tbuckley/cabot-search huggingface dataset:
Association between thymectomy and incidence of renal cell carcinoma (RCC).
Authors: Regina Barragan-Carrillo, Hedyeh Ebrahimi, Neal Shiv Chawla, Nicholas Salgia, Daniela V. Castro, Alex Chehrazi-Raffle, Nazli Dizman, Joann Hsu, Luis A Meza, Zeynep Busra Zengin, Alexis Ann LeVee, Abhishek Tripathi, Tanya B. Dorff, Cristiane Decat Bergerot, Paulo Gustavo Bergerot, Karyn Eilber, Kai Dallas, Sumanta Kumar Pal
Journal: Journal of Clinical Oncology (2024)

371 Background: Recently, thymectomy in adults has been linked to a higher incidence of several malignancies (Kooshesh et al NEJM 2023). Accompanying translational studies suggest that depleted T-cell production (both CD4+ and C8+) and decreased clonality may selectively drive the pathogenesis of immunogenic cancers such as RCC. We sought to confirm this finding in a large population-based cohort. Methods: We interrogated the California Office of Statewide Health Planning and Development (OSHPD) database, which collects information from all inpatient admissions, emergency room visits, and inpatient/outpatient procedures in the state. Patients who underwent thymectomy and nephrectomy (specifically for RCC) were identified from Jan 1, 2012, to Dec 31, 2019, using CPT and ICD-9/10 codes. The frequency of nephrectomy following thymectomy was computed. The frequency of both surgical interventions in the general population was derived by comparing their respective incidence in the OSHPD database against age-matched California census data. Chi square test was used to determine differences among groups. Fisher’s exact test was used to determine if the incidence of nephrectomy following thymectomy was different from the incidence of nephrectomy overall. Results: During the study period, 1,969 pts (mean age 56) underwent thymectomy and 31,093 pts (mean age 57) underwent nephrectomy. Relative to patients who underwent thymectomy, a larger proportion of patients undergoing nephrectomy were male (57% vs 45%) and Hispanic (28% vs 18%) (p&lt;0.01)., while a smaller proportion was Asian (7% vs 18%) (p&lt;0.01). Expressed as a percentage of the underlying age-matched population (18,343,792 pts), 0.01% of pts received thymectomy, and 0.17% of pts underwent nephrectomy. A total of 11 pts underwent nephrectomy following thymectomy, suggesting an incidence of 0.56% in this cohort. This was significantly higher than the incidence of nephrectomy in the population at large (P=0.002). The median age of patients who had a nephrectomy for RCC with a prior thymectomy was considerably younger than the general population who underwent a nephrectomy (mean age 52 vs. 57 years). Conclusions: In a large population-based study, we observed a significantly higher rate of nephrectomy for RCC in patients who had received prior thymectomy. These results bolster previous studies done in smaller datasets. Further work is needed to define causality and clarify the mechanism of this association.
Efficacy of perioperative pembrolizumab treatment in patients with resectable metastases from kidney cancer: The PE-PE study.
Authors: Roberto Iacovelli, Emanuela Fantinel, Davide Bimbatti, Sebastiano Buti, Lucia Bonomi, Mimma Rizzo, Caterina Accettura, Consuelo Buttigliero, Francesco Massari, Matteo Santoni, Paolo Andrea Zucali, Elisa Zanardi, Alessandra Mosca, Francesca Primi, Francesco Spina, Giuseppe Procopio, Sergio Bracarda, Fabio Calabrò, Lorenzo Antonuzzo, Chiara Ciccarese
Journal: Journal of Clinical Oncology (2024)

TPS495 Background: Radical metastasectomy and other local treatment strategies (including definitive radiotherapy, RT) can be carried out instead of systemic therapies for selected metastatic renal cell carcinoma (mRCC) patients (pts) with the aim of healing the patient even in an advanced disease stage. Recent data suggests a potential benefit from perioperative immunotherapy with immune checkpoint inhibitors (ICIs), as shown by the significant efficacy of adjuvant pembrolizumab in the M1 NED subgroup of the KEYNOTE-564 trial. Moreover, important activity of a short course of pembrolizumab has been demonstrated also in oligometastatic mRCC pts in combination with stereotactic ablative RT in the RAPPORT study. To date, no randomized trial has evaluated the concomitant use of pembrolizumab with surgery or definitive RT in mRCC compared to local therapy alone, which is the aim of our study. Methods: PE-PE study (NCT05578664) is a randomized, open-label, multicenter, phase 2 study evaluating the efficacy of pembrolizumab in delaying tumor progression in pts with oligometastatic mRCC who are candidates for radical surgery and/or definitive RT of the metastases. Eligible pts should have undergone previous nephrectomy and have maximum three metastases considered eligible for radical metastasis directed therapy (MDT; either metastasectomy or RT) and new disease must have appeared within 5 years from prior nephrectomy or metastasectomy. Pts will be randomized 2:1 to receive pembrolizumab at flat dose of 400 mg every six weeks for a total of 9 cycles (one year of therapy) and MDT from day 21 to day 42 of the cycle 1 (ARM A); or MDT alone within 42 days from randomization (ARM B). The primary endpoint is to assess the relapse free survival (RFS) defined as the length of time from randomization to the appearance of radiological progression in pts who receive pembrolizumab compared to those who do not. Secondary endpoints include: distant RFS (defined as the time from randomization to the appearance of distant metastases other those treated with surgery or RT), overall survival, and safety. Exploratory biomarkers analysis will be performed. The trial is actively recruiting. Clinical trial information: NCT05578664 .
Darolutamide plus androgen-deprivation therapy (ADT) in patients with high-risk biochemical recurrence (BCR) of prostate cancer: A phase 3, randomized, double-blind, placebo-controlled study (ARASTEP).
Authors: Alex Chehrazi-Raffle, Alicia K. Morgans, Jürgen E. Gschwend, Neal D. Shore, Ashley Ross, Felix Y Feng, Thomas A. Hope, Lucia Trandafir, Iris Kuss, Marie-Aude Le Berre, Heikki Joensuu, Karim Fizazi
Journal: Journal of Clinical Oncology (2024)

TPS254 Background: Patients with prostate cancer treated with radiotherapy (RT) or radical prostatectomy (RP) as primary therapy may develop BCR, defined as a prostate-specific antigen (PSA) increase without evidence of metastases on conventional imaging. Prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT), a more effective and precise imaging method, may detect small lesions in patients with BCR. Patients with BCR at high risk of metastatic progression and who have lesions identified by PSMA PET/CT need effective treatment to delay this progression. Darolutamide (DARO) is a structurally distinct and highly potent androgen receptor inhibitor, which significantly improved metastasis-free survival (MFS) and overall survival (OS) in patients with nonmetastatic castration-resistant prostate cancer (nmCRPC). The ARASTEP study (NCT05794906) is designed to evaluate whether DARO plus ADT improves radiological progression-free survival (rPFS) by PSMA PET/CT vs placebo (PBO) plus ADT in patients with BCR following primary therapy and PSMA PET/CT-positive lesions. Methods: Eligible patients must have prostate cancer treated by primary RT or RP followed by adjuvant RT (ART) or salvage RT (SRT), or RP alone if ART/SRT was not appropriate, with high-risk BCR (defined as PSA doubling time [PSADT] &lt;12 months and PSA ≥0.2 ng/mL after primary RP [± ART/SRT] or PSA ≥2 ng/mL above nadir after primary RT only), ≥1 PSMA PET/CT-positive lesion of prostate cancer without visible lesions on conventional imaging, and serum testosterone &gt;150 ng/dL. Approximately 750 patients from 184 sites worldwide will be randomized to oral DARO 600 mg twice daily or PBO, both with ADT, for 24 months unless, during this period, there is disease progression, unacceptable toxicity, or any other withdrawal criteria are met. Patients will suspend treatment after 24 months if PSA values are undetectable (&lt;0.2 ng/mL). Patients whose PSA values are still detectable (≥0.2 ng/mL) will continue with the study treatment until PSMA PET/CT progression. Image-guided radiotherapy or surgery is allowed within 12 weeks from randomization. Randomization is stratified by PSADT &lt;6 vs ≥6–&lt;12 months, intent to treat baseline PSMA PET/CT lesions with image-guided radiotherapy/surgery (Yes vs No) and distant ± locoregional vs locoregional-only metastases. The primary endpoint is rPFS by PSMA PET/CT, assessed by blinded independent central review (BICR). Secondary endpoints include MFS by BICR, time to CRPC, OS, quality of life, and safety. As of September 2023, 1 patient has been enrolled. Clinical trial information: NCT05794906 .
Disparities in uptake of new FDA-approved therapies for metastatic clear cell renal cell carcinoma.
Authors: Mitch Hayes, Melanie Buhlmann, L. Robert Gore, Logan Zemp, Philippe E. Spiess, Brandon J. Manley, Heather S.L. Jim, Jad Chahoud
Journal: Journal of Clinical Oncology (2024)

370 Background: Multiple new therapies for metastatic clear cell renal cell carcinoma (mccRCC) have been approved in the past decade. Real-world (RW) data on access to novel therapies and the impact on health-related disparities are limited. This study assessed RW access to novel therapies along with racial and social disparities for mccRCC patients and their impact on clinical outcomes. Methods: The longitudinal Flatiron Health database was queried for adult patients with mccRCC who received systemic treatments from Jan 2011 to Dec 2022 with at least two documented clinical visits. Patients &lt; 45 years old were excluded. Data was collected on age, gender, race, ethnicity, ECOG status, practice type, stage, smoking status, socioeconomic status (SES) defined by the Yost index, insurance status, overall survival (OS), and the first 14 treatments received. Patients were categorized as receiving a novel therapy if they received a first line mccRCC regimen during prespecified time windows starting on their first-line FDA approval date until 6 months later or when the next novel drug was approved, whichever date came later. Chi square test was used to assess variables across race. Univariable Cox proportional hazard models were used for OS analysis. R version 4.3.0 was used for programming. Results: 7,113 patients were included. 68.8% of the cohort was white, 7.1% Black, 1.4% Asian, 12.7% other, and 10.1% missing. Advanced age and receiving care in a community practice setting were associated with worse OS (CI 1.45-1.81 and CI 0.70-0.81, respectively), while SES was not (CI 0.81-1.01 for highest vs lowest group). Black race was associated with a 24% increased hazard of mortality compared to white race (CI 1.11-1.39, p=0.0003), and this was more pronounced in patients &lt;65 years old (CI 1.17-1.63, p=0.0001). 31.4% of patients received at least one novel therapy during the study period, and there were no differences by race. Receipt of novel therapy was not statistically associated with improved OS (p=0.1660). Conclusions: This is the first study in the immunotherapy era to highlight the worse OS of Black patients with mccRCC. Access to care at an academic center was associated with improved OS. Access to novel therapies did not differ between racial groups in the US using RW data. [Table: see text]
The effect of dual eligibility on the quality of active surveillance in patients with newly diagnosed prostate cancer.
Authors: Kassem S Faraj, Rodney Dunn, Brent K. Hollenbeck, Vahakn B. Shahinian, Lindsey A. Herrel
Journal: Journal of Clinical Oncology (2024)

266 Background: Dual eligible beneficiaries are a particularly vulnerable group of patients who qualify for Medicare due to age and Medicaid due to low income. Fully dual eligible beneficiaries have access to additional support services that may facilitate coordination for their prostate cancer evaluation and treatment, while others (i.e., partial dual eligible beneficiaries) do not have access to these services. The extent to which these additional support services impact the quality of care in men on active surveillance for prostate cancer is unclear. Methods: We performed a cohort study of Medicare beneficiaries diagnosed with prostate cancer between 2015 and 2019. We identified men who were managed with active surveillance and evaluated the quality of care they received in the first year after diagnosis. Ideal surveillance was defined as having both 1-2 PSA tests and a confirmatory test (i.e., multiparametric MRI, genomics, or biopsy) at 1 year. Men who had testing below or above these thresholds were categorized as having “underuse” or “overuse” of active surveillance testing. Differences in active surveillance measures were compared between beneficiaries who were fully dual eligible, partially dual eligible, and those who were not dual eligible. Results: Of 138,785 men with newly diagnosed prostate cancer, 4,611 (3.3%) were fully dual eligible and 2,031 (1.5%) were partially dual eligible. In the year after diagnosis, 1488 (32%) fully dual eligible men, 638 (31%) partially dual eligible men, and 31,133 (31%) non-dual eligible men were managed with active surveillance. Of these men, the use of ideal surveillance was lower in dual eligible beneficiaries (full-11%, partial-9%, non-dual-15%, p&lt;0.001). This corresponded to more underuse (full-70%, partial-74%, non-dual-63%) in dual eligible men and more overuse in non-dual eligible men (full-19%, partial-16%, non-dual-22%). The most common reasons for underuse were 1) both a lack of PSA and confirmatory testing in 26% of all men and 2) adequate PSA testing but no confirmatory test in 23% of all men. Conclusions: Our findings reveal that only a small minority of men with localized prostate cancer who are on active surveillance undergo ideal follow-up testing after diagnosis. Dual eligible men experienced less frequent ideal surveillance, potentially reflecting disparities in the quality of care for these vulnerable men. Partially dual eligible men had the worst rates of ideal surveillance and the highest rates of underuse, which may reflect the lack of support services that fully dual eligible men receive. Policymakers and healthcare providers aiming to improve the quality of active surveillance in the Medicare population should ensure that vulnerable groups have the resources needed to comply with the recommended testing.
Nivolumab plus cabozantinib (N+C) vs sunitinib (S) for previously untreated advanced renal cell carcinoma (aRCC): Results from 55-month follow-up of the CheckMate 9ER trial.
Authors: Maria Teresa Bourlon, Bernard Escudier, Mauricio Burotto, Thomas Powles, Andrea B. Apolo, Amishi Yogesh Shah, Camillo Porta, Cristina Suárez, Carlos H. Barrios, Martin Richardet, Howard Gurney, Elizabeth R. Kessler, Yoshihiko Tomita, Jens Bedke, Fong Wang, Peter Wang, Julie Panzica, Viktor Fedorov, Robert J. Motzer, Toni K. Choueiri
Journal: Journal of Clinical Oncology (2024)

362 Background: N+C demonstrated superior progression-free survival (PFS), overall survival (OS), and objective response rate (ORR) vs S in patients (pts) with previously untreated aRCC in the primary analysis of the phase 3 CheckMate 9ER trial (18.1 mo median follow-up). N+C maintained efficacy benefits vs S with 44.0 mo median follow-up. Here, we report updated efficacy in intent-to-treat (ITT) pts and by International Metastatic RCC Database Consortium (IMDC) risk, and safety with extended follow-up. Methods: Pts with aRCC were randomized to N 240 mg every 2 weeks + C 40 mg QD vs S 50 mg QD (4 weeks of 6-week cycles) until disease progression or unacceptable toxicity, with up to 2 y of N. The primary endpoint was PFS per RECIST v1.1 by blinded independent central review (BICR). Secondary endpoints included OS, ORR per RECIST v1.1 by BICR, and safety. Results: Overall, 323 pts were randomized to N+C and 328 to S (ITT). With 55.6 mo median (48.1 mo min.) follow-up for OS, median PFS was 16.4 vs 8.4 mo (hazard ratio [HR] 0.58, 95% CI 0.49-0.70) and median OS was 46.5 vs 36.0 mo (HR 0.77, 95% CI 0.63-0.95) with N+C vs S. ORR (95% CI) was 55.7% (50.1-61.2) vs 27.7% (23.0-32.9); 13.6% vs 4.6% of pts achieved complete response (CR); 6.5% vs 13.7% had progressive disease (PD), respectively. Median (range) time to response (TTR) was 2.8 (1.0-22.2) vs 4.3 (1.7-30.4) mo for N+C vs S, and median (95% CI) duration of response (DOR) was 22.0 (18.0-25.2) vs 15.2 (10.9-19.3) mo. Efficacy by IMDC favorable (FAV) and intermediate/poor (I/P) risk groups is reported in the Table. Among all treated pts (320 pts each arm), any-grade (grade ≥ 3) treatment-related adverse events (TRAEs) occurred in 97.5% (67.5%) vs 93.1% (55.3%) with N+C vs S. Any-grade TRAEs led to discontinuation of N or C in 28.1% of pts (N only, 10.0%; C only, 10.3%; N+C simultaneously, 6.6%; N+C sequentially, 1.3%) and of S in 10.9% of pts. Additional analyses in subgroups of clinical interest will be presented. Conclusions: With 55.6 mo median follow-up, N+C continues to maintain meaningful long-term efficacy benefits over S. No new safety concerns were identified. These results continue to support N+C as a standard of care for previously untreated aRCC. Clinical trial information: NCT03141177 . [Table: see text]
Fluorescence in situ hybridization utility in the care management of renal cell carcinoma (prospective study, 30 cases).
Authors: Rafik Ben Tayeb, Mohamed Mziyene, Layla Tahiri, Laila Bouguenouch, Hinde El Fatemi
Journal: Journal of Clinical Oncology (2024)

378 Background: In Morocco, Kidney cancer is the 18th most common tumour and the 19th lethal cancer in 2020. The average age of diagnosis is 65 years and men are more affected. Molecular studies of renal cell carcinoma (RCC) allowed the detection of several genetic abnormalities in each histological subtype. These aberrations got different diagnostic value depending on their specificity, prognostic implication and for some a therapeutic utility since the development of targeted therapies. The aim of our study is to evaluate the utility of fluorescence in-situ hybridization (FISH) in the diagnostic and the prognostic categorization of patients with renal cell carcinoma. Methods: We included prospectively cases of RCC diagnosed after histological examination and immunohistochemistry analysis for some cases. The methodology consisted in highlighting by FISH molecular abnormalities for each histological subtypes using Zytolight probes. Probes were chosen depending on the histological diagnosis and their corresponding molecular abnormalities. Results: A total of 30 cases of RCC were included. Clear cell carcinoma (ccRCC) represented 56,6%(17 cases) followed by papillary RCC (pRCC) with 20% (6 cases), chromophobe RCC (chRCC) with 10% (3 cases), 2 cases (6,6%) with uncertain diagnosis clear cell carcinoma or papillary carcinoma and one case of renal oncocytoma (RO) (3,3%), tubulo-cystic RCC tcRCC (3,3%). The FISH method supported the morphological diagnosis in all cases except in one biopsy diagnosed histologically as a ccRCC and this method allowed the diagnosis correction to a pRCC by the detection of a polysomy of chromosome 17 described in this histological subtype. The FISH method can also be used in prognostic categorisation of patients by the detection of some genetic aberrations with a prognostic implication like the loss of CDKN2a located in the long arm of chromosome 9 which predict a worse diagnosis. Conclusions: FISH method got an good performance in the diagnostic approach of RCC especially in cases with non-conclusive histology and immunohistochemistry. It can also be used in the prognosis of this tumour in addition to other histo-prognostic factors. This method will lead to more precision in diagnosis and better care management personalisation in RCC.
ProstACT GLOBAL: A phase 3 study of best standard of care with and without <sup>177</sup>Lu-DOTA-rosopatamab (TLX591) for patients with PSMA expressing metastatic castration-resistant prostate cancer progressing despite prior treatment with a novel androgen axis drug.
Authors: Charlotte Hawkins, Nat Lenzo, Julie Gibson, Tracey Brown, Neel Patel, Stefanie Martina, Colin Hayward
Journal: Journal of Clinical Oncology (2024)

TPS256 Background: The treatment of advanced prostate cancer (PC) is challenging, with undesirable side effects that impact patient quality of life. Radioimmunotherapy (RIT) can localize therapy to specific tumor cells in multiple organs to reduce or eliminate damage to normal tissue. The cell surface glycoprotein prostate-specific membrane antigen (PSMA) is an ideal therapeutic target as it is highly expressed by malignant prostate cells. There is a strong rationale for further investigation of the 177 Lu-labeled, chelator-conjugated antibody, 177 Lu-DOTA-rosopatamab, as a potential RIT candidate for the treatment of PC. Methods: In this multinational, multicenter, prospective, randomized, open label phase 3 study (NCT04876651), 387 patients with PSMA-expressing metastatic castration-resistant PC (mCRPC) that have progressed despite prior treatment with a novel androgen axis drug will be enrolled in a 2:1 ratio to receive either the best standard of care (SoC) or 2 single intravenous (IV) injections of 76 milicuries (mCi) each (equivalent to a 45 mCi/m 2 dose in a standard 1.7m 2 individual) of 177 Lu-DOTA- rosopatamab, given 14 days apart, plus best SoC. Eligible patients must have received prior therapy with either enzalutamide or abiraterone plus prednisone, and 1 line of prior taxane therapy or have refused or are ineligible for taxanes. Patients must have adequate organ function including at least 150x10 9 /L platelets, hemoglobin 10 g/dL, and have PSMA-positive disease on 68 Ga-PSMA-11 PET/CT imaging as confirmed by a central reader. Key exclusion criteria include small cell histology, increased risk of hemorrhage or bleeding, known brain or hepatic metastases, or history of stroke, seizure, or treatment with radioisotopes within 6 months prior to randomization. The primary endpoint is radiographic progression-free survival. Secondary endpoints include 5-year overall survival, tumor objective response rate, time to symptomatic skeletal event, progression free survival, and number of participants with treatment-related adverse events. Clinical trial information: NCT04876651 .