Treatment Outcomes In Patients Research Articles

Oncologic outcome of response-guided axillary treatment in patients with cN1 breast cancer after primary systemic therapy.

514 Background: In breast cancer, the majority of clinically node positive (cN1) patients are treated with primary systemic treatment (PST), with increasing rates of axillary pathologic complete response (pCR). Evidence supporting tailoring axillary treatment according to the response is growing. However, it is still debatable whether ALND is beneficial in cN1 patients with residual nodal disease and if any further axillary treatment is necessary in patients achieving pCR. In this study, we present the four-year oncologic outcome of cN1 patients undergoing either axillary radiation treatment or no axillary treatment according to the ‘Marking Axillary lymph nodes with Radioactive Iodine seeds’ (MARI)-protocol. Methods: Between 2014 and 2021, we prospectively enrolled patients with node positive breast cancer and 1 - 3 involved axillary lymph nodes on FDG-PET/CT pre-PST, who were treated according to the MARI-protocol. Patients with residual disease of the MARI node (ypN1) received axillary radiotherapy (RT), while patients with a pCR of the MARI node (ypN0) received no further axillary treatment. The primary endpoint was the axillary recurrence rate. Secondary endpoints include invasive disease free survival (iDFS) and overall survival (OS), calculated using the Kaplan-Meier method. Results: Of the 367 included patients, more than half (54%, n= 198) had hormonal receptor positive (HR+)/Human Epidermal growth factor 2 negative (HER2-) breast cancer; 59 patients (16%) had HR+/HER2+; 39 patients (11%) had HR-/HER2+ and 71 patients (19%) had triple negative (TN) subtype. Median age was 49 (IQR 41 – 56) years. 231 (63%) patients who had ypN1 received RT and 136 patients (37%) who achieved ypN0 received no further axillary treatment. Median follow up was 49 (IQR 32 – 70) months. Axillary recurrence rate was 3.5% ( n= 8) in patients with ypN1 and 0.7% ( n= 1) in patients with ypN0. Most axillary recurrences ( n= 6) occurred simultaneously with distant metastases in the ypN1 group. In patients with ypN1, the iDFS was 86% and the OS 93%; in ypN0 patients, the iDFS was 93% and the OS 98%. Conclusions: Response-guided axillary treatment in patients with limited nodal disease according to the MARI protocol is associated with favorable oncologic outcome without performing ALND’s. De-escalation can therefore be considered safe. [Table: see text]

Acute Coronary Syndrome: Treatment Strategies and Outcomes in Patients Admitted to a Tertiary Care Hospital in Palestine.

Acute coronary syndrome (ACS) is the leading cause of death worldwide despite advances in treatment and prevention measures. This study aimed to explore ACS treatment strategies (ischemia-guided vs early invasive) and risk factors among patients diagnosed with ACS in a tertiary care hospital in Palestine and to evaluate related outcomes regarding future events and standard clinical guidelines. This retrospective cohort study reviewed patient data from a Palestinian medical hospital. The study included 255 patients ≥ 18 years who were hospitalized between January 2021 and December 2021 and diagnosed with ACS. The data were analyzed using the Statistical Package for Social Science (SPSS). 71% of the participants were males. The mean age was 59.59±11.56 years. Smoking, diabetes, and hypertension were the most common risk factors. Unstable angina (UA) was the most prevalent ACS type, accounting for 43.1% (110) of cases, whereas NSTEMI accounted for 39.2% (100) and STEMI accounted for 17.6% (45) of cases. An ischemic-guided strategy approach was used in 71% (181) of the patients. Upon discharge, the most prescribed medication classes were antiplatelets (97.6%), statins (87.1%), PPIs (72.5%), and antihypertensives (71.8%). Treatment strategies were selected according to the clinical guidelines for most ACS types. ACS management in Palestine continues to evolve to overcome barriers, decrease patient mortality, and decrease hospital stay. UA and NSTEMI were the most common ACS diagnoses at admission, and the ischemic strategy was the most common modality. The findings of this study call for an increased awareness of CVD risk factors, resource availability, and adherence to clinical guidelines to improve patient outcomes and community health.

Real-world treatment patterns and clinical outcomes among patients with HR+/HER2- advanced/metastatic breast cancer receiving palbociclib in Brazil: IRIS study.

e13088 Background: Palbociclib was approved for hormone receptor-positive (HR+) and human epidermal growth factor receptor 2-negative (HER2-) advanced/metastatic breast cancer (aBC/mBC) in Brazil in 2018. Worldwide studies explore palbociclib's real-world use and outcomes; however, this data is not available for Brazilian patients. IRIS Brazil study aimed to describe demographic/clinical characteristics, treatment and clinical outcomes of adult female patients who have received palbociclib as first-line treatment for HR+/HER2- aBC/mBC in private healthcare institutions in Brazil. Methods: This retrospective descriptive study included females aged 18 years or older diagnosed with HR+/HER2- aBC/mBC and those who had received palbociclib as their initial line of therapy. The study analyzed variables such as demographics, clinical characteristics, treatment history, palbociclib combinations, and clinical outcomes. Progression-free survival (PFS) and overall survival (OS) were calculated using Kaplan-Meier estimates at 6- and 12-month time points. Results: A total of 121 patients were included in the study. The mean age was 54.4 years, and 82 (67.7%) were menopausal at diagnosis. A total of 51 patients (42.1%) were treated with palbociclib + fulvestrant, while 67 (55.8%) were treated with palbociclib + aromatase inhibitors. The majority of patients (n = 79; 65.3%) did not require any dose adjustments. Among the 40 patients (33.1%) who required dose adjustments, the main reason was adverse events/toxicity (n = 36; 90%). The PFS rates at 6 and 12 months were 78% and 60%, respectively. The OS rates at 6 and 12 months were 86% and 70%, respectively. Conclusions: Results from this initial real-world assessment of clinical outcomes in Brazil suggest that Palbociclib combinations exhibit favorable effectiveness in treating HR+/HER2- aBC/mBC disease, as measured by PFS and OS rates.

Circulating tumor DNA for recurrence monitoring following resection for pancreas adenocarcinoma.

e16365 Background: Detecting early recurrence among patients with resected pancreatic cancer may facilitate earlier treatment and better outcomes for patients with resected pancreatic ductal adenocarcinoma (PDAC). Circulating tumor DNA (ctDNA) has shown promise as a tumor-specific biomarker for PDAC but has not yet entered routine clinical use. This study aims to conduct analytical and clinical validation of Signatera ctDNA profiling to predict recurrence in patients with PDAC. Methods: A retrospective IRB-approved protocol evaluating the use of Signatera ctDNA testing among patients who underwent resection at Northwell Health during 2019-2023. The utility of ctDNA status to predict PDAC recurrence during follow-up was assessed using cox regression. Results: There were 91 ctDNA tests among 24 patients. With a median follow-up of 15 months, recurrence was observed in 38% (9/24) of patients and 8 patients died. Among patients with recurrence, most of them had positive ctDNA before showing signs of recurrence on the imaging (6/9, 66.7%) with mean lead time of 116 days, while 2 of them had positive ctDNA after recurrence and one patient never had positive ctDNA. At the time of recurrence, eight patients had elevated CA19-9, while two patients with normal CA19-9 had positive ctDNA. The median recurrence-free survival (RFS) was 23 months (95% CI, 11-not reached). Patients with detectable preoperative ctDNA had significantly decreased median RFS (14 months; 7 of 10 (70%) recurred) when compared with patients negative for ctDNA [not reached; 2/14 (14.3%) recurred; P= 0.005). In multivariable Cox model after adjusting for potential risk factors, detection of ctDNA was associated with RFS. (table). Conclusions: Signatera ctDNA profiling identified relapse earlier than imaging for most patients. These results suggest the potential for a prospective trial evaluating early treatment interventions in this deadly disease to improve survival rates. [Table: see text]

Previous radiotherapy increases the efficacy of cemiplimab in the treatment of locally advanced and metastatic cutaneous squamous cell carcinoma: a retrospective analysis

BackgroundCemiplimab, a PD-1 inhibitor approved in 2018 for patients with locally advanced or metastatic cutaneous squamous cell carcinoma (cSCC) who are ineligible for curative therapies, lacks clarity regarding the optimal patient selection despite its known efficacy. ObjectiveThis retrospective study aims to assess the real-world treatment patterns and outcomes in patients with cSCC at our institution. MethodsA retrospective analysis of consecutively treated patients with cemiplimab for cSCC was conducted. Progression-Free Survival (PFS) and Overall Survival (OS) were evaluated alongside clinical-pathologic characteristics. Results45 patients were included, of which 73.3% were male with a median age of 77 years. After 18 months of median follow-up median PFS and OS were not reached with a mean of 21.3 months ± 2.2 months and 25.3 ± 2.1 months, respectively. Univariate and multivariate analyses revealed significant correlations only between PFS and previous radiotherapy (p-values: 0.043 and 0.046, respectively).Limitations: limitations include its retrospective nature, the low number of patients analyzed and the potential for inherent biases. ConclusionsThe study reveals a significant association between prior radiotherapy and improved PFS in cemiplimab-treated cSCC, suggesting the potential for combining radiotherapy with cemiplimab. Further exploration of this combined approach is warranted.

Symptom profiles and intensive treatment outcomes in sexual minority and heterosexual patients with OCD

Sexual minority (SM) individuals appear to be at greater risk for obsessive-compulsive disorder (OCD). Despite this, little is known about OCD presentation and treatment outcomes among SM individuals. Although some research has suggested that SM individuals may be more likely to endorse unacceptable thoughts related to violence/sex/religion compared to heterosexual individuals, extant literature has neglected to examine potential differences across different SM groups, a notable limitation given the apparent differences in the types of minority stress that each group experiences and the unique health disparities affecting each group. The current study sought to address these gaps by examining potential differences in OCD symptom severity, presentation, and treatment outcomes using analysis of variance and profile analysis in a clinical sample of 1,502 cisgender patients diagnosed with OCD enrolled in intensive OCD treatment (87.5% heterosexual, 6.6% bisexual, 4.7% lesbian or gay, and 1.1% questioning). Replicating previous research, neither OCD severity nor treatment outcomes differed by sexual orientation, and findings extended previous research that no differences across SM groups were observed, either. However, contrary to previous research, there was also no evidence for unique profiles of OCD symptoms across sexual orientation groups, and questioning individuals reported significantly less severe symmetry symptoms compared to heterosexual and bisexual individuals. Findings are encouraging in that they suggest that cisgender bisexual, lesbian or gay, and questioning individuals with OCD can still benefit significantly and to the same degree as their cisgender heterosexual peers in intensive OCD treatment. Potential explanations for conflicting findings regarding symptom profiles are discussed.

Acceptability of compounded preparations – A Romanian pediatric hospital perspective

Compounded medicines are widely used, especially for pediatric patients. The aim of this study was to evaluate children’s acceptability of compounded preparations and to provide information regarding compounding practices' characteristics in a Romanian hospital setting. An observational, cross-sectional, and retrospective study was conducted in three Clinical Pediatric Departments (Emergency Clinical Hospital for Children, Cluj-Napoca). The study population comprised patients under 18 years old taking at least one compounded medication. Study data was collected mainly through an interviewer-administered questionnaire and medicine acceptability was assessed based on the children’s first reaction to the preparations using a 3-point facial hedonic scale. A total of 162 compounded medications were evaluated. A positive/negative reaction was reported for 20.83%/58.33%, 20.63%/49.21%, and 66.67%/7.41% of oral, oromucosal and cutaneous dosage forms. Although patient disapproval was recorded for various reasons, medication administration was successful in over 75% of cases. Factors such as fewer steps required for intake of a dose, capsule dosage form, no additional food/drink immediately after drug intake, medication perceived as “easy/very easy” to swallow, were correlated with a better acceptability of oral preparations. This study highlights the importance of identifying factors that can improve the acceptability of compounded preparations and, subsequently, treatment outcomes in pediatric patients.

Effectiveness of narrowband ultraviolet B monotherapy versus combination therapy with systemic agents in patients with early-stage mycosis fungoides and the association with plaque lesions.

Narrowband ultraviolet B (NB-UVB) has been recommended as first-line therapy for early-stage mycosis fungoides (MF) in international guidelines. NB-UVB can be used as monotherapy or part of a multimodality treatment regimen. There is limited evidence on the effectiveness and optimal patients of NB-UVB in combination with systemic therapies in MF. We aimed to assess the effectiveness of the combination versus NB-UVB monotherapy in early-stage MF and if plaque lesion status was related to these effects. This observational cohort study included 247 early-stage MF patients who had received NB-UVB combined with systemic therapies vs. NB-UVB monotherapy from 2009 to 2021. The primary outcome was partial or complete response. Overall response rate and median time to response were calculated. Hazard ratios (HRs) were estimated using the Cox model. In 139 plaque-stage patients, the response rate for combination therapy group was higher than that of monotherapy group (79.0%vs. 54.3%, p=0.006). The adjusted HR for combination therapy compared with NB-UVB monotherapy was 3.11 (95% CI 1.72-5.63). The combination therapy group also showed shorter time to response (4vs. 6 months, p=0.002). In 108 patch-stage patients, the response rate and time to response in two treatment groups showed no significant difference. There was therefore an observed interaction with patients' plaque lesion status for the effect size of NB-UVB combination therapy. No serious adverse events were observed. Adding systemic treatments to NB-UVB did not improve the treatment outcome of patch-stage patients, but it surpassed NB-UVB monotherapy for early-stage patients with plaques.

Real-world Treatment Sequencing and Outcomes With Cabozantinib After First-line Immune Checkpoint Inhibitor-based Combination Therapy For Patients With Advanced Renal Cell Carcinoma: CARINA Study Results

IntroductionReal-world data are limited on treatment sequencing and outcomes after first-line (1L) immune checkpoint inhibitor (CPI)-based combination treatment of advanced renal cell carcinoma (aRCC). Patients and MethodsIn this real-world, UK-based, retrospective study (CARINA; NCT04957160), data were obtained from hospital and electronic prescribing records. Patients were aged ≥ 18 years at aRCC diagnosis and had received 1L CPI–CPI or tyrosine kinase inhibitor (TKI)–CPI combination therapy before second-line (2L) therapy including cabozantinib. We describe treatment outcomes including 1L and 2L durations of treatment (DoT) and overall survival (OS). ResultsData from April 2015 to June 2022 were collected on 281 patients from nine UK centres. Median 1L DoT was 2.3 months for CPI–CPI therapy (n = 171) and 5.0 months for TKI–CPI therapy (n = 58). After 1L CPI–CPI or TKI–CPI therapy, median 2L DoT was 5.8 versus 4.2 months, respectively, for cabozantinib (n = 163), and 3.8 versus 2.4 months for other therapies (n = 118); median 2L OS was 15.2 and 15.3 months, respectively, for cabozantinib, and 14.6 and 24.2 months for other therapies. ConclusionDoT for 2L treatment was numerically better for cabozantinib than for other therapies, and after 1L CPI–CPI therapy than after 1L TKI–CPI therapy. Median OS was similar for 2L cabozantinib and other 2L therapies, and median OS for 2L cabozantinib was similar after both 1L therapy types. These results demonstrate the antitumour effect of 2L therapies, including cabozantinib, after 1L CPI-based combination treatment, regardless of whether 1L CPI–CPI or TKI–CPI therapy is used.

Impact of a prospective feedback loop aimed at reducing non-beneficial treatments in older people admitted to hospital and potentially nearing the end of life. A cluster stepped-wedge randomised controlled trial.

To investigate if a prospective feedback loop that flags older patients at risk of death can reduce non-beneficial treatment at end of life. Prospective stepped-wedge cluster randomised trial with usual care and intervention phases. Three large tertiary public hospitals in south-east Queensland, Australia. 14 clinical teams were recruited across the three hospitals. Teams were recruited based on a consistent history of admitting patients aged 75+ years, and needed a nominated lead specialist consultant. Under the care of these teams, there were 4,268 patients (median age 84years) who were potentially near the end of life and flagged at risk of non-beneficial treatment. The intervention notified clinicians of patients under their care determined as at-risk of non-beneficial treatment. There were two notification flags: a real-time notification and an email sent to clinicians about the at-risk patients at the end of each screening day. The nudge intervention ran for 16-35weeks across the three hospitals. The primary outcome was the proportion of patients with one or more intensive care unit (ICU) admissions. The secondary outcomes examined times from patients being flagged at-risk. There was no improvement in the primary outcome of reduced ICU admissions (mean probability difference [intervention minus usual care] = -0.01, 95% confidence interval -0.08 to 0.01). There were no differences for the times to death, discharge, or medical emergency call. There was a reduction in the probability of re-admission to hospital during the intervention phase (mean probability difference -0.08, 95% confidence interval -0.13 to -0.03). This nudge intervention was not sufficient to reduce the trial's non-beneficial treatment outcomes in older hospital patients. Australia New Zealand Clinical Trial Registry, ACTRN12619000675123 (registered 6 May 2019).

377P Prognostic model and treatment outcomes in elderly patients with metastatic pancreatic cancer

377P Prognostic model and treatment outcomes in elderly patients with metastatic pancreatic cancer

Effect of immune checkpoint inhibitor administration timing on survival outcomes in advanced biliary tract cancers: A single-center propensity score matching analysis.

e16186 Background: Circadian rhythms in the immune system and anti-tumor immune responses have not received adequate attention in terms of their impact on cancer immunotherapy. Recent advances in immune checkpoint inhibitors (ICIs) have marked a significant breakthrough in the treatment of advanced biliary tract cancer (BTC), but not all patients benefit from this therapy. Our study aimed to investigate whether the timing of ICI administration affects the treatment outcomes in BTC patients. Methods: We included patients with advanced BTC patients at West China Hospital of Sichuan University who received at least two ICI treatments from October 2019 to May 2023, with follow-up until December 2023. The primary outcome was overall survival (OS), with secondary outcomes including progression-free survival (PFS), objective response rate (ORR), and adverse event incidence. Propensity score matching (1:2 ratio, nearest-neighbor caliper width of 0.1) and COX regression were used to analyze the relationship between the proportion of ICI administrations after 16:30 and both OS and PFS, while the Chi-square test was used to compare the ORR and adverse event rates between groups. Results: A total of 207 patients were eligible for analysis. Before matching, 37 patients had more than 20% of their ICI administrations after 16:30, and 170 had less than 20%. After matching, 34 patients receiving more than 20% of ICIs after 16:30 were compared with 65 who did not. The former group showed significantly shorter OS (median 10 months [95%CI: 8-14 months] vs. 17 months [95%CI: 12-20 months], HR = 2.067 [95%CI: 1.226-3.485, P = 0.00645]) and PFS (median 5 months [95%CI: 4-7 months] vs. 9 months [95%CI: 8-12 months], HR = 2.093 [95%CI: 1.315-3.331, P = 0.00183]), with these results remaining robust after multivariate Cox regression analysis. No significant difference in ORR (χ^2 = 2.287, p = 0.131) was observed. Safety analysis showed no difference in the incidence of adverse events, including Grade 3/4 adverse events, immune-related adverse events, and medication discontinuation due to adverse events (all p > 0.050). Sensitivity analyses in patients receiving at least three ICI treatments revealed similar results. Conclusions: The timing of ICI administration influences the efficacy of immunotherapy in advanced biliary cancer, with administrations before 16:30 associated with better survival outcomes. Further research with larger sample sizes and prospective studies is needed to validate these findings.

Real-world first-line treatment patterns and outcomes in patients with locally advanced or metastatic urothelial carcinoma in the United States.

e23287 Background: Historically, cisplatin-containing chemotherapy has been the recommended first-line (1L) treatment for locally advanced or metastatic urothelial carcinoma (la/mUC). For those ineligible for cisplatin due to poor performance status, impaired renal function, or comorbidities, alternative choices include carboplatin-based chemotherapy and PD-1/L1 inhibitors. This study aimed to describe real-world treatment patterns and overall survival (OS) among US Medicare patients with la/mUC receiving 1L therapy. Methods: This retrospective study used Medicare fee-for-service claims data from 2015 through 2022 to identify patients diagnosed with la/mUC who received systemic treatment. Initiation of 1L therapy was the index date for study inclusion; treatment patterns and OS were assessed until end of data availability, discontinuation of health plan enrollment, or death. OS was estimated using the Kaplan–Meier approach, and a log-rank test was used to compare OS across the following 1L treatment groups: platinum-based chemotherapy (PBC; cisplatin- and carboplatin-based), non-PBC monotherapy, and PD-1/L1 inhibitor monotherapy. Hazard ratios (HRs) were estimated across groups using Cox proportional hazards models adjusting for baseline characteristics. Results: Of 13,104 patients included in this analysis, 77.5% were male, and mean (SD) age was 76.2 (7.5) years. The most commonly observed 1L treatment categories were PBC (cisplatin-based, 19.7%; carboplatin-based, 28.4%), PD-1/L1 inhibitors (34.8%), non-PBC (13.7%), and other combination therapies (2.9%). Common comorbidities included renal disease (39.9%), chronic obstructive pulmonary disease (36.1%), and diabetes (32.2%). Compared with patients in the cisplatin cohort, patients in other cohorts had higher NCI Comorbidity Index scores. Median duration of 1L treatment was 3.5 months for PD-1/L1 inhibitors, 3.2 months for carboplatin, 3.0 months for cisplatin, and 2.0 months for non-PBC. Median OS was longest with cisplatin (17.0 months; IQR: 7.8–51.9), followed by non-PBC (14.7; 5.5–39.7), carboplatin (10.5; 4.9–25.1), and PD-1/L1 inhibitors (9.4; 2.8–27.9). In the adjusted Cox model, all treatment groups had statistically significantly higher hazards of death compared with cisplatin, with an HR (95% CI) of 1.50 (1.41, 1.59; P< 0.001) for PD-1/L1 inhibitors, 1.38 (1.30, 1.46; P< 0.001) for carboplatin, and 1.11 (1.03, 1.19; P= 0.007) for non-PBC. Conclusions: In this large retrospective study of US Medicare patients from 2015–2022 with la/mUC, PBC was the most common 1L treatment, followed by PD-1/L1 inhibitors and non-PBC. While cisplatin-treated patients had longer OS than patients in other groups, treatment durations were short, and OS was generally poor across regimens. These findings highlight an unmet need for more effective 1L therapies in la/mUC.

Value of a multidisciplinary geriatric oncology committee on patient care in a community-based, academic cancer center.

e13771 Background: The heterogeneity in health and functional ability among older patients makes the management of cancer a unique challenge. The Geriatric Oncology Program at the University of Maryland Baltimore Washington Medical Center (BWMC) was created to optimize cancer management and recommendations for older patients. This study aimed to assess the benefits of the implementation of such a program at a community- based academic cancer center. Materials and Methods: We retrospectively analyzed patients aged ≥80 years presenting to the Geriatric Oncology Program between January 2017 and July 2022. A multidisciplinary team of specialists collectively reviewed each patient using geriatric-specific domains and stratified each patient into one of three management groups- Group 1: those deemed fit to receive standard oncologic care (SOC); Group 2: those recommended to receive optimization services prior to reassessment for SOC; and Group 3: those deemed to be best suited for supportive care and/ or hospice care. ANOVA, chi-square, and Kaplan-Meier analyses were used to assess patient outcomes. Results: Among 233 patients included, 76 (32.6%) received SOC (Group 1), 43 (18.5%) were optimized (Group 2), and 114 (49.0%) received supportive care or hospice referral (Group 3). There was no significant difference in sex, race, or age among all three groups. The Canadian Study of Health and Aging-Clinical Frailty Scale (CSHA-CFS) score was implemented in 2019 (n=90). Patients receiving supportive/ hospice care only had an average score of 5.8, while the averages for those in the optimization and SOC groups were 4.6 and 4.1, respectively (p=< .001). SOC patients had the longest average survival of 2.71 years compared to the optimization (2.30 years) and supportive care groups (0.93 years) (p= <0.001). 69.8% of optimized patients were deemed fit for SOC upon re-evaluation following optimization services. For all patients that underwent surgical interventions, post- operatively, 23 patients (85%) were discharged home and 4 (15%) were discharged to a rehab facility. The average survival after surgery for all patients was 3.16 years, while patients who were optimized prior to surgery had an average survival after surgery of 3.21 years. Conclusions: The present study demonstrates the need for specialized consideration of the heterogeneity that cancer diagnoses present in older individuals. The Geriatric Oncology Program at BWMC is able to maximize treatment outcomes for geriatric patients through the provision of SOC therapies and optimization services, while also minimizing unnecessary interventions on an individual patient-centric level.

Real-world treatment patterns and outcomes of patients with advanced melanoma treated with nivolumab plus relatimab.

e21501 Background: Programmed death-1 (PD-1) receptor inhibitors significantly increase survival rates for advanced melanoma, yet first-line PD-1 inhibitor therapy shows limited overall response rates (32.6%) and progression-free survival (4.6 months). Relatimab (RELA) was recently approved for the treatment of metastatic and unresectable stage III to IV melanoma in combination with nivolumab (NIVO). RELATIVITY-047 showed an ORR of 43% as a first-line treatment while RELATIVITY 020 showed an ORR of 9-12% in patients progressed on anti-PD-1 therapy. Although clinical trials have demonstrated NIVO-RELA provides benefit for patients with advanced melanoma, little is known about real-world treatment patterns and outcomes. Methods: We performed a retrospective review of all patients with stage III and IV melanoma treated with NIVO-RELA as first-(1L) or second-line or beyond (2L+) therapy at Inova Schar Cancer Institute between September 2021 to September 2023. Primary endpoints were overall response rate (ORR), complete response (CR), partial response (PR), stable disease (SD), and progression of disease (PD) which were evaluated using the RECIST v1.1 criteria. The Kaplan–Meier method was used to generate overall survival (OS) and progression free survival (PFS) median values. Results: Eighty-eight patients were followed for an average of 6.5 months following NIVO-RELA initiation. For 1L treated patients, ORR was 58% (21% PR, 37% CR). Median PFS was 11 months (95% CI 3.1-11). For 2L+ treated patients, ORR was 33% (14% PR, 19% CR). Median PFS was 9.8 months (95% CI 4.7-17.2). Subgroup analyses observed significantly different ORR between patients previously treated with versus without anti-CTLA4 therapy (29% v 44%; p = 0.017), patients treated with NIVO-RELA more than vs within 6 months from their last other therapy (50% v 27%; p = 0.004), and among patients with stage III vs stage IV disease (67% v 30%; p = 0.031) (Table 1). Conclusions: These real-world results support the use of NIVO + RELA in patients with advanced melanoma and emphasize the impressive efficacy of the drug combination in the IL and 2L+ settings compared to RELATIVITY-020 and 047. PFS and OS for 1L and 2L+ therapy with NIVO + RELA in this study aligned with or superposed results from previous trials. Further analyses with increased sample sizes and longer follow-up is warranted. [Table: see text]

Effects of L-carnitine on treatment outcomes of COVID-19 patients hospitalized in intensive care units: A double-blind randomized clinical trial

Effects of L-carnitine on treatment outcomes of COVID-19 patients hospitalized in intensive care units: A double-blind randomized clinical trial

Comparative analysis of Keynote522 treatment outcomes in Hispanic versus non-Hispanic patients with breast cancer: A single tertiary center experience.

e12661 Background: The addition of pembrolizumab to neoadjuvant chemotherapy on the Keynote522 (KN522) clinical trial, changed the standard of care for early stage triple negative breast cancer (TNBC). This regimen demonstrated longer event free survival and higher percentage of patients with pathologic complete responses (pCR). However, limited data exist on the comparative outcomes between Hispanic and non-Hispanic patients in real-world settings as this patient population was likely underrepresented on the original trial. Methods: We conducted a retrospective analysis of patients with early stage TNBC treated on KN522 regimen and undergoing surgery at a single tertiary center from July 2021 to present. Patients were stratified into Hispanic and non-Hispanic ethnicity cohorts. The primary endpoint was pCR rate, and secondary endpoints was incidence of adverse effects (AEs). Results: Among a cohort of 41 patients identified, 26 (63%) were of Hispanic and 15 (37%) were non-Hispanic. The pCR rate was 50% among Hispanic and 53% among non-Hispanic patients (p=0.83). Hispanic patients experienced higher rates of anemia (88% vs. 67%, p=0.06), fatigue (85% vs. 60%, p=0.07), skin rash (46% vs. 27%, p=0.21), and endocrine toxicities (23% vs. 13%, p=0.21). However, Hispanic patient also had fewer hospitalizations (35% vs. 47%, p=0.44), dose-modifications (12% vs. 40%, p=0.53), dose omissions (19% vs. 33%, p=0.31), and showed higher KN522 completion rates (81% vs. 53%, p=0.06). Conclusions: Our findings indicate a comparable pCR rate between Hispanic and non-Hispanic patients with early-stage TNBC receiving KN522 therapy. While Hispanic patients exhibited higher incidences of certain adverse effects, they demonstrated lower rates of hospitalizations, dose modifications, and omissions, alongside a notably higher completion rate of the KN522 regimen. These trends may be attributed to various factors such as genetic predispositions, and potentially differential physiological responses to therapy within this ethnic group. These findings underscore the importance of including minorities, such as Hispanic patients, in clinical trial populations to ensure that treatment outcomes are representative of diverse patient demographics. [Table: see text]

A survey study evaluating donor gamete utilization rates, patient satisfaction, and fertility treatment outcomes according to desired race and ethnicity

To evaluate donor gamete utilization, patient satisfaction, and fertility treatment outcomes of patients pursuing treatment with donor gametes stratified by the desired race as well as ethnicity of the gamete donor. Survey study. Clinic. Patients planning to undergo treatment using donor sperm and/or donor oocytes at a single academic fertility clinic in the Southeastern United States between 2015 and2020. None. Utilization rates of donor gametes, satisfaction with donor gamete selection, and fertility treatment outcomes stratified by race and ethnicity of patient, as well as that of their gamete donor. Four hundred fifty patients were eligible for inclusion and 170 (38%) responded to the survey. Among the respondents, 59% desired a non-Hispanic White gamete donor and 20% desired a non-Hispanic Black gamete donor. Patients seeking a non-Hispanic Black gamete donor had lower odds of using donor gametes (Odds ratio [OR], 0.13; 95% confidence interval [CI], 0.04-0.40) compared with individuals seeking a non-Hispanic White gamete donor. When evaluating satisfaction with donor gamete selection, patients seeking a non-Hispanic Black gamete donor reported lower satisfaction compared with individuals seeking a non-Hispanic White gamete donor (OR, 0.19; 95% CI, 0.09-0.43). When evaluating fertility outcomes, Non-Hispanic Black patients and those using non-Hispaninc Black gamete donors were found to have lower odds of successful conception compared with non-Hispanic White patients (OR, 0.18; 95% CI, 0.07-0.46) and individuals seeking non-Hispanic White gamete donors (OR, 0.26; 95% CI, 0.09-0.75), respectively. Patients seeking non-Hispanic Black donor gametes have lower utilization rates, less satisfaction with gamete donor selection, and lower odds of conception when compared with those seeking non-Hispanic White gamete donors. These findings highlight the need for more racial diversity within donor gamete banks, as well as within the donor pools available through agencies and fertility clinics.

Synergistic effects of RPT1G, a first-in-class small molecule NAMPT inhibitor, with venetoclax and olaparib in hematological malignancies.

e18512 Background: MultipleBCL-2 and PARP inhibitors are currently in clinical trials, or have been approved for use, in hematological malignancies and solid tumors. Venetoclax, an inhibitor of the apoptosis regulator B-cell lymphoma-2 (BCL-2), has activity in patients with chronic lymphocytic leukemia (CLL) and acute myeloid leukemia (AML). PARP inhibitors, such as Olaparib, exploit synthetic lethality in homologous recombination-deficient tumors, notably in breast and ovarian cancers. However, patients treated with BCL-2 or PARP inhibitors often face relapse and refractory disease, requiring alternative strategies to counter adaptive responses. Nicotinamide Phosphoribosyltransferase (NAMPT), the rate-limiting enzyme in the nicotinamide adenine dinucleotide (NAD+) salvage pathway, is upregulated in malignancies and plays a key role in cancer metabolism (e.g., Warburg effect). NAMPT makes nicotinamide mononucleotide which is then converted to NAD+, while PARP enzymes consume NAD+, placing NAMPT directly upstream of PARP. NAMPT overexpression is associated with Venetoclax resistance in leukemia patients, highlighting the link between NAD+, mitochondrial metabolism, and BCL-2 inhibition. Consequently, NAMPT inhibition may synergize with BCL-2 or PARP inhibitors, potentially enhancing 1st-line of treatment outcomes and re-sensitizing refractory cancer cells to BCL-2 or PARP inhibition. Methods: In this study, we investigated the combination effects of Venetoclax and Olaparib with RPT1G, a novel hyperbolic NAMPT inhibitor that simultaneously inhibits and stabilizes NAMPT in a catalytically active state. RPT1G disrupts NAMPT activity without ever turning it off completely avoiding the severe on-target toxicities seen with complete NAMPT inhibitors. Several cell lines, including OCI-AML3 and MV4;11 (AML), RS4;11 (ALL), and RL (diffuse large B-cell lymphoma) were treated with RPT1G and either Venetoclax or Olaparib to determine the degree of drug interactions. In a follow up in vivo study, we treated mice in a human xenograft model using semi-resistant MV4;11 cells with RPT1G alone or in combination with Venetoclax to measure the ability of RPT1G to enhance the effects of Venetoclax. Results: RPT1G achieves significant single-agent efficacy in leukemia and lymphoma mouse xenograft models. When RTP1G is used in combination with either Venetoclax or Olaparib significant synergy is seen across a broad range of concentrations in vitro. Consistent with in vitro synergy results, in a xenograft model of human AML, mice treated with a combination of RPT1G and Venetoclax show enhanced efficacy as compared to Venetoclax alone. Conclusions: Combination of RPT1G with either Venetoclax or Olaparib synergistically enhances killing of leukemic cells and presents as an effective strategy to improve treatment outcomes for patients with diverse malignancies.

Factors Involved in Anti-VEGF Treatment Decisions for Neovascular Age-Related Macular Degeneration: Insights from Real-World Clinical Practice.

Anti-vascular endothelial growth factor (anti-VEGF) agents are widely prescribed for the treatment of neovascular age-related macular degeneration (nAMD). Although studies have investigated patient choice of anti-VEGF agent, little is known regarding factors that influence physician preference of anti-VEGF agent for their patients. To describe physician rationale and challenges in prescribing anti-VEGF treatments for patients with nAMD. Data were drawn from the Adelphi Real World nAMD Disease Specific Programme™, a cross-sectional survey with retrospective data capture of physicians and their patients with nAMD in the United States between October 2021 and May 2022. Physicians (n = 56) reported data for up to 13 consecutively consulting patients (n = 451), including current anti-VEGF treatments used, factors affecting physicians' choice of anti-VEGF agent and treatment strategy, and restrictions on specific agents. Most physicians prefer employing a "treat-and-extend" treatment strategy, over "fixed interval" or "pro re nata" strategies. However, in routine clinical practice, "treat-and-extend" was reported for less than half of nAMD-diagnosed eyes. Top factors influencing physician choice of anti-VEGF agent and treatment strategy included maximizing clinical benefit (eg visual acuity gains and fluid control), patient convenience, and reducing out-of-pocket costs. However, physicians also reported facing substantial roadblocks in prescribing their choice of anti-VEGF agent, including restrictions on approved agents and gaps in insurance coverage. Persistent fluid was the most common physician-selected reason for switching a patient away from an anti-VEGF agent. Physicians face barriers to prescribing their preferred anti-VEGF agents in real-world healthcare settings. Overcoming these challenges may improve treatment outcomes for patients with nAMD.