Clinical Trial Criteria Research Articles

Evolution of Eligibility Criteria in Inflammatory Bowel Disease Clinical Trials: A Clinical Trial Databank Analysis.

Eligibility criteria in clinical trials have been criticised for being overly restrictive without clinical justification. We aimed to investigate the types, evolution, and current status of eligibility criteria in clinical trials for inflammatory bowel diseases (IBD). We performed a clinical trial databank search on clinicaltrials.gov, and included all Phase 3 placebo-controlled randomised-controlled trials (RCTs) investigating biologics or small molecules as induction therapy for moderate-to-severe Crohn's disease (CD) and ulcerative colitis (UC). Eligibility criteria were analysed both quantitatively and qualitatively. Fifty-nine RCTs were identified between the year 2000 and 2022 (30 for CD and 29 for UC). The median (interquartile range) number of eligibility criteria was 44 (38-49), and did not significantly change over the studied time period (p=0.26). Qualitative analysis showed that common patient populations, such as older patients, therapy refractory patients, patients with comorbidities, prior malignancies, unclassified IBD type, ulcerative proctitis, stricturing and fistulizing CD, as well as patients with an ostomy, were often excluded. Heterogeneity in eligibility criteria across the different IBD clinical trials was found, such as for disease activity measurement, dosage of concomitant medication, wash-out period of advanced therapies, and laboratory tests. The median number of eligibility criteria for IBD RCTs did not significantly change over time. The eligibility criteria are however restrictive and complex, limiting the generalisability of efficacy and safety outcomes in daily practice when drugs are approved. Future research is needed to investigate the impact of broadening eligibility criteria to better encompass real-world practice.

PNEUMATIC RETINOPEXY FOR GIANT RETINAL TEAR ASSOCIATED RETINAL DETACHMENT: A Retrospective Cohort Study

Purpose: To report the technique and long-term outcomes of patients with giant retinal tear associated retinal detachment (GRT-RD) treated with pneumatic retinopexy (PnR). Methods: Retrospective cohort study. All patients presenting with GRT-RD with tears in the superior ten-clock hours who underwent primary PnR were included in this study. Results: 31 patients were included in the study. 61.2% (19/31) achieved PARR with PnR at 3 months and 58.0% (18/31) at the final follow-up. Patients included in this study had a median follow-up of 24 months (interquartile range 46.5). The absence of retinal tears elsewhere at baseline was associated with a final PARR of 80% (16/20) (p= 0.007). Thirteen eyes required PPV after a failed PnR. Two eyes required the intraoperative use of perfluorocarbon liquids (PFCL). No eyes required silicone oil (SO). Visual acuity improved significantly from baseline to the last follow-up. Final anatomic reattachment rate was 100% (31/31). Conclusion: For selected cases of GRT-RDs affecting the superior ten-clock hours, PnR could be a possible treatment option when patients consent to extra visits and the surgeon has substantial expertise. When lacking this extensive experience and comfort with PnR, PPV remains the treatment that is most likely to result in a primary anatomic reattachment. While this study provides guidance on PnR technique for GRT-RDs, it is essential to note that the reported PARR may be contingent on the expertise of the surgeon/center, and the authors recommend that those new to PnR first gain substantial experience in cases meeting clinical trial criteria.

Disseminated intravascular coagulation is an underestimated but fatal adverse event associated with blinatumomab therapy: A pharmacovigilance analysis of FAERS.

Hematologic adverse events (AEs) are common and serious toxicities in patients with hematologic malignancies undergoing blinatumomab therapy. However, restrictive selection criteria in pivotal clinical trials can lead to an underestimation of rare but fatal toxicities. In this study, we systematically analyzed hematologic AEs associated with blinatumomab using the Food and Drug Administration Adverse Event Reporting System (FAERS) from October 2014 to December 2023. Disproportionate analysis was performed to identify overreported AEs, with a reporting odds ratio (ROR), and a lower bound of the 95% confidence interval (ROR025) exceeding one considered significant. Additionally, adjusted mortality rates and risk ratios (RR) of the top 10 reported hematologic AEs were calculated using a logistic regression model. Among 4745 blinatumomab-related cases, 418 (8.81%) involved hematologic AEs. We identified 22 significantly overreporting hematologic AEs compared to the full database, with myelosuppression (n = 39 [9.33%], ROR025 = 8.04), disseminated intravascular coagulation (DIC, n = 31 [7.42%], ROR025 = 15.14), and bone marrow failure (n = 14 [3.35%], ROR025 = 3.41) notably underestimated in clinical trials. DIC resulted in a substantial mortality rate of 45.16%. Finally, DIC was found to be independently associated with death in a multivariable logistic regression analysis (RR = 2.47 [95% CI: 1.11-3.83]). These findings could aid clinicians in the early detection of these rarely reported but fatal hematologic AEs, thereby reducing the risk of severe toxicities in blinatumomab recipients.

Unnecessary exclusion: Eligibility criteria in gynecologic oncology interventional clinical trials impair access to trials

Unnecessary exclusion: Eligibility criteria in gynecologic oncology interventional clinical trials impair access to trials

Complex system modelling reveals oxalate homeostasis is driven by diverse oxalate-degrading bacteria.

Decades of research have made clear that host-associated microbiomes touch all facets of health. However, effective therapies that target the microbiome have been elusive given its inherent complexity. Here, we experimentally examined diet-microbe-host interactions through a complex systems framework, centered on dietary oxalate. Using multiple, independent molecular, animal, and in vitro experimental models, we found that microbiome composition influenced multiple oxalate-microbe-host interfaces. Importantly, administration of the oxalate-degrading specialist, Oxalobacter formigenes, was only effective against a poor oxalate-degrading microbiota background and gives critical new insights into why clinical intervention trials with this species exhibit variable outcomes. Data suggest that, while heterogeneity in the microbiome impacts multiple diet-host-microbe interfaces, metabolic redundancy among diverse microorganisms in specific diet-microbe axes is a critical variable that may impact the efficacy of bacteriotherapies, which can help guide patient and probiotic selection criteria in probiotic clinical trials.

CriteriaMapper: establishing the automatic identification of clinical trial cohorts from electronic health records by matching normalized eligibility criteria and patient clinical characteristics

The use of electronic health records (EHRs) holds the potential to enhance clinical trial activities. However, the identification of eligible patients within EHRs presents considerable challenges. We aimed to develop a CriteriaMapper system for phenotyping eligibility criteria, enabling the identification of patients from EHRs with clinical characteristics that match those criteria. We utilized clinical trial eligibility criteria and patient EHRs from the Mount Sinai Database. The CriteriaMapper system was developed to normalize the criteria using national standard terminologies and in-house databases, facilitating computability and queryability to bridge clinical trial criteria and EHRs. The system employed rule-based pattern recognition and manual annotation. Our system normalized 367 out of 640 unique eligibility criteria attributes, covering various medical conditions including non-small cell lung cancer, small cell lung cancer, prostate cancer, breast cancer, multiple myeloma, ulcerative colitis, Crohn’s disease, non-alcoholic steatohepatitis, and sickle cell anemia. About 174 criteria were encoded with standard terminologies and 193 were normalized using the in-house reference tables. The agreement between automated and manual normalization was high (Cohen’s Kappa = 0.82), and patient matching demonstrated a 0.94 F1 score. Our system has proven effective on EHRs from multiple institutions, showing broad applicability and promising improved clinical trial processes, leading to better patient selection, and enhanced clinical research outcomes.

Impact of treat and extend criteria on proportions that can be extended after loading phase of 2 mg aflibercept therapy for neovascular age related macular degeneration: PRECISE Report 5.

To study the impact of definitions of various treatment extension criteria on the proportion of patients who could be extended at their first visit after the loading phase of 2 mg aflibercept therapy for neovascular age related macular degeneration (nAMD). Patients with nAMD initiated on the loading phase of three intravitreal doses of 2 mg aflibercept in routine clinical practice were recruited from December 2019 to August 2021. The response to the loading phase was assessed at approximately 8 weeks post-loading (up to 140 days from first injection) based on different definitions of response. The proportion of patients that qualify for interval extension based on different clinical trial criteria was also evaluated. A total of 722 patients with visual acuity (VA) and optical coherence tomography (OCT) scans done at all 4 visits were included. Of these 32.4% of eyes responded with complete macular fluid resolution after the first injection with no recurrence through the loading phase (super-responders) while 26.9% had persistent macular fluid in all 4 visits (true non-responders). The rest were considered suboptimal responders. Change in VA showed marked variations within each of these categories of fluid resolution. For extension of next treatment interval, if presence of any macular fluid at the post-loading visit is the only criteria considered, about 50% could be extended to 8 weeks. If both VA worsening by ≥5 letters and a > 25 μm increase in central sub-field thickness (CST)are considered, 90% will be eligible for interval extension. Clinical trial designs and pre-defined treatment extension/shortening criteria determine the proportion of patients requiring treatment in the post-loading visit. The short and long-term impact of interval extension immediate post-loading on visual outcome in clinical practice is unknown.

Projected Annual Lecanemab Treatment Eligibility in an Irish Regional Specialist Memory Clinic.

The advent of Disease Modifying Therapies (DMTs) for the treatment of Alzheimer's Disease (AD) has the potential to transform the lives of those with early AD. Timely identification of eligible patients is needed to ensure treatments are delivered during a narrow window of therapeutic opportunity. Appropriate clinical service design will hinge on improved understanding of future demands, thus there is a pressing need to investigate patient eligibility in real world clinical cohorts. The primary aim of this study is to assess the eligibility by appropriate use criteria (AUC) for lecanemab therapy in a real-world, undifferentiated clinical patient cohort attending a Regional Specialist Memory Clinic (RSMC), with the secondary aims of determining the proportion of patients with biomarker positive Alzheimer's Disease (AD) who would be eligible for lecanemab therapy by AUC. Clinical trial eligibility criteria were also applied to both groups and discrepancies that exist between eligibility rates explored. A retrospective cohort study of all new patients attending a RSMC from 1st January 2022 to 31st December 2022 was conducted. Data collected included demographic details, outcomes of diagnostic assessments and comorbidities. MRI images, where indicated, were reviewed. Amyloid positivity was defined as either Amyloid and Tau positive (A+T+) or Amyloid positive with a positive P-Tau/Ab42 ratio on cerebrospinal fluid (CSF) testing. Appropriate use criteria (AUC) and clinical trial criteria for lecanemab were applied. Proportion of eligible patients was calculated. Eleven (5.9%) of 188 new patient attenders were eligible (average age 66.7years [SD 8.9], 63.6% female) by AUC, with 26.2% of patients with biomarker positive Alzheimer's Disease eligible for lecanemab therapy. The most common reason for exclusion was a lack of biomarker confirmation of AD pathology followed by cognitive ineligibility (based on defined cognitive testing cut-offs) at the time of referral and/or initial assessment. Only 40.4% of patients had CSF testing for AD biomarkers while almost 20% of the patients with biomarker positive AD were excluded due to lack of a screening MRI in the previous 12months. In this study, the potential eligibility rate by AUC of the entire patient cohort (5.9%) was limited by the small proportion of patients who had CSF testing for AD biomarkers. So while disease-modification with Lecanemab is a welcome therapeutic advance, although only a small proportion of people currently attending specialist services will be eligible. Successful delivery of DMTs will require significant resource allocation and optimisation of referral pathways to facilitate early identification of potentially eligible patients.

Implications of the 2022 lung function update and GLI global reference equations among patients with interstitial lung disease

BackgroundLung function testing remains a cornerstone in the assessment and management of interstitial lung disease (ILD) patients. The clinical implications of the Global Lung function Initiative (GLI) reference equations and...

Ensuring the strict and accurate adherence to inclusion criteria in clinical trials for AMD is crucial.

Ensuring the strict and accurate adherence to inclusion criteria in clinical trials for AMD is crucial.

Evaluating the impact of laboratory-based eligibility criteria by race/ethnicity in first-line clinical trials of DLBCL

AbstractUnderrepresentation of racial and ethnic subgroups in cancer clinical trials remains a persistent challenge. Restrictive clinical trial eligibility criteria have been shown to exacerbate this problem. We previously identified that up to 24% of patients treated with standard immunochemotherapy would have been excluded from recent first-line trials in diffuse large B-cell lymphoma (DLBCL) based on 5 laboratory-based criteria. These ineligible patients had worse clinical outcomes and increased deaths related to lymphoma progression, suggesting the potential exclusion of patients who could have benefited most from the novel therapies being evaluated. Using data from the prospectively enrolled Lymphoma Epidemiology Outcomes cohort study, with demographics broadly similar to the US patients diagnosed with lymphoma, we evaluated the impact of laboratory eligibility criteria from recent first-line DLBCL trials across various racial and ethnic backgrounds. There were significant differences in the baseline laboratory values by race/ethnicity with Black/African American (AA) patients having the lowest mean hemoglobin and highest creatinine clearance. Based on recent clinical trial eligibility criteria, AA and Hispanic patients had higher rates of laboratory-based ineligibility than non-Hispanic White patients. The largest gap in the clinical outcomes between eligible and noneligible patients was noted within AA patients with an overall survival hazard ratio based on POLARIX clinical trial criteria of 4.09 (95% confidence interval, 1.83-9.14). A thoughtful approach to the utility of each criterion and cutoffs for eligibility needs to be evaluated in the context of its differential impact across various racial/ethnic groups.

Unravelling the complexity of ventilator-associated pneumonia: a systematic methodological literature review of diagnostic criteria and definitions used in clinical research

BackgroundVentilator-associated pneumonia (VAP) is a prevalent and grave hospital-acquired infection that affects mechanically ventilated patients. Diverse diagnostic criteria can significantly affect VAP research by complicating the identification and management of the condition, which may also impact clinical management.ObjectivesWe conducted this review to assess the diagnostic criteria and the definitions of the term “ventilator-associated” used in randomised controlled trials (RCTs) of VAP management.Search methodsBased on the protocol (PROSPERO 2019 CRD42019147411), we conducted a systematic search on MEDLINE/PubMed and Cochrane CENTRAL for RCTs, published or registered between 2010 and 2024.Selection criteriaWe included completed and ongoing RCTs that assessed pharmacological or non-pharmacological interventions in adults with VAP.Data collection and synthesisData were collected using a tested extraction sheet, as endorsed by the Cochrane Collaboration. After cross-checking, data were summarised in a narrative and tabular form.ResultsIn total, 7,173 records were identified through the literature search. Following the exclusion of records that did not meet the eligibility criteria, 119 studies were included. Diagnostic criteria were provided in 51.2% of studies, and the term “ventilator-associated” was defined in 52.1% of studies. The most frequently included diagnostic criteria were pulmonary infiltrates (96.7%), fever (86.9%), hypothermia (49.1%), sputum (70.5%), and hypoxia (32.8%). The different criteria were used in 38 combinations across studies. The term “ventilator-associated” was defined in nine different ways.ConclusionsWhen provided, diagnostic criteria and definitions of VAP in RCTs display notable variability. Continuous efforts to harmonise VAP diagnostic criteria in future clinical trials are crucial to improve quality of care, enable accurate epidemiological assessments, and guide effective antimicrobial stewardship.

Recommendations for broadening eligibility criteria in esophagus cancer clinical trials: the mortality disparity of esophagus cancer as a first or second primary malignancy.

Esophagus cancer as a second primary malignancy (esophagus-2) is increasingly common, but its prognosis is poorly understood. This study aims to examine the overall, non-cancer related and cancer-specific survival of patients diagnosed with esophagus-2 compared to the first primary esophagus cancer (esophagus-1). We included primary esophagus cancer patients diagnosed from 1975 to 2019 in the Surveillance, Epidemiology, and End Results program. Esophagus-2 was identified in patients with a previous diagnosis of non-esophageal primary malignancy. Hazard ratios of overall, esophagus cancer-specific and non-cancer related mortality were estimated among patients with esophagus-2 compared to esophagus-1, adjusting for age, gender, tumor stage and other demographic and clinical characteristics. A total of 74,521 and 14,820 patients were identified as esophagus-1 and esophagus-2 respectively. Esophagus-2 patients suffered lower risk of esophagus cancer-specific mortality in initial 5 years but with similar risk thereafter, independent of tumor characteristics and treatment. In the first 5 years after diagnosis, patients with esophagus-2 had similar risk of overall mortality with those with esophagus-1 but increased risk thereafter. As for non-cancer related mortality, esophagus-2 patients had higher risk all along. Esophagus-2 patients should not be entirely excluded from clinical trial and a 3-year exclusion window is suggested. A conservative approach to manage esophagus-2 solely based on malignancy history is not supported but effort should be put into surveillance, prevention and management of the comorbidities and complications for the first malignancy.

Recommendations for Broadening Eligibility Criteria in Inflammatory Bowel Disease Clinical Trials.

Clinical trial recruitment for patients with inflammatory bowel disease (IBD) has become more challenging over time. We aimed to develop recommendations for broadening IBD clinical trial eligibility to improve the inclusion of a more representative patient population in a more efficient timeline. We applied the RAND/UCLA Appropriateness Method focused on broadening IBD clinical trial eligibility. A literature review was performed for 7 domains, each representing a different area related to trial recruitment. Based on these domains, 32 statements were developed. A questionnaire was sent to IBD specialists to anonymously vote on each statement with regards to its appropriateness and feasibility. After the first round of voting, participants met for a moderated discussion to review all statements. At the end of the discussion a second round of anonymous voting led to the final recommendations. The final round of voting resulted in 26 statements. All were rated as feasible and 25 of 26 rated as appropriate. Recommendations generally are to be more inclusive of complicated disease phenotypes, more liberal around safety criteria, to recognize the importance of non-invasive imaging and biomarkers, to minimize the washout period and to not enforce a minimum or maximum number of prior medications, to allow a recently recorded colonoscopy to count as a baseline study, and to be less restrictive of age. Recommendations to broaden clinical trial eligibility were found to be both appropriate and feasible with a high degree of agreement amongst an international group of IBD specialists.

Patients with a history of more than one cancer diagnosis: An opportunity to expand eligibility criteria?

e23019 Background: Patients with a history of more than one cancer diagnosis are increasingly common due to improved cure rates in early-stage cancers, and a demographic shift towards an increasing proportion of elderly patients with cancer due to longer life expectancy. Having a prior cancer diagnosis is a common exclusion criteria in clinical trials but represents a large untapped pool of patients that could increase enrollment in trials. We assessed if there are differences in the clinical characteristics, NGS testing rates and the rate of actionable genomic alterations in patients with NSCLC with a history of at least one other cancer diagnosis. Methods: We analyzed patients with a NSCLC diagnosis and an appointment scheduled between Oct 23, 2023 and Jan 14, 2024 at three US community oncology sites. All patients were enrolled in the Kaleido Registry and descriptive statistical analyses were performed on curated data. Results: 221 patients were identified (110 male/111 female). Median age was 72 (range 37-95). 157 (72%) patients had NSCLC as their only cancer diagnosis and 67 (28%) had a history of other malignancy with a median time interval since the last cancer diagnosis of 78 months (interquartile range 28-141 months ). 49 patients had a history of 1 other cancer diagnosis and 18 patients had a history of 2 or more. The most common diagnoses were breast (n = 16, 7%), colon (n = 7, 3.2%), prostate (n = 7, 3.2%) and bladder (n = 4, 1.8%) cancers. There were no differences in median age (73 yrs, range 57-91 vs (72 yrs, range 37-95), or sex distribution (30/34 vs 80/77) between patients with multiple diagnoses vs those with only NSCLC. There was not enough power to detect a difference in the rates of NGS testing rates or actionable genomic alterations (EGFR/ALK/ROS1/KRAS/RET/MET/NTRK/BRAF/HER2) in the cohorts (51% vs 64%, respectively). Conclusions: One in four NSCLC patients had a history of other cancer diagnosis. There were no significant differences in baseline characteristics or actionable genomic alterations. The median interval since the last cancer diagnosis was more than 6 years and less than a third had less than 3 years. These findings indicate that a significant number of patients with prior cancer diagnoses may be suitable candidates for clinical trials as their risk of recurrence of prior disease is likely low given long follow-up in this cohort.

Abstract PO3-17-07: Real-world experience with trastuzumab deruxtecan in patients with breast cancer: 6 month-interim analysis of an all-patient postmarketing surveillance in Japan

Abstract Background: Trastuzumab deruxtecan (T-DXd) is an anti-human epidermal growth factor receptor 2 (HER2) antibody-drug conjugate. T-DXd has shown great efficacy in HER2-positive breast cancer, hence receiving approval in Japan in March 2020. In Japan, all-patient postmarketing surveillance (PMS) is underway to evaluate the risk of interstitial lung disease/pneumonitis (ILD/p) in patients with breast cancer treated with T-DXd. Due to the limited generalizability of results from clinical trials, there is a need for more information about ILD/p in a real-world setting. Herein we present an interim analysis of the large-scale all-patient PMS. Methods: This is an observational, multicenter, all-patient PMS (jRCT1080225197) with an observation period of 18 months that enrolled all patients treated with T-DXd for recurrent/advanced HER2-positive breast cancer. Patients who initiated T-DXd treatment between May 2020 (launch date of T-DXd) and May 2021 were included in the interim analysis to ensure the observation period of 6 months from the initial treatment of T-DXd. This interim analysis is based on safety data from the first 6 months of 1204 patients. Data collected includes baseline characteristics and information on ILD/p. All potential ILD/p (identified based on the AE terms) reported by physicians were adjudicated by an independent ILD adjudication committee. The incidence of ILD/p was calculated from adjudicated drug-related ILD/p. Results: The interim analysis set included 1204 patients with median age of 60 years. Three of the 1204 patients (0.2%) received T-DXd as a first-line treatment, 30 (2.5%) as second-line, 1159 (96.3%) as third- line or later treatment. At baseline, 105 (8.7%) of patients had an Eastern Cooperative Oncology Group performance status (ECOG PS) 2 or greater, 8 (0.7%) had severe renal impairment (15≤ creatinine clearance (CLcr) < 30 mL/min), 4 (0.3%) had end-stage renal disease (CLcr < 15 mL/min), 5 (0.4%) had severe liver impairment (total bilirubin >4.5 mg/dL), and 32 (2.7%) had comorbid ILD/radiation pneumonitis. Those were defined as exclusion criteria in clinical trials of T-DXd. The median dose at the start of administration of T-DXd was 5.4 mg/kg (range:2.7-5.4). During the first 6 months from the initial treatment, T-DXd was discontinued in 403 (33.5%) of the 1204 patients. The most common reasons for discontinuation were disease progression in 232 (57.6%) of the discontinued 403 patients followed by ILD/p in 97 (24.1%) of the 403 patients. In the first 6 months, the incidence of all grade, grade ≥3, and grade 5 ILD/p were 8.2% (n=99), 1.7% (n=20) and 0.4% (n=5), respectively. The incidence of ILD/p stratified by baseline characteristics identified as potential risk factors of drug-related ILD/p is shown in Table. Conclusion: This is the first report demonstrating real-world experience with T-DXd in Japan. The interim analysis revealed useful information including patient and treatment profiles of T-DXd and the incidence of ILD/p during the first 6 months from the initial treatment in a real-world setting in Japan. The final analysis of the ongoing PMS is warranted for further evaluation. Incidence of interstitial lung disease/pneumonitis by patient baseline characteristics XX XX ILD/p: interstitial lung disease/pneumonitis, 95% CI: 95% confidence interval, CLCr: creatinine clearance using the Cockcroft-Gault equation * includes ILD/p, pulmonary fibrosis, radiation pneumonitis, chronic obstructive pulmonary disease, emphysema, and Asthma (Source: Powell CA, Modi S, Iwata H, et al. Pooled analysis of drug-related interstitial lung disease and/or pneumonitis in nine trastuzumab deruxtecan monotherapy studies. ESMO Open 2022;7(4):100554) Citation Format: Junji Tsurutani, Hideki Mizutani, Ayumi Tanabe. Real-world experience with trastuzumab deruxtecan in patients with breast cancer: 6 month-interim analysis of an all-patient postmarketing surveillance in Japan [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 PO3-17-07.

Abstract PS11-01: Brain metastases in metastatic breast cancer: prevalence per line of treatment and cumulative incidence in a cohort of 18075 real-world patients

Abstract BACKGROUND Historic data suggest that incidence of brain metastasis (BM) is relatively distributed over time in HER2-positive (HER2+) breast cancer (BC), occurs early in triple negative BC (TNBC), and occurs late in hormone receptor-positive (HR+) metastatic BC (mBC). However, the timing of BM relative to line of therapy has not been well described. We describe the prevalence per line of therapy and cumulative incidence of BM in a large real-world cohort of patients (pts) with mBC, by BC subtype and line of therapy. METHODS This analysis used data from the longitudinal US Flatiron Health de-identified database, which provides unstructured and structured electronic health record-derived data from >2.6 million pts with cancer in ~800 unique sites of care. Eligible pts had initiated a first line of treatment (index data) for mBC up to March 1, 2021, to allow for ≥2 years potential follow-up time. Baseline characteristics were assessed, and pts categorized by HER2 and HR status: 1) HR+, HER2+; 2) HR+, HER2–, 3) HR–, HER2+ and 4) TNBC (i.e., negative for HR and HER2). For the last two categories, HER2-low subsets were defined based on immunohistochemistry results (1+, 2+, or equivocal). Lines of therapy were derived using both treatment regimens and progression data. The primary outcome was the first diagnosis of BM. The prevalence of BM was evaluated by subtype, at the index date, and by the line of therapy. The cumulative incidence function (CIF) of BM was used to estimate the risk of BM in pts free of BM at the index date, and death was treated as a competing event. RESULTS Overall, 18075 pts were included (HR+, HER2+: 3062 pts [16.9%]; HR–, HER2+: 902 pts [5.0%]; HR+, HER2–: 12331 pts [68.2%] [HR+, HER2-low: 7062 (39.1%)]; TNBC: 1780 pts [9.8%] [HR–, HER2-low: 725 pts (4.0%)]). Median age at the index date was 64 years (interquartile range: 54, 73) and 10271pts (56.8%) had visceral metastasis. In total, 5951 pts (32.9%) had de novo disease, 12090 (66.9%) had recurrent disease, and 34 (0.2%) did not have available data for mBC type. The table shows the number of pts by line of therapy, prevalence of BM, and cumulative incidence of BM from the index date. Of the included pts, 1306 (7.2%) had a BM at the index date; the CIF was run on the remaining 16973 pts. Overall, 2248 pts (13.2%) had an incident BM event during follow-up (HR+, HER2+: 578 events; HR–, HER2+: 237 events; HR+, HER2–: 1119 events [HR+, HER2-low: 619 events]; TNBC: 314 events [HR–, HER2-low: 124 events]), 9314 had a competing event, and 5411 were censored. By fourth-line therapy, the prevalence of BM was 26.1% in HR+, HER2+; 37.1% in HR–, HER2+; 24.7% in TNBC (HR–, HER2-low: 27.9%); but remained low at 7.2% in HR+, HER2– (HR+, HER2-low: 9.4%). The cumulative incidence of BM at 60 months was 23% in HR+, HER2+, 34% in HR–, HER2+, 10% in HR+, HER2–, and, 22% in TNBC. Overall, the HER2-low subsets had BM prevalence and cumulative incidence that were very close to those that were HER2–. CONCLUSIONS This large analysis of real-world data demonstrates that the prevalence of BM across pts with mBC differs by tumor subtype and by line of therapy. Conversely, HER2-low status may have limited impact. The cumulative incidence of BM was highest in the HR–, HER2+ and TNBC subgroups, and lowest in the HR+, HER2– subgroup; despite this, due to the high proportion of HER2–, HR+ mBC cases, the HR+, HER2– group represented the largest number of BM events. These data emphasize the need for clinical and biologic predictors of BM and for strategies to prevent their onset, and provide information on the impact of BM inclusion and exclusion criteria in clinical trials for pts with mBC. Number of patients by line of therapy, prevalence of BM, and cumulative incidence of BM from the index date BM, brain metastasis; HR, hormone receptor, pts, patients; TNBC, triple negative breast cancer. Citation Format: Sarah Sammons, Jose Leone, Thibaut Sanglier, Peter Lambert, Filippo Montemurro, Raf Poppe, Eleonora Restuccia, Sara Tolaney, Nancy Lin. Brain metastases in metastatic breast cancer: prevalence per line of treatment and cumulative incidence in a cohort of 18075 real-world patients [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 PS11-01.

Abstract PO5-02-03: Does the recommendation of adjuvant CDK4/6 inhibitors implicate more ovarian suppression in premenopausal patients? A real-world study of a public and a private Argentinean institution

Abstract Introduction The recently published NATALEE trial has reported an increase of invasive disease free survival with the addition of ribociclib to hormone therapy during 3 years. Given the fact that aromatase inhibitors are required as the endocrine therapy backbone, premenopausal patients require ovarian function suppression (OFS) during CDKi treatment In the era of CDKi in the adjuvant setting, we hypothesize that the recommendation of GnRh analogs administration in addition to aromatase inhibitors will increase for premenopausal patients, given the inclusion criteria of this pivotal trial. For this reason, we explored in a retrospective cohort of a public and a private Argentinean institution to define whether the application of these criteria would imply an increase of the recommendation of OFS as part of the adjuvant endocrine treatment. Methods This was a multicentric retrospective cohort comprising premenopausal patients with early breast cancer diagnosis. Descriptive statistics were used to summarize data. The criteria for defining ribociclib recommendations were based on the phase III NATALEE clinical trial. Univariate analysis, including t and chi-square tests were used to determine differences between the populations that received and did not receive OFS, and between both participating institutions. p< 0,05 was considered to evaluate statistical significance. Results 191 premenopausal patients were incorporated in our analysis, and 48 (25.1%) received OFS. In this subgroup, mean age was lower (38.1 vs 44.2 years; p< 0.001) and the incidence of T3 (23.9 vs 6.5%; p=0.002), node-positive tumors (57.4 vs 28.9%; p=0.005), and prior chemotherapy treatment (75.5 vs 58.8%; p< 0.001) was higher. Among the 143 patients that did not receive OFS, 121 (84.6%) would have fulfilled clinical trial criteria for receiving ribociclib. No differences were observed according to the treating institution: 80.3 vs 87.8%; (p=0.22). The patient subgroup that would have met NATALEE criteria and did not receive OFS, had median age of 44.19 (SD 4.18), and had prior chemotherapy in 63.8% of the cases. Considering these characteristics, we observed that chemotherapy-induced amenorrhea and local institutional guidelines were the main explanations to understand why these moderate and high-risk patients did not receive OFS. Conclusion We observed that in premenopausal patients, the application of NATALEE criteria would result in an increase of the recommendation of GnRh analogues in around 80% of patients that had not received OFS in a retrospective cohort. This scenario may result in new challenges in treatment adherence and quality of life. In addition, this information is of special importance to carefully analyze the financial toxicity of a modern adjuvant approach that will be applied in a high proportion of eBC patients, especially in low and middle-income countries. Citation Format: Vanesa Lopez, Dana Narvaez, Jorge Nadal, Federico Waisberg, Adrian Nervo, Victoria Costanzo, Claudio Paletta, Fernando E. Petracci, Sergio Rivero, Alexis Ostinelli, Matías Chacón, Andrea Aguilar, Alejandro Kuzminin, Ageles Nico, Evelina Rovera, Naima Kassis, Maria Zapata Camaño, Carolina Almada, Maria Savignano, Gustavo Roganovich, Maria Eugenia Azar, Valeria Caceres. Does the recommendation of adjuvant CDK4/6 inhibitors implicate more ovarian suppression in premenopausal patients? A real-world study of a public and a private Argentinean institution [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 PO5-02-03.

European clinical practice guidelines for the definition, diagnosis, and treatment of oligometastatic esophagogastric cancer (OMEC-4)

IntroductionThe OligoMetastatic Esophagogastric Cancer (OMEC) project aims to provide clinical practice guidelines for the definition, diagnosis, and treatment of esophagogastric oligometastatic disease (OMD). MethodsGuidelines were developed according to AGREE II and GRADE principles. Guidelines were based on a systematic review (OMEC-1), clinical case discussions (OMEC-2), and a Delphi consensus study (OMEC-3) by 49 European expert centers for esophagogastric cancer. OMEC identified patients for whom the term OMD is considered or could be considered. Disease-free interval (DFI) was defined as the time between primary tumor treatment and detection of OMD. ResultsModerate to high quality of evidence was found (i.e. 1 randomized and 4 non-randomized phase II trials) resulting in moderate recommendations. OMD is considered in esophagogastric cancer patients with 1 organ with ≤ 3 metastases or 1 involved extra-regional lymph node station. In addition, OMD continues to be considered in patients with OMD without progression in number of metastases after systemic therapy. 18F-FDG PET/CT imaging is recommended for baseline staging and for restaging after systemic therapy when local treatment is considered. For patients with synchronous OMD or metachronous OMD and a DFI ≤ 2 years, recommended treatment consists of systemic therapy followed by restaging to assess suitability for local treatment. For patients with metachronous OMD and DFI > 2 years, upfront local treatment is additionally recommended. DiscussionThese multidisciplinary European clinical practice guidelines for the uniform definition, diagnosis and treatment of esophagogastric OMD can be used to standardize inclusion criteria in future clinical trials and to reduce variation in treatment.

HIV-related exclusion criteria in atopic dermatitis and prurigo nodularis clinical trials

HIV-related exclusion criteria in atopic dermatitis and prurigo nodularis clinical trials