tbuckley/cabot-search huggingface dataset:
Unveiling the cost-effectiveness of CDK4/6 inhibitors in treating patients with HR+/HER2- metastatic breast cancer: A closer look at nonmedication expenses.
Authors: Asal Pilehvari, Wen You, Gretchen Genevieve Kimmick, Gloribel Bonilla, Roger Anderson
Journal: Journal of Clinical Oncology (2024)

1532 Background: Cyclin-dependent kinase (CDK)4/6 inhibitors have significantly enhanced survival outcomes in postmenopausal patients diagnosed with HR+ MBC. Their integration with endocrine therapy (ET) has become the standard of care in MBC treatment lines. There are limited economic evaluations of these innovative, yet costly, therapies. This study assesses the cost-effectiveness of these drugs using EHR derived data and administrative claims to estimate cost. Methods: We used the nationwide EHR-derived Flatiron Health (FH) de-identified database to identify 3,879 patients receiving 1st line (1L) treatment for HR+ MBC (2,137 received CDK4/6i+ET and 1,742 received ET alone) between Feb 2015 and Nov 2021. SEER-Medicare claims data was used to supplement the missing cost info in the FH database to quantify monthly medication costs, drawing data from Medicare patients continuously enrolled in PARTs A, B, and D between 2015 to 2021 for at least 24 months and specific to therapeutic approaches for MBC and overall healthcare costs. The costs were adjusted by the patient characteristic: age, race, specific ET or CDK4/6i drug, and Medicare dual eligibility. The effectiveness was measured as progression-free duration in months. All costs were adjusted for inflation. The Incremental Cost Effectiveness Ratio (ICER) analysis was conducted to examine the cost-effectiveness of CDK4/6i as compared with ET alone. Results: Average estimated monthly medication costs were $12,524 and $322 for CDK4/6i+ET and ET alone, respectively. On average, CDK4/6i+ET increased the estimated medication costs by $235,564 over the time to first progression and was associated with a gain of 3.2 months of progression-free survival as compared to ET alone, resulting in an ICER of $73,098 per month without progression. At a willingness-to-pay of $65,000 per month without progression, both groups have 50% probability of being considered cost-effective. Notably, the average estimated monthly non-medication costs (total costs-medication costs) for the CDK4/6i+ET group were $2,278 compared to $4,265 for the ET alone group (p&lt;0.001). On average, CDK4/6i+ET decreased the estimated non-medication costs by $ 22,427. For non-medication costs, the ICER drops to $7,178 per month without progression making the CDK4/6i+ET the dominant cost-effective choice over ET alone. Conclusions: Cost-effectiveness of treating HR+ MBC patients is primarily driven by the cost of CDK4/6i drug prices. However, findings highlight significantly lower overall non-medication healthcare costs using CDK4/6i+ET compared to ET alone in 1L treatment. These cost savings, however, are offset by the high medication costs of CDK4/6i. Thus, lowering the market cost of CDK4/6i drugs or targeting those who can benefit the most could shift the balance in favor of a cost-effective benefit from Medicare perspective.
The positive impact of Medicaid expansion on melanoma stage at presentation.
Authors: Shwe Win, Arya Amini, Badri Modi, Edward Wenge Wang, Miguel Angel Villalona-Calero, Ravi Salgia, Ramya Muddasani, Aaron Chan, Yan Xing
Journal: Journal of Clinical Oncology (2024)

1533 Background: This study aims to evaluate the impact of the Affordable Care Act Medicaid expansion on melanoma stage at presentation. Methods: 12,667 non-elderly patients (age 40-64) who were newly diagnosed with melanoma and known Medicaid expansion status were identified from The National Cancer Database. We excluded patients with private insurance, Medicare, or other government or unknown insurance. The time period for the cohort spanned from 2010 to 2020 which includes pre-expansion (2010-2013) and post-expansion periods (2014-2020). Year-to-year trend analysis and difference-in-difference (DID) analysis was performed to analyze tumor staging between states with Medicaid expansion (MES) and without Medicaid expansion (non-MES) before and after the expansion. Results: Out of the 12,667 melanoma patients (56% male, 95% white), 41% of patients were uninsured and 59% had Medicaid during 2010 to 2020. The percentage of patients without insurance decreased significantly from 51% in 2010 to 16% in 2020. There were 21% of patients with stage III and 18% with stage IV melanoma. The trend of melanoma stage at presentation over the study period was shown (Table). Notably, the stage IV melanoma at presentation decreased from 21% to 17% from 2010 to 2020 in MES. In contrast, stage IV melanoma at presentation increased from 20% to 23% over the same period of time in non-MES. After adjusting for confounders, DID analysis revealed a statistically significant decrease in stage IV melanoma at presentation (DID -0.04, p &lt; 0.001) as well as a statistically significant decrease in 3 year mortality (DID -0.05, p &lt; 0.001) between MES and non-MES before and after Medicaid expansion. In addition, the use of immunotherapy in stage IV melanoma in MES was significantly higher than non-MES (47% vs 41%, p &lt; 0.001). Conclusions: The findings reveal the positive impact of Medicaid expansion on melanoma stage at presentation and suggest that improved access to healthcare services can facilitate diagnosing early-stage melanoma and decreasing mortality rate. Despite these findings, there are still 16% of patients who still do not have insurance in 2020 which indicates that continued effort is needed to improve the outcomes of these uninsured patients.[Table: see text]
Geriatric assessment-directed supportive care intervention (GAIN-S)-implementation via telehealth in a lower-resourced community.
Authors: Tanyanika Phillips, Can-Lan Sun, Leana Cabrera Chien, Heeyoung Kim, Ashley Celis, Ty Lee, Africa Robison, Boryana Eastman, Amartej Merla, Heather Player, Ji-Hyun Kim, Hannah Asghari, Claudia Cuevas, Sherry Hite, Kayla Wei, Vani Katheria, William Dale
Journal: Journal of Clinical Oncology (2024)

1510 Background: Based on randomized controlled trials,ASCO guidelines recommend use of geriatric assessment (GA)-directed interventions for older adults with cancer. The translation of these models to lower resourced settings has been limited. We assessed the feasibility of implementing GA-directed supportive care (GAIN-S) via telehealth in a lower resourced community setting. Methods: A quality improvement study was conducted in a high poverty, limited access, and low resourced community oncology practice (City of Hope - Antelope Valley [COH-AV]). Eligible participants were 65+ years with a new diagnosis of a malignant neoplasm under evaluation for cancer therapy. Before starting therapy, patients completed: baseline GA, SupportScreen, and the Fulmer SPICES assessment. A geriatric nurse practitioner (GNP) reviewed GA results and implemented multidisciplinary supportive care interventions (GAIN-S) via telehealth between April 2020 and January 2023. Key evaluation measures included: number of patients who completed GAIN-S; number of referrals to multidisciplinary supportive care services and completion rate; advance directives (ADs); and patient satisfaction with telehealth visits. Participants’ demographics, including distance traveled for care, type of cancer, stage, treatment, and telehealth satisfaction items, were summarized using descriptive statistics. To analyze and visualize the implementation process, run charts were utilized. Results: 251 patients (mean age 74, 62% Non-Hispanic White, 22% live 60+ miles from COH-AV, 56% stage II or less, 30% received chemotherapy) completed baseline assessments. 242 had initial visits with GNP, 197 via televideo and 45 via telephone. GNP reviewed vulnerabilities with 209 patients and generated 460 referrals for supportive care services, with 85% of services implemented. Highest numbers of referrals were to pharmacy (177), social work (142), occupational therapy (76), and physical therapy (48). GNP discussed GA-guided care plans with all patients and 43 patients completed AD after discussion with GNP. Over 92% of patients were satisfied with telehealth-based GAIN-S in terms of both ease of visit and access to care with their provider and with telehealth. Conclusions: Telehealth-based GAIN-S has proven to be feasible in providing accessible healthcare to older patients with cancer in a lower resourced community setting. This approach, well-received by most patients, highlights the potential of telehealth in delivering GAIN-S effectively in such settings.
Longitudinal tumor-wide sampling of glioblastoma reveals diverse genomic drivers of the earliest clonal expansion at diagnosis and recurrence.
Authors: Benjamin Joshua Lerman, Chibo Hong, Lee Chen, Ivan V Smirnov, Joanna J. Phillips, Anny Shai, Janine Lupo, Joseph Costello
Journal: Journal of Clinical Oncology (2024)

2009 Background: Despite decades of clinical trials, glioblastoma (GBM) remains a rapidly fatal disease. Much of therapy resistance in GBM is attributed to intratumoral heterogeneity in which subclones rapidly evolve and treatment-resistant cell populations emerge. Understanding heterogeneity at diagnosis and its relationship to the origins of recurrence are critical to selecting therapies that are efficacious across the entire tumor. However, few genomic studies go beyond analyzing single tumor samples per patient. Methods: A spatially oriented, whole tumor sampling approach was used to obtain 43 biopsies from 3 GBMs at diagnosis and recurrence. Pyclone and ClonEvol were applied to whole exome sequencing to reconstruct clonal evolution, FACETs identified copy number variations and HATCHet estimated tumor purity. Candidate driver mutations were evaluated in relation to the Catalogue of Somatic Mutations In Cancer. Results: A single founding clone and multiple subclones were identified for each diagnosis-recurrence pair. Tumor-wide clonal alterations representing initial clonal expansions of these GBMs included both canonical changes (Chr 7 gain, Chr 10 loss, CDKN2A deletion, EGFR amplification) and a diverse set of large-scale copy number variations (Chr 19, 20 gain), driver mutations (PTEN, KDR, CDH11, CNTNAP2), and fusions (LIMCH1::UCHL1, KANK::DOCK8). A second subset of alterations (Chr 8 gain, ATRX mutation), appeared to be tumor wide at diagnosis but were not identified at recurrence. Cancer drivers were also present subclonally, including CDKN2A deletion, MDM2 amplification, and mutations in NF1, and GRM3. Evolutionary trees consisted of 5 generations of clones in Patient 323 (P323), 3 in P454, and 4 in P534. Divergence of the recurrent tumors from their matched primary occurred in the second generation in P454 and P534 and in the third in P323. As a result, an average of 37% of potential drivers of oncogenesis and clonal expansion across the cohort appear after divergence. Furthermore, each recurrent tumor contained at least one tumor wide driver alteration that was subclonal or undetected at diagnosis. Conclusions: Whole-tumor sampling of three GBM patients at both diagnosis and recurrence identified a diversity of genomic drivers and deeper and more complex genetic roots of individual GBM than previously seen in single-biopsy studies. Tumor recurrences consistently arose from a single subclone that diverged early in evolution of the primary tumor and contained clonal drivers either not detected or subclonal in the primary—suggesting a role for these drivers in persistence and expansion. In the age of personalized medicine, our study highlights the clinical potential of tumor wide sampling in identifying therapeutic targets that could avoid heterogeneity-related therapeutic failures.
Deep learning vs traditional breast cancer risk assessment models: Are we offering supplemental services to those who benefit the most?
Authors: Leslie R. Lamb, Heba Albasha, Sarah Mercaldo, Andrew Carney, Constance D Lehman
Journal: Journal of Clinical Oncology (2024)

1556 Background: Mammography-based deep learning (DL) risk stratification models improve discriminatory accuracy in predicting future breast cancer compared to traditional risk models; however, decisions for and insurance payment of supplemental services such as MRI are driven by traditional scores. The purpose of this study was to compare risk scores and cancer detection rates in patients identified as increased risk by DL vs traditional models in a large screening mammography cohort. Methods: This multisite study included consecutive patients ≥40y undergoing routine bilateral screening mammography from 9/2017 to 1/2022 at five facilities. Tyrer-Cuzick version 8 (TC) and National Cancer Institute Breast Cancer Risk Assessment Tool (BCRAT) 5-year and lifetime models and a DL 5-year model were used to assess risk. The following thresholds were used to define intermediate risk: ≥1.67% for TC and BCRAT 5-year, 2.2 for DL model and high risk: ≥20% for TC and BCRAT lifetime, ≥6.0 for DL model. Patients were included if all risk scores were available. Patient demographics were retrieved from electronic medical records and cancer outcomes through regional tumor registry linkage. The proportion of increased-risk patients and cancer detection rates (CDR [cancers per 1000 women screened]) across models were compared using Pearson’s Chi-square test. Results: 148476 exams in 69464 patients (mean age 58.0y [IQR: 50.0-67.0]) were performed. 81.7% (119386/146075) of exams were in White patients and 18.3% (26689/146075) in races other than White. CDR of those classified as intermediate risk by DL was 7.1 (450/63109) vs 4.7 (320/68545; P&lt;0.001) by TC and 4.2 (300/70831; P&lt;0.001) by BCRAT, and as high risk was 20.6 (305/14772) by DL vs 3.9 (64/16442; P&lt;0.001) by TC and 5.0 (29/5782; P&lt;0.001) by BCRAT. 13.0% (19248/148476) were classified as intermediate risk by DL but not by TC or BCRAT, with a CDR of 6.0 in this cohort. 32.0% (47435/148476) were classified as intermediate risk by TC or BCRAT but not by DL with a CDR of 1.1. 8.5% (12577/148476) were classified as high risk by DL but not by TC or BCRAT with a CDR of 20.8. 11.1% (16451/148476) were classified as high risk by TC or BCRAT but not by DL with a CDR of 1.9. Conclusions: A significant proportion of patients identified as increased risk by DL model are not assessed as increased risk by commonly used risk models, effectively excluding them from accessing potentially life-saving supplemental services. DL scores met the American College of Radiology's acceptable CDR on screening mammography (≥2.5) regardless of traditional scores, however, elevated traditional scores in the absence of elevated DL scores did not meet acceptable standards. Risk assessment guidelines incorporating DL models are necessary to capture patients who benefit the most.
AI-enabled digital test to predict disease recurrence for patients with early-stage invasive breast cancer and performance in a MammaPrint low-risk cohort from the Netherlands with a median 6-year follow-up.
Authors: Michael J. Donovan, Claudia Meurs, Gerardo Fernandez, Abishek Sainath Madduri, Aaron Feliz, Jack Zeineh, Rebecca DeAngel, Pieter Westenend
Journal: Journal of Clinical Oncology (2024)

1569 Background: Traditional invasive breast cancer (IBC) grading, although useful, remains limited due to diagnostic subjectivity and absence of phenotypic diversity including the recently observed importance of tumor epithelial – stromal interactions and lymphocyte content-distribution. We developed and validated a clinical grade digital test (PreciseDx Breast, PDxBr) which combines image-derived Artificial Intelligent (AI)-grading features and clinical data (i.e. age, stage, tumor size, LN status) to predict recurrence in early-stage IBC and sought to understand performance in a MammaPrint cohort with outcome data. Methods: A MammaPrint cohort with median 6-year follow-up was identified at the Laboratory of Pathology, Dordrecht, the Netherlands (NTH). H&amp;E stained images (digitized at Philips, Eindhoven, NTH) with clinical data (from the pathology and Dutch cancer registries) including demographics, pathology results, MammaPrint risk classification, treatment type and recurrence events were obtained. Performance of the PDxBr validated model (AI-grade + clinical) on the MammaPrint cohort was evaluated using the AUC/concordance index, along with NPV, PPV, Hazards ratio (HR), sensitivity, and specificity. Results: 250 patients, median age 57 years, majority stage 1-IIIa, 100% HR+ve, Her2-ve, 84% LN-ve, 67% grade 2 and 66% MammaPrint low risk. There were 15 events (6%: 7 deaths, 3 second primaries,4 metastases and 1 local regional). PDxBR model classified 134 patients as high risk and 116 as low with 10 of 15 (67%) events identified as high risk. The NPV for PDxBr was 96% with a HR 1.63, Se 70%, Sp 46% vs. MammaPrint with an NPV of 94%, HR of 0.96, Se 40%, Sp 66%; identifying only 5 of the 15 events (33%) as high risk while missing 10. Of note, the AI- grade/imaging model (without clinical features) yielded an NPV of 95% with a HR of 1.46, Se 70%, Sp 42% and correctly identified 10 of 15 events. Conclusions: The results from this observational study suggest that triaging patients with the PDxBr test could potentially be adjunctive to the management decision process of patients with early-stage IBC including the use and subsequent interpretation of genomic tests such as MammaPrint. Additional studies are underway to confirm these initial findings.
Relationship between immune-inflammatory markers and clinical features and deepness of tumor response and prognosis of patients with PD-L1 ≥50% metastatic NSCLC receiving first-line immunotherapy.
Authors: Xixi Zheng, Lili Zhou, Juan An, Xiaosheng Ding, Yichun Hua, Hui Shi, Weiran Xu, Xiaoyan Li
Journal: Journal of Clinical Oncology (2024)

e14547 Background: Patients with programmed cell death-ligand 1 (PD-L1) ≥50% metastatic non-small cell lung cancer (NSCLC) treated with first-line immunotherapy have heterogeneous clinical assessment and outcomes. In this study, we sought to identify features of patients with metastatic NSCLC who achieved high deepness of response (HDPR) to first-line immunotherapy, and how these might differ from features predictive of non-high deepness of response (NHDPR). The influence of clinical features on prognosis of patients with PD-L1 ≥50% were further clarified. Methods: This retrospective study analyzed patients with PD-L1≥50% metastatic NSCLC treated with first-line immunotherapy at Beijing Tiantan Hospital between July 2020 and December 2023. All the patients had at least one measurable lesion in lung according to the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. HDPR was defined as deepness of lung tumor response ≥50%, while NHDPR was defined as deepness of lung tumor response &lt;50% or tumor enlargement. Tumor PD-L1 expression, target mutation, neutrophil-to-lymphocyte ratio (NLR), lactic dehydrogenase (LDH) level, and other prognostic variables were analyzed to identify characteristics enriched in patients achieving HDPR compared to NHDPR. We also investigated the effects of these variables on first-line progression-free survival (PFS) and overall survival (OS) of the patients. Results: A total of 17 patients were included in our retrospective analysis. Seven (41.2%) patients achieved HDPR (range: -50%, -72%) and ten (58.8%) patients achieved NHDPR (range: -13%, -45%). Seven (41.2%) patients had central nervous system (CNS) metastases at the first diagnosis of lung malignancy, and their CNS target lesions shrinkages were observed after therapy (range: -32%, -100%). Lower Th/Ts ratio ( P=0.01) and drug resistance mutations (TP53/KRAS/EGFR) ( P=0.001) were found enriched for NHDPR compared to HDPR. However, no differences were found in tumor PD-L1 expression, NLR, LDH, B lymphocyte subset, NK cell subset, pathological type, T-stage, smoking index, ECOG score, immunotherapeutic schemes, or CNS metastases between the two groups ( P&gt;0.05). With a median follow-up of 26.0 months (range: 17.2-34.8 months), the median first-line PFS and OS were 9.0 months (95% CI: 5.0-13.0) and not reached (NR), respectively. The NLR was identified as an independent prognostic factor on first-line PFS. Patients with an NLR≥4 exhibited a worse median PFS (7.0 months vs. NR; P=0.033; 95%CI: 1.2-80.2) than those with an NLR&lt;4 following first-line immunotherapy. Conclusions: Among patients with PD-L1≥50% metastatic NSCLC who received first-line immunotherapy, lower Th/Ts ratio and drug resistance mutations showed a diminished tumor response and higher NLR ratio exhibited a worse median PFS.
A phase 0/1 trigger trial of BDTX-1535 in patients with recurrent high-grade glioma (HGG) with EGFR alterations or fusions.
Authors: Nader Sanai, Yoshie Umemura, Vahuni Karapetyan, Tigran Margaryan, Dylan Huttenlocher, Jocelyn Harmon, Amy Hong, Wonsuk Yoo, An-Chi Tien, Artak Tovmasyan, Shwetal Mehta
Journal: Journal of Clinical Oncology (2024)

2069 Background: This Phase 0/1 clinical trial evaluates the pharmacokinetic (PK), pharmacodynamic (PD), and clinical response of recurrent high-grade glioma (HGG) patients with EGFR alterations and/or fusions to the ATP-competitive, irreversible EGFR inhibitor, BDTX-1535. Methods: Recurrent HGG patients with EGFR alterations (Arm A) or EGFR fusions (Arm B) received 5 days of BDTX-1535 (200 mg) prior to planned resection at 2-4 hours following the final dose. In the Phase 0 component of the study, total and unbound drug concentrations were measured in tumor tissue (Gadolinium enhancing and non-enhancing regions), cerebrospinal fluid (CSF), and plasma using validated LC-MS/MS methods. A PK ‘trigger’, defined as unbound drug concentration above 5-fold biochemical IC50 in Gadolinium (Gd)-nonenhancing tumor, determined eligibility for Phase 1. PD response was assessed by quantification of percentage of positive pEGFR, pERK and MIB-1 cells in the surgical tumor tissue compared to baseline pre-treatment tissue. Patients with tumors exceeding the PK threshold for unbound drug concentration were eligible for expansion phase therapeutic dosing of BDTX-1535. Results: A total of 7 patients with recurrent glioblastoma (Arm A) were enrolled in the Phase 0 component of the study. Two patients were excluded from PK analysis due to pseudoprogression. The mean unbound concentrations of BDTX-1535 in Gd-enhancing and nonenhancing tumor regions were 16.0 nM and 10.5 nM respectively. Four of five (80%) evaluable patients exceeded the PK threshold. The suppression of pEGFR and MIB1 was observed in 40% and 60% of patients, respectively. No serious adverse events were observed among patients in the Phase 1 component of the study and a clinical readout is planned in Q2 2024. Conclusions: BDTX-1535 is well-tolerated in recurrent HGG patients, achieves pharmacologically relevant concentrations in Gd-nonenhancing tumor tissue and is associated with suppression of EGFR signaling. Clinical trial information: NCT06072586 .