tbuckley/cabot-search huggingface dataset:
A phase II single-arm trial of niraparib in platinum-sensitive metastatic castration-resistant prostate cancer with DNA repair defects (PLATPARP).
Authors: Erin Catherine Welch, Alexandra Torres, Joann Miller, Jennifer Louie, Daniel Lee, Naomi B. Haas, Samuel U Takvorian, Kara Noelle Maxwell, Susan M. Domchek, Vivek Narayan
Journal: Journal of Clinical Oncology (2024)

TPS255 Background: The optimal use of PARP inhibitor (PARPi) therapy is evolving for patients with metastatic castration-resistant prostate cancer (mCRPC) harboring germline and/or somatic homologous recombination repair gene mutations (HRRm). The sensitivity to platinum-based chemotherapy may predict improved clinical outcomes with PARPi. ‘Maintenance’ PARPi strategies are routinely used in patients with advanced ovarian and pancreatic malignancies with HRRm following an initial clinical response to platinum-based chemotherapy. Platinum-based chemotherapy is increasingly used in patients with mCRPC and HRRm as either a monotherapy or in combination with taxanes, but yields clinical responses of limited duration and is hindered by cumulative toxicities. We hypothesize that maintenance niraparib, a PARPi with demonstrated activity in mCRPC with HRRm, will prolong clinical responses to platinum-based chemotherapy with manageable toxicity in mCRPC patients harboring germline and/or somatic HRRm. Methods: We are conducting an open-label, single-arm, phase II study to evaluate the clinical benefit of maintenance niraparib in biomarker-defined, platinum-sensitive mCRPC patients. Eligible subjects harbor a pathogenic germline and/or somatic mutation in BRCA1/2, ATM, FANCA, CDK12, RAD51B, RAD54L, PALB2, CHEK2, HDAC2, or BRIP1 and have received at least 3 cycles (or minimum 9 weeks) of platinum-based chemotherapy for the treatment of mCRPC per investigator discretion. Following ≥4 weeks since completion of chemotherapy, subjects without evidence of clinical or radiographic disease progression receive investigational treatment with maintenance niraparib (200 mg daily). The primary objective is an improvement in 6 month PFS rate (PFS6) (H0: PFS6 rate 25%; H1: PFS6 rate 50%; power 0.77 with one-sided α = 0.05). Serial plasma samples are obtained for correlative analyses of markers of response and/or resistance to maintenance niraparib. Eleven of a planned total of 18 subjects have enrolled (N=4 germline BRCA2; N=1 germline BRCA1; N=3 somatic BRCA2; N=1 germline PALB2; N=1 germline ATM; N=1 germline CHEK2). This investigator-initiated study incorporates a novel, combined genetic and clinical patient-selection approach for PARPi therapy to optimize clinical outcomes. Clinical trial information: NCT04288687 .
Real-life data on [<sup>177</sup>Lu]Lu-PSMA-617: Descriptive analysis on the largest metastatic castration-resistant prostate cancer (mCRPC) cohort treated in France.
Authors: Guilhem Roubaud, François Somme, Philippe Barthelemy, Pierre Olivier, Vincent Massard, Anne Laure Giraudet, Aude Flechon, Sylvie Girault, Sophie Abadie Lacourtoisie, Clément Bailly, Caroline Viala, Yann Godbert
Journal: Journal of Clinical Oncology (2024)

129 Background: VISION study showed that [177Lu]Lu-PSMA-617 added to BSoC prolonged imaging-based progression-free survival and overall survival in patients (pts) with PSMA-positive mCRPC. French Health Authorities has granted a "cohort" early access for [177Lu]Lu-PSMA-617 in this indication. Methods: PSMA positive mCRPC pts pretreated with at least 1 taxane-based chemotherapy regimen and ≥1 androgen receptor pathway inhibitor (ARPI) were included. [177Lu]Lu-PSMA-617 (7.4 GBq) was administered up to 6 cycles every 6 weeks. Pts’ characteristics and safety data are described for the entire population. Efficacy was analyzed within a sub-population with 6 months follow-up min after 1st [177Lu]Lu-PSMA-617 injection. Adverse events (AE) grading was not evaluated. Results: From 12/1/2021 to 6/30/2023, 945 pts were included, and 535 pts were analyzed for efficacy. At data cut-off, 474 were still under treatment, and 471 stopped treatment due to disease progression (50.1%), AE (7.2%) or death (7.4%). 124 pts (26.3%) completed all 6 injections. Pts baseline characteristics: median age 73.2 (44-92) years; ECOG 0-1: 86.3%; median PSA level 70.9 (0.1 -6972) ng/ml; metastatic sites: bone 93.8%, lymph node 62.4%, liver 10.7%; previous taxane regimen: 97.1% of which 61.6% have received 2; prior ARPI treatment: 100% and 66.6% received 2 or more (median: 2). Concomitant treatment with ARPI was observed in 26.8%. In terms of efficacy results, the best imaging response was assessed by investigators (by RECIST 1.1 and PCWG3 on CT/bone scan and/or metabolic responses PET PSMA): 1.2% CR, 35.7% PR, 26.7% SD. 68.1% pts had a decrease in PSA level at any time point. Median time to PSA decrease was 1.22 (0.1–9.6) months. 12.8% (n= 121) of pts experienced &gt;1 treatment-related (TR) AE, including 99 pts with ≥1 serious AE. 3 fatal cases related to treatment have been reported. The most reported TRAEs were thrombocytopenia (5.4% of pts) and anemia (5.0% of pts). Conclusions: In this large real-life cohort of mCRPC treated with [177Lu]Lu-PSMA-617 pts are heavily pretreated, received less concomitant ARPI treatment and higher incidence of 2 prior taxane regimens compared to VISION study. Safety profile of [177Lu]Lu-PSMA-617 remains favorable. Since the cohort is still ongoing, updated results will be presented at ASCO GU congress, including longer follow-up period and higher number of pts who completed treatment.
Rural-urban disparities in prostate cancer survival: A population-based study.
Authors: Siqi Hu, Chun-Pin Chang, Mark W. Dodson, Vikrant Deshmukh, Michael Newman, Ankita Date, Alejandro Sanchez, Shane Lloyd, Brock ONeil, Mia Hashibe
Journal: Journal of Clinical Oncology (2024)

267 Background: Prostate cancer is the most prevalent malignancy among men in the United States. However, only a limited number of studies have explored the impact of rural-urban disparities in survival among prostate cancer patients with long-term follow-up. In order to investigate disparities in prostate cancer survival, we assess prostate cancer mortality and prognostic factors based on rural-urban residence. Methods: A cohort of 18,134 cancer patients with prostate adenocarcinomas diagnosed between 2004 and 2017 was identified. Residential location information at the time of cancer diagnosis was used to stratify on rural-urban residence. All-cause death and prostate cancer-cause death risks were estimated using Cox proportional hazard regression models. Results: Among prostate cancer patients, 15.1% resided in rural counties in Utah. Patients living in rural counties were different in demographic and clinical characteristics compared to their urban counterparts. An association was observed between rural residence and elevated risks of all-cause mortality (HR=1.19, 99%CI=1.10-1.29) and prostate cancer-specific mortality (HR=1.21, 99%CI=1.03-1.43). Elevated risks of both all-cause and prostate cancer-specific mortality were associated to factors such as unhealthy BMI, comorbidity index ≥1, family history of cancer or prostate cancer, single marital status, low income, low socioeconomic status, government insurance, earlier year of diagnosis, advanced prostate cancer stage, and extensive cancer treatment. Furthermore, the observed disparities in demographic and clinical profiles appeared to contribute to the disparities in all-cause and prostate cancer-specific mortality risks between rural and urban prostate cancer patients. Conclusions: Rural residence exhibited a significant association with the risk of prostate cancer-related and all-cause mortality. Patients residing in rural areas demonstrated distinct factors influencing mortality risks, encompassing both demographic and clinical aspects. These findings underscore the imperative for targeted interventions aimed at mitigating the rural-urban disparities in prostate cancer outcomes.
First-in-human safety, imaging and dosimetry of [<sup>68</sup>Ga]Ga-DPI-4452, a novel CA IX-targeting peptide, in patients with clear cell renal cell carcinoma.
Authors: Michael S Hofman, Ben Tran, Darren R. Feldman, Anna Pokorska-Bocci, Solen Pichereau, Jonathan Wessen, Mohammad B. Haskali, Richard Sparks, Olena Vlasyuk, Ivana Galetic
Journal: Journal of Clinical Oncology (2024)

373 Background: Carbonic anhydrase IX (CA IX) is overexpressed in clear cell renal cell carcinoma (ccRCC) and is associated with aggressive tumor behavior, treatment resistance and overall poor outcomes. DPI-4452 is a first-in-class, cyclic peptide that binds with high affinity to CA IX. Radiolabeling DPI-4452 with gallium-68 ([ 68 Ga]Ga-DPI-4452) or lutetium-177 ([ 177 Lu]Lu-DPI-4452) is an innovative, theranostic approach for identifying and treating patients with CA IX-expressing tumors. Compared with existing antibody approaches, a radiolabeled peptide may confer better characteristics for both PET-CT imaging and therapy. This first-in-human study (NCT05706129) is evaluating the theranostic potential of [ 68 Ga]Ga-DPI-4452 and [ 177 Lu]Lu-DPI-4452 in patients with unresectable metastatic ccRCC, colorectal cancer or pancreatic ductal adenocarcinoma tumors. Here we report safety, tolerability, pharmacokinetics, dosimetry and imaging characteristics of [ 68 Ga]Ga-DPI-4452 from the completed ccRCC imaging cohort. Methods: The DPI-4452 peptide contains a DOTA cage and is radiolabelled with [ 68 Ga]Ga. Following intravenous injection of [ 68 Ga]Ga-DPI-4452, patients underwent serial PET-CT imaging, urine and blood sampling to assess imaging characteristics, biodistribution, and dosimetry of [ 68 Ga]Ga-DPI-4452. Patients were followed for 7 days post-injection for safety observations. Results: A mean activity of 185 MBq [ 68 Ga]Ga-DPI-4452 was administered to 3 patients with ccRCC. No clinically significant toxicities were observed. PET-CT images showed rapid and sustained tumor uptake over 4 h, as well as rapid renal elimination. At 1 h, the maximum tumor standardized uptake value (SUV max ) across 36 lesions ranged from 6.8 to 211.6, with a mean of 64.6. Seventeen of these lesions (found in lymph nodes, lung, pancreas, parotid gland and other sites) were not detectable on prior contrast-enhanced CT. OLINDA dosimetry estimates revealed that the organs receiving the highest absorbed doses (mean [SD] mGy/MBq) were stomach wall (0.33 [0.10]), small intestine wall (0.33 [0.08]) and gallbladder wall (0.21 [0.12]), with a mean whole body effective dose of 0.06 [0.02] mSv/MBq. Absorbed doses in the kidney, liver and bone marrow were low. Over 80% of total administered radioactivity cleared from the bloodstream within 1 h. Conclusions: [ 68 Ga]Ga-DPI-4452 provides exceptional images in patients with ccRCC without clinically significant toxicity. Very high SUVs and tumor-to-background ratios suggest potential for use in both diagnostics and patient selection for therapy. The tumor retention and rapid elimination support potential of [ 177 Lu]Lu-DPI-4452 radioligand therapy. Clinical trial information: NCT05706129 .
Real-world treatment outcomes in patients with advanced renal cell carcinoma who receive axitinib plus pembrolizumab in the first-line setting in Canadian cancer centers.
Authors: Carissa Beaulieu, Sunita Ghosh, Camilla Tajzler, McKayla Kirkpatrick, Vincent Castonguay, Lori Wood, Jeffrey Graham, Denis Soulieres, Rahul K. Bansal, Daniel Yick Chin Heng, Antonio Finelli, Simon Tanguay, Aly-Khan A. Lalani, Bimal Bhindi, Georg A. Bjarnason, Rodney H. Breau, Naveen S. Basappa
Journal: Journal of Clinical Oncology (2024)

382 Background: The landscape of management of advanced renal cell carcinoma (aRCC) in the first line setting has changed dramatically over the past decade. Axitinib with Pembrolizumab (AP) is one of the combinations which demonstrated improved outcomes in the KEYNOTE 426 study. We report real-world outcomes and safety with this combination. Methods: The Canadian Kidney Cancer information system (CKCis) is a multi-institutional prospective RCC cohort. Patients ≥18 years with aRCC and clear cell histology who received AP as first-line therapy from January 1, 2017 to June 30, 2022 were included. Descriptive and actuarial statistics were reported for the following: progression free survival (PFS), overall survival (OS) and adverse events. Results: The cohort includes 222 patients.165 (74.3%) were male with a median age of 64.5 (37.0-87.7) years. Sixty-three (28.3%) patients were IMDC favourable-risk, 69 (31.0%) intermediate-risk, 45 (20.3%) poor-risk and 45 (20.2%) unknown. Median follow-up was 26.6 (range: 0.1 – 77.2) months. Of 222 patients, 119 discontinued treatment (53.6%) due to disease progression in 45.4% or toxicity in 29.4%. Median duration of treatment was 18.5 (range 0.1 to 72.4) months. PFS probability at 12 and 24 m was 63.8% and 49.9% respectively with a median PFS of 22.6 months (95% CI: 15.9-30.1). Survival probability at 12 and 24 m was 89.1% and 80.2% respectively with a median OS of 51.5 months (95% CI 38.0-NR). By IMDC criteria, intermediate risk median OS was 44.8 m (95% CI 41.5-61.6) and poor risk 33.6 m (18.5-NR). Most patients experienced toxicity requiring dose interruption/delay or discontinuation (n=180; 81.4%) The most common toxicities were diarrhea (73.3%), fatigue (54.4%), hepatotoxicity (50.0%), anorexia (26.1%), mucositis (22.2%), nausea (21.1%), palmar plantar erythrodysesthesia (15.6%), hypertension (13.3%), weight loss (13.3%) and proteinuria (11.7%). Others included pneumonitis (8.9%), thyroid dysfunction (6.7%) and colitis (4.4%). Conclusions: The real-world experience of patients with aRCC receiving AP in Canada is similar to the KEYNOTE-426 study in both outcomes and safety. These data continue to support its position as a standard of care in the first line setting for aRCC. Longer follow up and characterization of these patients is warranted.
Safety and efficacy of surgery in renal cell carcinoma with supradiaphragmatic tumor thrombus involving cardiac procedures.
Authors: Edouard Nicaise, Yash Shah, Benjamin Schmeusser, Benjamin Croll, Ellen Richter, McKenzie Hollon, Kenneth Ogan, Mani A. Daneshmand, Shishir K. Maithel, Viraj A. Master
Journal: Journal of Clinical Oncology (2024)

484 Background: Invasion of the IVC is a unique feature of RCC. Tumor extension into the supradiaphragmatic IVC carries high morbidity and mortality attributable to surgical complexity. It is unclear whether safety and efficacy have been shown to warrant cytoreductive surgery for metastatic RCC with concomitant thrombus. We present outcomes of cytoreductive and non-cytoreductive radical nephrectomy (RN) with supradiaphragmatic tumor thrombectomy (TT) involving cardiac surgery. Methods: We reviewed our nephrectomy database for patients with RCC and supradiaphragmatic tumor thrombus. RN with TT was performed by a single team from urology, surgical oncology and cardiothoracic surgery. Rank Sum for numerical and chi-square for categorical variables were used to test for differences between cytoreductive and non-cytoreductive RN. Kaplan Meier curves estimated cancer-specific survival (CSS) and overall survival (OS). Results: From 2006-2023, 43 patients underwent RN with supradiaphragmatic TT. The tableindicates notable clinical and surgical features. No patient participated in a related clinical trial perioperatively. No case required circulatory arrest. One patient required temporary dialysis and later passed from multi-organ failure. 5-year CSS was 12% vs. 78% (p=0.007) and OS was 11% vs. 53% (p=0.044) for cytoreductive and non-cytoreductive surgery respectively. Conclusions: RN with supradiaphragmatic TT is safe with durable treatment response in patients with non-mRCC. Although safety of cytoreductive RN is comparable, further investigation into the role of neoadjuvant therapy is recommended. [Table: see text]
The impact of perceived healthcare discrimination on health outcomes among patients with prostate cancer across racial and ethnic groups.
Authors: Daniel Sabater Minarim, Paul Riviere, Leah N. Deshler, Kylie M. Morgan, Elizabeth A. Duran, Matthew P. Banegas, Brent S. Rose
Journal: Journal of Clinical Oncology (2024)

268 Background: Black men face a disproportionately higher risk of mortality from PC (prostate cancer), and disparities in healthcare access have been associated with these outcomes. Discrimination in healthcare settings can profoundly affect health outcomes, especially for populations with significant health conditions. This study examined the association between race/ethnicity and perceived healthcare discrimination among individuals diagnosed with PC. We hypothesized that (1) racial/ethnic minorities with PC would be more likely to perceive healthcare discrimination and that (2) such perceived discrimination is associated with self-reported poor health. Methods: Using the 'All of Us' database, we focused on patients diagnosed with PC. We analyzed variables related to perceptions of respect, courtesy, and service quality from healthcare providers, categorized by race. These perception variables were then grouped to form a composite measure of "perceived healthcare discrimination." Multivariable logistic regression was used to study the effects of race/ethnicity on perceived discrimination and its subsequent impact on self-reported health, adjusting for demographics. Results: In our PC patient cohort of 3,129 participants, the race breakdown was: White: 2665, Black or African American: 150, Hispanic/Latino: 98, Other: 171, Asian: 27, Multirace: 18; Gender: Male: 3008, Gender Diverse: 121. A substantial number of patients with PC reported experiencing discrimination in healthcare settings. According to updated data, Black or African American patients were more likely to perceive discrimination with an Odds Ratio (OR) of 5.20, p &lt; 0.00. Hispanic/Latino patients had an OR of 1.53, p = 0.19, whereas Asians had an OR of 2.11, p = 0.17, and individuals of multiple races had an OR of 2.43, p = 0.16. In terms of health outcomes, patients who felt respected by their healthcare provider had an OR of 0.426 for reporting worse health, p &lt; 0.01. Conversely, those who perceived a lack of respect had an OR of 2.346 for poor health, p &lt; 0.01. Conclusions: Our findings enhance the understanding of the nuances of perceived healthcare discrimination among PC patients across racial and ethnic boundaries. Persistent racial differences underscore the need for systemic interventions in healthcare settings for PC patients. The identified negative experiences correlate with worsened health outcomes. Recognizing the instances of perceived healthcare discrimination in PC patients is paramount for elevating care quality and equity. Health systems are encouraged to take proactive measures in addressing these disparities, aiming for enhanced patient trust, improved communication, and superior outcomes.
Baseline CD8 lymph node avidity with 89-Zr-crefmirlimab in patients with metastatic renal cell carcinoma and response to IO therapy.
Authors: Peter D. Zang, Przemyslaw Twardowski, Delphine L Chen, Evan Thomas Hall, David Hays, Ian Wilson, Kristin Schmiedehausen, Michael Ferris, William Le, Michael A. Postow, Sumanta Kumar Pal
Journal: Journal of Clinical Oncology (2024)

375 Background: Prior studies with crefmirlimab, a 89-Zr labeled antibody with specificity for CD8+ cells, have shown a strong correlation with SUV uptake and IHC of the same lesions validating its use (Pal 2023). We predicted that responders to IO therapy would have higher CD8 lymph node avidity than non-responders. Methods: Pts enrolled had a diagnosis of mRCC and must have received IO therapy (CPI/TKI, CPI/CPI, or CPI monotherapy). Pts obtained a crefmirlimab PET/CT within 1 week before CPI infusion as baseline. PET intensity was determined using SUV Max , SUV Mean , SUV Peak . Highly avid lymph nodes (SUV Max &gt; 10) were quantified. Best overall response was determined using RECIST 1.1 criteria with SUV values and number of CD8 PET-avid lymph nodes compared using a Wilcoxon Signed Rank test in R. Results: A total of 17 pts (9 M: 8 F) were enrolled across 3 sites with 9 pts locally available for analysis. The median age of pts was 64 years old (54-71). Histology types included 12 clear cell (71%), 2 papillary (12%), and 3 indeterminate (17%). There were 3 responders (18%), 12 non-responders (71%), and 2 non-evaluable (12%). The most common treatment regimens patients received in descending order were cabozantinib + nivolumab (44.44%), nivolumab (33.33%), and ipilimumab + nivolumab (22.22%). Strong correlation was observed between CD8 cell density and SUV Mean (p &lt;0.0003 by Spearman’s correlation). The average number of CD8 PET-avid lymph nodes (defined as SUV Max &gt; 10) in responders was 6 versus 1.17 in non-responders (p = 0.025, 95% CI [1.99,7]). SUV Max , SUV Mean , SUV Peak across all CD8 PET-avid lymph nodes for responders were 15.58, 12.63, 11.44 and for non-responders were 9.86, 8.53, 7.79 respectively. The difference between SUV Max , SUV Mean , SUV Peak values reached statistical significance for all three values (p = 0.023 95% CI [3.42,7.84], p = 0.023 95% CI [2.64,5.84], p = 0.029 95% CI [1.18, 5.41] respectively). Conclusions: Our results show that pts with higher number of CD8 PET-avid lymph nodes at baseline was associated with better response to IO therapy; responders also had overall higher SUV uptake in CD8 PET-avid lymph nodes than non-responders. Our findings suggest that those with a more enriched CD8 phenotype trended towards better outcomes and may be a reliable predictor for IO therapy response. Clinical trial information: NCT03802123 .
Real-world effects of novel androgen receptor axis-targeted agents on oncological outcomes in non-metastatic castration-resistant prostate cancer: A multi-institutional retrospective study.
Authors: Naoki Fujita, Shingo Hatakeyama, Ryuji Tabata, Takahiro Yoneyama, Yasuhiro Hashimoto, Satoshi Sato, Chikara Ohyama
Journal: Journal of Clinical Oncology (2024)

142 Background: The benefits of novel androgen receptor axis-targeted agents (ARATs) on oncological outcomes in patients with non-metastatic castration-resistant prostate cancer (nmCRPC) in real-world settings are unclear. Methods: This multi-institutional retrospective study included 178 patients with nmCRPC treated between September 2003 and August 2022. Patients were divided into two groups: those who were treated with any novel ARATs, including apalutamide, enzalutamide, darolutamide, and abiraterone acetate, during any line of nmCRPC treatment (novel ARATs group) and those who were not (control group). Multivariable Cox proportional hazards regression analyses were performed to evaluate the effects of novel ARATs on metastasis-free survival (MFS) and overall survival (OS). Results: The median age and follow-up period after nmCRPC diagnosis were 76 years and 37 months, respectively. Of the 178 patients, 122 (69%) were treated with novel ARATs after nmCRPC diagnosis. The MFS and OS in the novel ARATs group were significantly longer than those in the control group ( P &lt; 0.001 and P = 0.020, respectively). In multivariable analyses, a prostate-specific antigen doubling time (PSADT) of &lt; 3 months and novel ARATs were independently and significantly associated with MFS and OS (Table). The effects of novel ARATs on MFS were consistently observed across subgroups stratified by age (&lt; 75 years or ≥ 75 years), history of radical treatment (no or yes), biopsy Gleason score (&lt; 9 or ≥ 9), clinical stage (≤ cT3 and cN0, or cT4 or cN1), and PSADT (≥ 3 months or &lt; 3 months). Conclusions: Novel ARATs were significantly associated with improved oncological outcomes in patients with nmCRPC in a real-world setting, regardless of tumor aggressiveness. [Table: see text]