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Background: Pain is a common reason for patients with cancer to seek care in the Emergency Department (ED). Many of these patients are on chronic opioids and may have developed opioid ...tolerance, which makes appropriate dosing challenging for emergency physicians. Therefore, we designed an electronic medical record (EMR) based best practice advisory (BPA) intervention to recommend appropriate opioid dosing in the ED, based on a patient’s prescription opioid use. Methods: We conducted a retrospective cohort study to evaluate our cancer pain intervention at two academic EDs from May 2020 to May 2022. Our novel BPA algorithm identified ED cancer patients who were taking prescription opioids with an EMR-calculated morphine equivalent daily dose (MEDD) of at least 100. If an ED provider ordered an opioid for one of these patients, the BPA would fire and recommend an opioid dose based on the patient’s individual MEDD. The ED provider would then have the option of accepting or cancelling the BPA. We compared outcomes based on whether patients received BPA-guided increased opioid dosing. We utilized the chi-squared test with an alpha of < 0.05 to assess the relationship between BPA-guided increased opioid dosing and pain scores, hospital admission rates and ED bounce-back rates (return visit within 7 days). Results: We identified 399 patients who met our inclusion criteria, representing 705 BPA alerts. Those patients that received increased opioid dosing were similar to those that did not, with respect to age, sex, race/ethnicity and ECOG score. Patients who received BPA-guided increased opioid dosing experienced a greater improvement in pain (72.5% vs 65.1%, p = 0.03) and were admitted less frequently (58.5% vs 63.9%, p = 0.04). However, among discharged patients, those that received increased opioid dosing bounced back to the ED more frequently (16.2% vs 7.7%, p < .01). Conclusions: This EMR-based BPA intervention was associated with improved pain scores and decreased admission rates among cancer patients visiting the ED. The same intervention, however, was associated with increased ED return visits within 7 days, suggesting that pain management strategies may need to be implemented or modified upon ED discharge to assure that patients’ symptoms are adequately managed at home.
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Background: Metaplastic breast cancer (MpBC) is a rare, aggressive, and histologically diverse subtype, which is associated with worse survival outcomes than other triple-negative breast ...cancers. Methods: This study is a single-institution retrospective analysis of 30 patients with MpBC, focused on response to therapies in the context of histologic subtype, molecular alterations, and PD-L1 expression. Patients with MpBC who received treatment at our institution consented to share clinical information with a research biorepository. Clinicopathologic and next generation sequencing (NGS) data were obtained from patients’ electronic health records. The primary outcomes are overall survival (OS) and event-free survival (EFS), and the secondary outcomes are responses to neoadjuvant therapy, tumor growth on taxane and/or anthracycline, and responses to systemic therapy in the relapsed/metastatic setting. Results: Among the 30 MpBC patients, the median age at diagnosis was 47.5 years. 86.7% were diagnosed with early-stage disease, 36.7% with squamous cell MpBC, 93.3% with triple-negative disease, and 30% with HER2-low disease. Of the patients diagnosed with early-stage disease, 88.5% received neoadjuvant systemic therapy, 96.2% underwent breast surgery, 92.3% received definitive/adjuvant radiation, and 76.9% received adjuvant systemic therapy. 61.5% of patients with localized disease experienced local and/or distant relapse. Median EFS was 14.0 months (95% CI, 10 to 20 months). Median OS was 26.5 months (95% CI, 20 to 32 months). There was no clearly superior neoadjuvant regimen based on MpBC subtype, but more patients with squamous MpBC experienced tumor growth on taxane-containing therapy compared to those with growth on anthracycline-containing regimens. In the relapsed/metastatic setting, patients with squamous cell MpBC and somatic mutations in the PI3K/Akt/mTOR pathway had prolonged partial responses to combination treatment with an anthracycline, mTOR inhibitor, and VEGF inhibitor. Median treatment duration with sacituzumab govitecan in the 1
st
or 2
nd
line metastatic setting was 1.5 months (95% CI, 1 to 4 months) before disease progression. Low tumor mutational burden was seen across all MpBC subtypes (median 2.1, 95% CI 1.6-4.0). 75% of the cases were PD-L1 positive by Immune Cell expression. There was no clear association between PD-L1 expression and response to immunotherapy-containing treatments in the neoadjuvant or relapsed/metastatic setting. Conclusions: Our findings on the presentation of MpBC correlate with other clinicopathologic studies. For squamous MpBC, we noted trends on the utility of anthracycline-containing regimens. Chemoimmunotherapy and antibody-drug conjugates have changed management of triple-negative and HER2-low breast cancer, but more prospective data are needed to determine the optimal therapeutic strategies for MpBC.
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Background: Previous studies have demonstrated that patients with cancer utilize the emergency department (ED) more frequently than the general population. Additionally, cancer ...patients are more likely to require a repeat ED visit within 7 days of a preceding ED discharge (bounce back). This may be a marker of inadequate care or missed diagnosis. We designed this study to evaluate whether there are differences in bounce-back rates among cancer patients of different races/ethnicities. Methods: We performed a retrospective cohort study to compare all cancer-related ED visits in California based on race/ethnicity using the Office of Statewide Health Planning and Development (OSHPD) database. We queried all cancer-related ED visits in 2016 among patients ≥18 years and recorded general demographics. Our outcome measures were bounce-back rate and admission rate on the second ED visit. All data were analyzed using SPSS software and descriptive statistics are reported. Results: In 2016, there were 73,465 patients with 103,523 cancer-related ED discharges that met study inclusion criteria. 18% (18,491 visits) of these visits resulted in a bounce-back (versus 13.3% in the general ED population). African American patients had the highest bounce-back rate at 19.5%, followed by Hispanics (18.9%), Non-Hispanic Whites (17.3%) and Asians (17%). We observed an inverse trend in admission rates on the bounce-back visit, with Asian patients having the highest admission rate (40.5%), followed by Non-Hispanic Whites (37.7%), Hispanics (35.1%), and African Americans (32.5%). This is in the context of an overall admission rate of 36.7%, and a high mortality rate on the bounce-back visit of 8.4%. All groups were similar with respect to age, gender, and disease burden. Conclusions: Overall, we observed that African Americans and Hispanics returned to the ED at rates above average, which may be a marker of inadequate care or misdiagnosis. Furthermore, these groups were discharged at a higher frequency on the second visit, despite the high mortality associated with a bounce-back visit. Further investigation is needed to identify actionable targets to improve the emergency cancer care of all races/ethnicities.
e13162 Background: Leptomeningeal carcinomatosis (LMC) is a rare, but deadly complication in breast cancer, with prior studies showing median overall survival (OS) of 15 weeks. There is a paucity of ...data on histologic and receptor subtype-specific survival, and there is no standard of care currently for treatment of LMC in breast cancer. We reviewed the outcomes of a contemporary cohort of breast cancer patients (pts) with LMC. Methods: This is a single-institution retrospective analysis of 38 female breast cancer pts diagnosed with LMC between 2016-2023, based on radiographic features and/or positive cerebrospinal fluid (CSF) cytology or CSF circulating tumor cells (CTCs). Patients consented to share information with a research biorepository, and we conducted a chart review of their clinical features and OS with LMC. Results: 25 pts (65.8%) had invasive ductal carcinoma (IDC), 7 pts (18.4%) had invasive lobular carcinoma (ILC), 4 (10.5%) had metaplastic carcinoma, and 2 (5.3%) had mixed IDC/ILC. 22 pts (57.9%) had triple-negative breast cancer (TNBC), 12 (31.6%) had estrogen receptor positive (ER+)/human epidermal growth factor receptor 2 negative (HER2-), and 4 (10.5%) had HER2+ disease. Median age at LMC diagnosis was 50 years. Median time between Stage IV and LMC diagnosis was 11 months. Pts received a median of 2 lines of systemic therapy for metastatic disease prior to LMC diagnosis. 11 pts (28.9%) had parenchymal brain metastasis prior to LMC diagnosis. 32 pts (84.2%) had signs of LMC on Magnetic Resonance Imaging of the brain and/or spine at diagnosis. 25 pts underwent CSF cytology and 13 pts underwent CSF CTC evaluation at LMC diagnosis; 14/25 pts (56%) had positive CSF cytology and 10/13 pts (76.9%) had detectable CSF CTCs. 21 pts (55.3%) underwent whole-brain radiotherapy, and 2 pts (5.3%) received proton craniospinal irradiation. 21 pts (55.3%) received IT therapy. 27 pts (71.1%) received at least 1 line of systemic therapy post-LMC diagnosis. Median OS between LMC diagnosis and death or last oncology follow up for the entire cohort was 5 months (range 0-57 months, 95% CI 3.0-8.0). There was a significant difference in median OS with LMC by receptor subtype: TNBC 3.5 months, ER+/HER2- 8 months, and HER2+ 23 months (p=0.0047). Two HER2+ pts survived ≥ 3 years post-LMC diagnosis with anti-HER2 antibody-drug conjugates and tyrosine kinase inhibitors +/- stereotactic radiosurgery (SRS) to parenchymal brain metastases. Amongst 9 pts with ER+/HER2-low disease, longer survival with LMC (≥ 16 months) was observed with trastuzumab deruxtecan, IT topotecan +/- IT trastuzumab, and SRS to parenchymal brain metastases. Conclusions: This study highlights heterogeneity in outcomes amongst breast cancer pts with LMC by receptor subtype, as well as improvement in outcomes for selected pts treated with novel therapeutics and a multidisciplinary approach. Larger prospective studies are needed to inform treatment paradigms for LMC.
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Background: Effective cancer screening leads to a substantial increase in the detection of earlier stages of cancer, while decreasing the incidence of later stage cancer diagnoses. ...Timely screening programs are critical in reducing cancer-related mortality in both breast and colorectal cancer by detecting tumors at an early, curable stage. The COVID-19 pandemic resulted in the postponement or cancellation of many screening procedures, due to both patient fears of exposures within the healthcare system as well as the cancellation of some elective procedures. We sought to identify how the COVID-19 pandemic has impacted the incidence of early and late stage breast and colorectal cancer diagnoses at our institution. Methods: We examined staging for all patients presenting to UCSD at first presentation for a new diagnosis of malignancy or second opinion in 2019 and 2020. Treating clinicians determined the stage at presentation for all patients using an AJCC staging module (8
th
edition) in the electronic medical record (Epic). We compared stage distribution at presentation in 2019 vs 2020, both for cancers overall and for colorectal and breast cancer, because these cancers are frequently detected by screening. Results: Total numbers of new patient visits for malignancy were similar in 2019 and 2020 (1894 vs 1915 pts), and stage distribution for all cancer patients was similar (stage I 32% in 2019 vs 29% in 2020; stage IV 26% in both 2019 and 2020). For patients with breast cancer, we saw a lower number of patients presenting with stage I disease (64% in 2019 vs 51% in 2020) and a higher number presenting with stage IV (2% vs 6%). Similar findings were seen in colorectal cancer (stage I: 22% vs 16%; stage IV: 6% vs 18%). Conclusions: Since the COVID-19 pandemic, there has been an increase in incidence of late stage presentation of colorectal and breast cancer, corresponding with a decrease in early stage presentation of these cancers at our institution. Cancer screening is integral to cancer prevention and control, specifically in colorectal and breast cancers which are often detected by screening, and the disruption of screening services has had a significant impact on our patients. We plan to continue following these numbers closely, and will present data from the first half of 2021 as it becomes available.
10600 Background: Germline genetic variation influences immune activity and risk of autoimmunity, and has been hypothesized to play a role in response to cancer therapeutics and survival. Prior ...studies of breast cancer have reported associations between genetic variation in thyroid autoimmunity and overall survival (OS). Here, we aim to investigate the association between a polygenic risk score for hypothyroidism (PRS-H) and response to therapy in women with early-stage breast cancer, and hypothesize that high PRS-H will be associated with better treatment response and survival. Methods: This study includes 1,368 women aged 18 years and above with stage II-III breast cancer of size > 2.5cm by clinical exam, with germline data available. It is an approved biomarker analysis of the I-SPY 2 trial, which is a phase II, adaptive, randomized platform trial across multiple sites studying novel cancer therapeutics across multiple arms for use as neoadjuvant chemotherapy for early-stage breast cancer. The outcome of survival is defined as alive at the most recent follow-up. Using the Cox proportional hazards model, we evaluate the association between a previously published PRS-H and overall survival. Models are adjusted for age at screening, immunotherapy status, and five principal components. Results: Among 1,368 early-stage breast cancer women, 33% (n=447) had pCR, and 85% (n=1,157) were alive at the last follow-up. Additionally, 16% (n=219) of women received immunotherapy. We observe a significant association between PRS-H and OS (HR = 0.78, 95% CI 0.66-0.92, p=0.004). Individuals in the top 10th percentile of the PRS-H (highest genetic risk) have improved survival (log rank p=0.04). Conclusions: Germline genetic variation in thyroid autoimmunity proclivity is associated with improved overall survival in our cohort of women with early-stage breast cancer receiving neoadjuvant chemotherapy. Our findings suggest that the genetic risk for autoimmunity may be important for long-term survival. We will expand this analysis to include the entire I SPY 2 population when all patients have completed genotyping. We plan to further characterize the role of germline autoimmunity profiles and survival. Clinical trial information: NCT01042379 .
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Background: The I-SPY2 Trial evaluates multiple investigative agents in neoadjuvant breast cancer therapy with the primary endpoint of estimated pathologic complete response (pCR) rate. As a ...platform phase 2 trial it utilizes an adaptive design to compare new regimens with control chemotherapy (weekly paclitaxel followed by AC). Methods: Specific regimens are assigned based on clinically relevant signatures, including triple negative breast cancer (TNBC). Drug regimens graduate from the trial when the predicted pCR rate in any signature meets the pre-specified threshold of 85% probability of success in a hypothetical 300-patient, 1:1 randomized, phase 3 trial. The strong correlation between pCR rate and event free survival has been reported. To establish the benefit of administering investigational agents in combination with control weekly paclitaxel x 12 in TNBC, we report estimated pCR rates for the first 7 investigational agents. Results: TNBC accounted for 37% (363/987) of enrolled patients. Only veliparib and carboplatin (VC) and pembrolizumab (Pembro) met the graduation criteria for TNBC. However, compared to control chemotherapy, each drug tested in TNBC resulted in a numerically superior pCR rate compared to control. These findings imply that stratification of TNBC by response-predictive biomarkers may lead to improved pCR rates. For example, we have used gene expression profiling to further refine TNBC classification into Immune enhanced (Immune+), Immune-/DNA Repair Deficient (DRD)+, and Immune-/DRD- classes. TNBC identified as immune enhanced (63%) have an 89% pCR rate to pembrolizumab, while VC is less effective with pCR rate of 71%. Similarly, Immune-/DRD+ (11%) identifies TNBCs with a 80% pCR rate to VC, while pembrolizumab’s pCR rate in this group is only 33%. For tumors that are neither immune enhanced or DRD-positive (Immune-/DRD-; 25%) show numerically improved pCR rates for neratinib (20%), MK2206 (25%), ganitumab (24%), and ganetespib (22%) compared to control (12%). pCR rates for VC (10%) and pembrolizumab (20%) in this group were similar to drugs that did not graduate. For TNBC, many agents in I-SPY2 showed numerically improved pCR rates compared to conventional chemotherapy even when they did not meet our specified definition of graduation. Conclusions: Further refinement of TNBC signatures should yield improved therapeutic strategies while also sparing women unnecessary systemic therapy. Clinical trial information: NCT01042379. Table: see text
LBA501 Background: I-SPY2.2 is a multicenter phase 2 platform sequential multiple assignment randomized trial (SMART) in the neoadjuvant breast cancer setting that evaluates novel experimental ...regimens as first in a sequence (Block A) followed by standard chemo/targeted therapies (Blocks B/C) if indicated. The goal is to achieve a pCR after novel targeted agents alone or in sequence with standard therapies, with the optimal therapy assigned based on the tumor response predictive subtype (RPS). RPS incorporates expression-based immune, DNA repair deficiency (DRD), and luminal signatures with hormone receptor (HR) and HER2 status to subset patients into 6 subtypes: S1: HR+HER2-Immune-DRD-; S2: HR-HER2-Immune-DRD-; S3: HER2-Immune+; S4: HER2-Immune-DRD+; S5: HER2+/non-Luminal; S6: HER2+/Luminal. Methods: RPS S1, S2, S3, and S4 were eligible for assignment to Dato+Durva in Block A. Patients were followed by MRI during treatment (at 3, 6, and 12 weeks after start of Blocks A and B). Predicted responders by MRI and biopsy at the end of Block A or B have the option of going to surgery early; otherwise, they proceed to next treatment Block (B +/- C). Randomization to Block B includes a taxane-based regimen specific to the RPS, and options include S1: paclitaxel; S2 and S3: paclitaxel + carboplatin + pembrolizumab; S4: paclitaxel + carboplatin vs. paclitaxel + carboplatin + pembrolizumab. Patients who did not go to surgery after Block B proceeded to Block C (AC or AC + Pembrolizumab if HR-HER2-). The primary endpoint is pCR. Efficacy is evaluated within each RPS and HR+HER2- and HR-HER2- signatures. To estimate the arm's efficacy as a stand-alone therapy, we use a Bayesian covariate-adjusted model to estimate the pCR rate and compare the posterior distribution to a subtype-specific fixed threshold. This model uses pCR data when available and MRI data when pCR is not. To estimate pCR rate in the context of a multi-decision treatment regimen, we use a Bayesian model based on if and when a pCR occurred in the trial. The posterior is compared to a subtype-specific dynamic control generated from historical I-SPY data. Results: 106 patients were randomly assigned to the Dato+Durva arm between September 2022 and August 2023. The results for Dato+Durva as a stand-alone therapy are summarized in Table. After completion of Block A, 36 patients proceeded to surgery without completing Blocks B/C. Conclusions: Dato+Durva meets threshold for graduation within the RPS S3 subtype based on estimated pCR rate of 72% and warrants further investigation in a larger randomized controlled trial. Clinical trial information: NCT01042379 . Table: see text
584 Background: I-SPY2 was the first randomized trial to demonstrate an improvement in pCR and EFS when Immune Checkpoint Inhibitors (ICI) were added to standard neoadjuvant chemotherapy. This ...finding was validated in the phase 3 KEYNOTE 522 trial for triple-negative breast cancer, leading to approval of pembrolizumab (pembro) in this setting. ICIs add the risk of immune-related adverse events (irAEs); while most irAEs are reversible, endocrinopathies appear to persist. Higher rates of adrenal insufficiency (AI), either from primary adrenalitis or hypophysitis, have been reported with ICI-based therapy (tx) in early breast cancer (EBC) compared to advanced disease. Here we describe the incidence and time of onset of AI with ICI-based tx in I-SPY2. Methods: I-SPY2 is a multicenter, phase 2 trial using response-adaptive randomization within biomarker subtypes defined by hormone receptor, HER2, and MammaPrint status to evaluate novel agents in the neoadjuvant setting in patients (pts) with high-risk EBC. Treatment included weekly paclitaxel (T) plus ICI-based tx x 4 cycles, followed by doxorubicin/cyclophosphamide (AC) every 2-3 weeks x 4. 6 completed investigational arms included ICIs: T+pembro x 4, T+pembro x 8 (+/- AC), T+pembro+SD101 (TLR9 agonist), T+durvalumab+olaparib, T+cemiplimab (cemi), and T+cemi+REGN3767 (anti-LAG-3). AI diagnoses were made by treating providers with review from two board certified endocrinologists. AI was defined as AM serum cortisol level < 3 mcg/dl in absence of recent glucocorticoid treatment. If ACTH was low or normal, pt was dx with hypophysitis; if ACTH was elevated, pt was dx with primary AI. Results: 442 pts in I-SPY2 received ICI-based tx; 11.8% (n=52) developed AI (primary+hypophysitis). Mean age of pts who developed AI was 47.3 vs 48.6 yrs in those who did not (p=0.44). Incidence of AI was highest in arms with dual immune modulation (18.1%) as compared to single ICI tx (8.5%). Median time to onset varied by arm, ranging from 92-204 days from first ICI dose. While some cases occurred during ICI tx (13.5%), the majority occurred between 12-24 wks after tx initiation, with 21.2% diagnosed after completion of all tx. The majority (94.2%) of pts with AI were symptomatic; the most common presenting symptoms included fatigue (59.6%), nausea (48.1%), and vomiting (34.6%). All pts with AI remain on glucocorticoid replacement tx. Conclusions: The incidence of AI in EBC is higher than has previously been reported in advanced disease, with higher rates observed in those tx with dual immune modulation. No correlation was observed with age; correlation of AI with response predictive subtype and other clinicopathologic features is ongoing and will be presented. Given the high incidence of AI in EBC, close monitoring in the peri/postoperative setting and education of pts and providers is critical, as risk persists even after completion of tx. Work to identify risk factors for AI is ongoing. Clinical trial information: NCT01042379 .
582 Background: Uncommon histologies are over-represented among high-risk breast cancer (BC) and denote an area with limited trial data and of significant unmet medical need. To better understand ...trial outcomes in this group and identify signals of tumor responsiveness, we report pathologic complete response (pCR) and early event-free survival (EFS) by disease subtype in the I-SPY2 trial. Additionally, the I-SPY2 trial currently utilizes a combination of tumor molecular signature and receptor status to determine response predictive subtype (RPS) first developed from 987 I-SPY2 patients (1). We report disease response rates for those who received what is now known to be optimal RPS guided therapy. Methods: The I-SPY2 platform trial tests novel agents given neo-adjuvantly with a chemotherapy backbone in high-risk BC (HER2 positive, triple negative and high molecular risk estrogen receptor positive BC). Histologic images of research biopsies, local biopsy and surgical pathology reports were reviewed centrally by I-SPY pathologists. Receptor subtype distribution and pCR rates were summarized. EFS was estimated using the Kaplan Meier method. Association between pCR and EFS was evaluated using the Cox proportional hazard model with significance assessed by the log rank test. Results: 144/2118 (7%) of I-SPY2 participants were identified with metaplastic (60), lobular (55), mucinous (9), micropapillary (8), neuroendocrine (4) and other (8) BCs. Tumor receptor status, pCR rate and EFS by tumor type are shown in the Table. For the full cohort, pCR was associated with better EFS (hazard ratio (95% CI): 0.12 (0.02 - 0.88), p = 0.01). Within metaplastic (metapBC) 11/32 (34%) and 5/28 (18%) patients had a pCR with or without checkpoint blockade, respectively. By RPS group, 9 of 18 (50%) (13 metapBC, 3 other, 2 lobular) in the HER2-Immune+ group who received RPS optimized therapy had a pCR. In this group 6/13 (46%) with metapBC had a pCR. In the HER2+ driven RPS groups, pCR rate in the HER+HER2orBasal was 88% (7/8) and 0% (0/3) in the HER2+Luminal. Conclusions: High pCR rates observed in metapBC and other among subsets of often difficult to treat BC subtypes support novel approaches and provide a roadmap for future study of uncommon BCs. Outcomes were improved when therapy matched RPS vulnerabilities. Participants presenting with uncommon BC subtypes will be prospectively identified in the I-SPY2.2 trial to further develop effective approaches for this group. 1. Wolf et al, Cancer Cell 2022. Clinical trial information: NCT01042379 . Table: see text
