copay assistance programs and whether copay assistance impacts the quality of care.

Evaluation of a breast cancer survivorship clinic that uses a group medical appointment model: Patient program evaluation and financial analysis.

90 Background: Group medical appointments have been shown to improve access, health outcomes and health care utilization rates, as well as self-management skills. A new model of breast cancer survivor care was designed and piloted at Duke Cancer Center. Survivors attended the clinic together in groups of six. An interdisciplinary group visit format in the initial part of the appointment provided surveillance, education and support, as well as formation of an individualized survivorship care plan. The first hour included review of their personal care plan and a 45-minute facilitated discussion. Afterwards, individual visits with the nurse practitioner, and dietitian, physical therapist, or social worker occurred. Methods: A 22-item Likert-type questionnaire sought opinions regarding logistics and the style and function of care delivered. 122 surveys were collected. Descriptive statistics (via SPSS v19) using ANOVA type regression were accomplished. Secondly, a retrospective two-group study of clinic financial data for follow-up patients was done. Revenues from the group medical visit by the NP were compared to those seen traditionally by the MD (N=300). Review of time to third available appointment for each clinician was also recorded. Results: 122 surveys were collected with a 86% response rate. Mean scores for all questions rated at least 4.4 of 5, with the highest score given for the confidence felt in the nurse practitioner (4.93) and the lowest for the acceptability of the wait time in the breast imaging area (4.4). Overall, 98% felt the program provided quality care and 97% were likely to recommend the clinic to other breast cancer survivors. What participants liked most about the program was sharing with other survivors. Cost benefit analysis revealed that revenues and direct costs were nearly equal between delivery models. Time to third available appointment for the primary referring oncologist, dropped from 29.4 to 26.7 days, while the NPs time remained stable at 8.7 days. Conclusions: The group visit model applied to survivor care appears feasible and highly satisfactory to participants.

P4-12-15: Cancer Survivor Care: An Evaluation of a Group Visit Model of Care for Breast Cancer Survivors at Duke Cancer Center.

Abstract Background: The number of cancer survivors is growing, currently with about 2.5 million breast cancer survivors. (ACS, 2010). The Institute of Medicine report on survivor care stressed care coordination along with attention to survivor concerns as key issues in improving follow-up care. Group visits have been shown to improve access, health outcomes and health care utilization rates, as well as self-management skills. Purpose: This prospective program evaluation measured patients opinions about participation in a group visit clinic. Methods: A new model of breast cancer survivor care was designed and piloted at Duke Cancer Center. Breast cancer survivors who were three years post diagnosis attended the clinic together in groups of six. An interdisciplinary group visit format in the initial part of the appointment provided surveillance, education and support, as well as formation of an individualized survivorship care plan to be shared with the primary care provider. The first hour included review of their personal care plan and a 45-minute facilitated discussion. Afterwards, individual visits with the nurse practitioner, and dietitian, physical therapist or social worker occurred. A 22-item questionnaire designed to ascertain opinions regarding logistics and the style and function of care delivered is being administered to participants. The evaluation tool was approved by a panel of experts; pilot tested and has a reading level of 7.8. Data collection will be complete July 1, 2011. 103 surveys have been collected with a 91% response rate. Preliminary analysis shows high satisfaction with the group visit format. What participants liked most about the program was sharing with other survivors. 86% of participants indicate that they will share the survivorship care plan with their PCP. Only 10% responded that they were not sure they needed this type of follow up now and expressed that it would be more helpful immediately after finishing treatment. Final data will be presented. Barriers and facilitators to implementing this type of care model will be presented. Conclusions: The group visit model applied to a breast cancer survivor clinic appears feasible and highly satisfactory to participants. Implications for practice: Group visits can be considered one option for survivor care. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P4-12-15.

Abstract SY24-02: Development of recombinant vaccines for the prevention and therapy of human carcinomas

Abstract SY24-02: Development of recombinant vaccines for the prevention and therapy of human carcinomas