tbuckley/cabot-search huggingface dataset:
Trastuzumab biosimilars interchangeability: Preliminary real-world data in neoadjuvant breast cancer setting.
Authors: Joao Soares Nunes, Ana Paula Prestes, Marcela Bechara Carneiro, Ana Claudia Machado Marra, Isabela Rovel Marquezini
Journal: Journal of Clinical Oncology (2024)

e23305 Background: Interchangeability (IC) among biosimilar compounds is still an issue not completely addressed, due to concerns on adverse events, immunogenicity, and efficacy. Many regulatory agencies around the world have adopted IC aside of appropriate clinical trials evaluation. Brazil’s Public Health System (SUS) has centrally provided trastuzumab (T) for breast cancer (BC) and firstly adopted biosimilars in 2020, after their regulatory approval 2 years before. After T biossimilar adoption there was an improvement of access for its all clinical indications, however different compounds had been offered to patients (pts) along their treatment. The aim of this study is evaluating the impact of these exchanges of types of T on patient-based registry. Methods: We reviewed all pharma and clinical data between 2020 and 2022 from all pts, stage III, Her2-Positive, who received neoadjuvant treatment based on chemotherapy plus trastuzumab in a Comprehensive Cancer Center in Southern Brazil. The main objective is measuring the rates of changes among T biosimilar compounds, and its impact in pathological response (pCR), toxicity and treatment-failure rates. Chi-square, Fisher’s Exact, t-test, or Mann-Whitney testing, as appropriate, was used to compare events between groups. Results: Along the studied period, SUS had offered 3 T biosimilars: ABP 980 (Amgen), CT-P6 (Celltrion), SB3 (Samsung), plus reference trastuzumab (Roche). The standard regimen was ACq21 4cycles followed by Taxane (Docetaxel q21 or weekly Paclitaxel) plus T 4cycles. 146 pts were eligible to analysis. 83 pts received only one type of T compound (non-interchangeability group – NICG), 63 pts received at least 2 different T compounds along the treatment (Interchangeability Group – ICG). Both groups were comparable in terms of clinical features (age, ER/PR status, menopausal status, PS, tumor size, and staging of axillary lymph nodes). Rate of IC along the time was 11%, 53% and 33% in 2020, 2021 and 2022, respectively. pCR was 32,5% in NICG versus 33,3% in ICG (p:NS). In total, 3pts had their treatments interrupted due to toxicity (1pt cardiac, 2pts hematologic). Conclusions: Although IC among biosimilars compound had been globally accepted, it was not clinically fully tested. Brazilian Ministry of Health, as the only provider, has a policy based on lowest cost for trastuzumab compound, causing constant changes along pts treatments. Furthermore, it is expected that Brazil has the potential to evaluate the IC in thousands of pts prospectively next years. Hereby, we could demonstrate preliminary based on retrospective data that exchange among different biosimilar compounds did not interfere significantly on pCR, nor raised any new safety or clinical concerns.
Assessing the relevance and requirement of a prostate cancer passport: A patient-centric survey.
Authors: Razia Aslam, Syed Muhammad Bilal Shah, Danial Hadi, Aoife Mc Cann, Emma Barron
Journal: Journal of Clinical Oncology (2024)

e23037 Background: Prostate cancer, a prevalent malignancy among men worldwide, necessitates a multifaceted approach to its management, encompassing diagnosis, treatment, and post-treatment care. The absence of a consolidated and accessible cancer information for prostate cancer patients prompts an exploration into the necessity and potential benefits of a dedicated Prostate Cancer Passport. This survey-based study seeks to elucidate patient perspectives and assess the demand for it. Methods: We Surveyed prostate cancer patients attending St James Hospital Medical Oncology OPD and day ward. The survey methodology integrated a diverse cohort of individuals representing varying demographics, encompassing age groups and socio-economic backgrounds. Questions were structured to gauge patient awareness, preferences, and perceived benefits associated with the adoption of a Prostate Passport. The survey was structured to gauge patient awareness levels regarding existing health record systems, preferences for a specialized Prostate Cancer Passport, and anticipated benefits associated with its implementation Furthermore, the survey seeked to elucidate potential concerns, barriers to adoption, and the anticipated impact on patient-provider interactions. Results: The survey’s findings indicate a significant interest among participants in the implementation of a specialized platform like the Prostate Passport, with more than 65% expressing enthusiasm about its potential benefits in improving healthcare management. However, 20% of patients reported not receiving any prostate cancer information booklet from their healthcare providers. Additionally, 30% of participants expressed dissatisfaction with communication with their medical team, while over 40% lacked confidence in their understanding of prostate cancer. Nevertheless, concerns related to data security were raised by more than 25% of patients, and approximately 23% identified potential barriers to adoption, such as interoperability with existing healthcare systems and ease of access across different healthcare settings. However, concerns regarding data security were highlighted by over 25% of patients and about 23% of patients identified interoperability with existing healthcare systems, and ease of access across various healthcare settings as potential barriers to adoption. Conclusions: The survey outcomes offer valuable perspectives on the distinct requirements and preferences of individuals facing prostate cancer. This data is crucial for customizing the Prostate Cancer Passport's design and functionalities to effectively cater to those needs. Our initial iteration of the prostate cancer passport has been completed and will be distributed to our oncology patients in the upcoming week. We plan to conduct a feedback survey in six months to gather insights and further enhance the passport based on user experiences.
The prevalence of RCTs in PARP and immune-checkpoint blockade combination trials: An appraisal of clinical evidence generation in oncology.
Authors: T. Anders Olsen, Ana Rosa Saez-Ibanez, Samik Upadhaya, Elad Sharon
Journal: Journal of Clinical Oncology (2024)

e23006 Background: PARP-inhibitors were developed to promote lethal genomic instability in cancers with homologous recombination repair (HRR) defects, ultimately receiving approval for patients with BRCA gene mutations. At the tumor microenvironment, DNA instability is linked to higher expression of immune activating signals such as PDL1. PDL1 is one of the primary targets for immune-checkpoint inhibitors (ICIs), receiving approval for numerous cancer types. In-vitro studies support mechanisms of possible synergy for PARP and ICIs in combination. Despite both therapy classes being available to oncologists for nearly a decade, the clinical benefit for these agents together remains unclear. Our study aims to appraise the global clinical trial landscape for trials testing combination PARP and PD1/PDL1 regimens. Methods: Search terms for all known approved or unapproved PD1/PDL1 and PARP inhibitors associated with trials registered on the National Library of Medicine’s website, clinicaltrials.gov, were included in the cohort as long as one interventional arm administered both agents. Qualitative and quantitative trial data features were collected from the Cancer Research Institute (CRI) Immuno-Oncology Intelligence Database and complemented with manually sourced information from trial registries and publications. Contribution of Effect (COE) was defined as trials with two or more arms that compare our combination regimen of interest to PARP or an ICI alone. The presence of randomization, eligibility for randomized-controlled trial (RCT) status as well as COE was determined by three reviewers separately with disagreements settled by committee decision. Results: In total, we found 188 clinical trials that enrolled 39,268 patients. A minority of 17 trials were phase I not considered as RCTs, leaving 37,827 patients across 171 trials for enrollment in phase II trials and beyond. Of these 171 trials, 80 (47 %) were single-arm studies without active comparator. Forty-nine (29%) used randomized assortment, 40 (23%) met criteria for an RCT and 33 (19%) met criteria for RCT with COE. In total, these 33 trials enrolled 14,803 patients. Of the 33, 17 (10%) enrolled patients with cancers that are approved for PARP blockade by the FDA and 11 (6%) employed genetic testing for HRR defects. Sponsorship ranged from 16 trials by industry, 6 by cooperative oncology group, 6 by academic institutions and 5 by the National Cancer Institute. Conclusions: Our study results highlight that the global clinical trial apparatus directs significant resources and patients towards trials with lower standards of evidence generation. Across sponsor types, there was a considerable number of trials that met the rigor of an RCT with COE. These findings show both promise and areas of improvement within the trial landscape to generate evidence relevant to the use of PARP and ICIs in combination.
Leveraging real-world data from multiple institutions to assess the rate of bilateral mastectomy after cancer genetics evaluations with genetic counselors.
Authors: Ashley Daley, Callan Russell, Timothy Joseph Stuhlmiller, Zachary Kaufman, Jill Davies, Colleen Caleshu
Journal: Journal of Clinical Oncology (2024)

e22551 Background: Genetic counselors (GCs) assess patients’ risk of cancer and counsel them on cancer screening and preventative measures, based on national guidelines. Prior studies have found that adherence to guideline-based care is higher after genetic counseling. Thus care provided by GCs leads to a variety of imaging and surgical services that can both improve patient outcomes and generate revenue for health systems, which can in turn help financially support cancer genetics programs. Research that quantifies such downstream services and revenue is lacking. We aimed to address this gap by using real-world data from multiple institutions to quantify the rate of bilateral mastectomies occurring after cancer genetics evaluations performed by GCs. Methods: We studied consecutive patients from a nationwide telehealth practice who underwent genetic counseling and cancer risk assessment with a GC after having germline genetic testing. Structured data obtained from multiple care sites via health information networks and manual chart review of electronic medical records was utilized to determine whether patients had bilateral mastectomies after the GC appointment. Results: Of the 460 consecutive patients seen by a GC, 30 were advised to consider bilateral mastectomy, based on their genetic test results and national guidelines. Data was available from the health information networks for all (29/29 (100%)) of these patients who live in the United States, with a mean follow-up of 2.7 years (SD 0.23). These 29 patients had a mean age of 43.3 years (SD 15.3), were all female, and carried mutations in BRCA2 (18/29 (62%)), BRCA1 (6/29 (21%)), or PALB2 (5/30 (17%)). Clinical data was collected from 468 locations, a median of 23 unique locations per patient. At the time of the GC appointment, 7/29 (24%) had active breast cancer, 19/29 (66%) were unaffected, and 3/29 (10%) had a history of previously treated breast cancer. Two patients were diagnosed with breast cancer after the GC appointment. 15/29 (52%) patients underwent bilateral mastectomy after the GC appointment, including most patients with active breast cancer (7/9 (78%)), 8/17 (47%) unaffected patients, and none (0/3 (0%)) with a previously treated breast cancer. Among those without breast cancer, the mean time from the GC appointment to the bilateral risk-reducing mastectomy was 8.6 months (SD 4.4). Conclusions: Half of patients who had bilateral mastectomy indicated because of their genetic test results elected to have mastectomy done after discussion of this guideline-based care option with a GC. As evidenced in prior research, bilateral mastectomy markedly reduces risk of breast cancer. In addition to improved patient outcomes, the revenue a health system receives from these surgeries can also help to support cancer genetics services.
Double reading performance and the impact of adjudication on progression-free survival estimations: Findings from a lung clinical trial.
Authors: Hubert Beaumont, Antoine Iannessi
Journal: Journal of Clinical Oncology (2024)

e23010 Background: The FDA recommends Blinded Independent Central Review (BICR) with double read for clinical trials with imaging. However, inter-reader variability is a concern in these trials. While studies have investigated the variability of RECIST, the primary response criteria, little attention has been given to the optimal association of readers. The evaluation of therapeutic response in phase III trials relies on the Date of first Progressive Disease (DoPD), with the Discrepancy Rate (DR) as the preferred index for measuring inter-reader variability in DoPD evaluation. Another important index measures readers' bias, assessing their tendency to over or under-estimate diagnoses. In cases of discrepancies, a third reader is brought in for adjudication. However, the impact of adjudication on trials' Progression-Free Survival (PFS) is not well-documented. Our study examines the variability in a lung clinical trial using RECIST, analyzing double reading performance, reader association prediction, and the impact of adjudication on PFS estimations. Methods: We retrospectively analyzed five phase III lung clinical trials using the RECIST 1.1 criteria in BICR with double reads. The trials involved 7 readers organized into 11 teams, each reader having participated in multiple trials and performed over 50 reads, resulting in 1017 patients' reviews. Our analysis included: Calculation of DR and bias for each team, and testing the correlation between DR and bias. Computation of the signed bias for each individual reader. Evaluation of a probabilistic model to predict the DR for each team and the bias for each reader. Comparison of PFS between single and double reads after adjudication and endorsement of one of the readings. Results: A multiple comparisons test did not reveal any difference between teams’ DR (Marascuilo test; q &gt; 0.05). The average DR across all teams was 39.9% [95%CI; 37.8; 41.9]. However, we did find significant differences in bias when comparing 9/55 pairs of teams (Marascuilo test; q &lt; 0.05). The range of absolute bias values was 20% to 100%. We did not find a correlation between bias and DR (p = 0.64). Additionally, when comparing the average bias value per reader, no differences were observed (Marascuilo test; q &lt; 0.05). We failed to predict teams DR and readers' bias. The endorsement rate of readers ranged [18%; 82%]. After adjudication, we found that 27% of the PFS were lower than the minimum value obtained from the single readers, in one case 20.6% shorter. Conclusions: Significant readers' bias has a notable impact on double readings, independent of the DR values. The performance of one reader cannot be generalized based on others. Additionally, adjudication significantly affects the PFS of clinical trials. These findings emphasize the importance of considering readers' bias and the potential consequences of adjudication in clinical trial assessments.
A geospatial analysis of neighborhood hot spots and socioeconomic disparities associated with high lung cancer incidence for targeted intervention in south Florida.
Authors: Ming Lee, Antonia Pryor Leavitt, Erin N. Kobetz
Journal: Journal of Clinical Oncology (2024)

e22525 Background: This study aims to identify the locations as well as specific socioeconomic disparities associated with high lung cancer incidences in South Florida (SF). The information is used to develop strategies for increasing smoking cessation and lung cancer screening rates in underserved communities via community outreach and engagement (COE). Methods: Sylvester Comprehensive Cancer Center’s catchment area in SF was studied and consists of three urbanized counties (Miami-Dade, Broward, and Palm Beach) as well as one rural county (Monroe), with a total population of 6 million. Age-adjusted incidence of lung cancer was calculated (2010-2019 Florida cancer registry data) for every census tract in the study area. Geospatial hot spot analysis was then applied to identify statistically significant clusters of census tracts with high age-adjusted lung cancer incidences. Socioeconomic data (American Community Survey) and smoking rates (CDC Places data) associated with the hot spot census tracts were then analyzed for risk factor identification and potential barriers to screening. Results: Hot spots census tracts for lung cancer in SF are generally associated with lower socioeconomic status, including lower income, higher percent of people living in poverty, more households with no vehicles, lower education levels, and higher percent of active smokers. Such socioeconomic disparities are most pronounced in the two highly populated counties of Miami-Dade and Broward. Palm Beach County’s hot spots include retirement communities, while those in the rural county of Monroe have the highest smoking rates. Conclusions: Using this analysis, our COE team began targeting hot spot communities for intervention with a specific focus on those where smoking rates are high, and no lung cancer screening facilities exist. The results demonstrate the utilities of geospatial data analysis for identifying locations and population segments for which increased cancer prevention efforts are needed. Targeting neighborhoods with the identified disparities for increased intervention in smoking cessation and lung cancer screening can help a COE team reach at-risk populations with limited resources more effectively. [Table: see text]
Comparative analysis of actionable gene reporting in targeted panels versus comprehensive NGS testing for solid tumor samples.
Authors: Chaugiang Duong, Roisin Puentes, Nathan Montgomery, Derek Lyle, Fernando J. Lopez-Diaz
Journal: Journal of Clinical Oncology (2024)

11185 Background: The landscape of actionable genes significantly influences clinical decisions in cancer diagnosis, prognosis, and treatment planning. In a clinical context, the selection of NGS panels hinges on striking a balance among informative data, insurance coverage, and the preferences of patients and healthcare providers. Molecular pathology reference laboratories commonly employ large-scale next-generation sequencing (NGS) testing, curating smaller, disease-specific targeted panels. This study investigates the prevalence of unreported actionable genes in real-world clinical samples subjected to disease-specific panels. Methods: We analyzed SNV/InDel DNA variants in 795 clinical solid tumor samples using the Illumina TSO 500 platform for comprehensive NGS panel testing of 517 genes. Comprehensive NGS panel-tested samples were intersected with disease-specific targeted NGS panels for breast (54 genes), brain (62 genes), colorectal (36 genes), and lung (44 genes). An artificial filter was applied to align targeted panels with patient disease. Variants were classified based on pathogenicity, and benign variants were filtered out. Detected variants were assessed for actionable mutations as defined by the FDA recognized OncoKB actionable gene database criteria. Additionally, 1484 lung patient samples tested with a lung-specific targeted panel were de-identified and unmasked to the comprehensive NGS tumor profiling to investigate the prevalence of actionable alteration beyond those covered by the disease-specific panel. Results: The study revealed that 3.2% of breast, 0% of brain, 66.2% of colorectal, and 2.7% of lung samples had additional actionable mutations undisclosed by the targeted panels. The number of actionable genes beyond those included in the targeted panels were 14 for breast, 2 for brain, 25 for lung, and 41 for colorectal cancer. This underscores the importance of comprehensive testing to fully capture each patient tumor’s actionable mutation profile. Conclusions: Our findings detect masked actionable mutations in down-sampled targeted panels and highlight the need for comprehensive testing to accurately identify actionable mutations in various cancer types. Reporting actionable mutations can significantly influence clinical decision-making, emphasizing the importance of NGS test selection in routine molecular diagnostics as well as the impact of integrating comprehensive NGS testing.
Adherence to cancer screening for patients with Li-Fraumeni syndrome: A report on our experience at Fred Hutchinson Cancer Center.
Authors: Josefine Bribiesca Rodriguez, Kevin Tatunay, Mercy Y Laurino, Marianne E Dubard-Gault
Journal: Journal of Clinical Oncology (2024)

e22553 Background: Li-Fraumeni syndrome (LFS) is a high-risk cancer predisposition syndrome where patients are at risk of developing multiple primary cancers, synchronous, and metachronous cancers in their lifetimes. Patients with LFS often serve as their own advocates to request and receive appropriate cancer screening as few clinicians have experience in caring for them and few clinics are adequately staffed to provide complex cancer screening coordination. Methods: Fred Hutchinson Cancer Center (Fred Hutch) is a large academic cancer care center associated with the University of Washington. In July 2020, Fred Hutch's clinical cancer genetic service launched a high-risk surveillance clinic for patients with hereditary cancer syndromes requiring services from multiple specialties. Our clinic has since helped patients with LFS receive coordinated cancer screening. Here we report on adherence to the Toronto protocol by reviewing patient demographic, cancer history and family history, and genetic records. Furthermore, we report on the number of visits, types of screening, and cancer diagnoses patients with LFS received since enrolling in the high-risk clinic. Results: A total of 112 patients with LFS were seen in the high-risk surveillance clinic between July 2020 and December 2023. Of these patients’ paths reviewed so far, 73 patients established with the clinic and received blood work and/or MRI imaging scans, and 42 were seen in at least one follow up visit. 2 patients with LFS were diagnosed with one or more new cancer diagnosis since enrollment, both have completed treatment, and both are without evidence of disease as of February 2024. Conclusions: The high-risk surveillance clinic was promptly utilized by patients with LFS for coordination of their complex cancer screening needs and to guide their next steps when triaging symptoms and concerns. While the clinic addresses a gap in cancer screening coordination, patients with LFS need wrap around care close to where they live which is difficult to accomplish in the Pacific Northwest.