tbuckley/cabot-search huggingface dataset:
Mayo Adhesive Probability score to predict renal function following partial nephrectomy.
Authors: Edouard Nicaise, Benjamin Schmeusser, Yash Shah, Cameron Futral, Sriram Ambadi, Nahar Imtiaz, Dattatraya H. Patil, Kenneth Ogan, Viraj A. Master
Journal: Journal of Clinical Oncology (2024)

379 Background: Mayo Adhesive Probability (MAP) score, which measures adherent perinephric fat in renal cell carcinoma (RCC), is associated with surgical complexity and cancer progression in patients undergoing partial nephrectomy (PN). PN carries perioperative risk but preserves renal function versus radical nephrectomy (RN). We analyzed whether MAP score can predict long-term postoperative renal function in localized RCC patients who underwent PN. Methods: We reviewed our nephrectomy database to identify pT1-T3a RCC patients who underwent PN. Patients with metastatic disease, IVC thrombus, multiple masses, and prior nephrectomy were excluded. Estimated glomerular filtration rate (eGFR) was calculated using the CKD-EPI 2021 formula and patients with values &lt;15mL/min/1.73m2 were excluded. We calculated MAP scores from preoperative cross-sectional imaging and dichotomized patients into low (1-3) versus high (4-5) cohorts. Continuous and categorical outcomes were compared using ANOVA and chi-square tests. A hierarchical generalized linear mixed effect model was used to evaluate predictors of long-term, postoperative eGFR following PN. Results: 314 patients were identified and 97 (30.9%) were classified with a high MAP score. These patients were older (64.5 vs. 58.3 years, p&lt;0.001), more often male (85.6% vs. 52.5%, p&lt;0.001), and white (79.4% vs. 67.7%, p=0.016). MAP score was associated with obesity (59.8% vs. 42.9%, p=0.006), diabetes (36.1% vs. 22.6%, p=0.013), hypertension (82.5% vs. 63.1%, p&lt;0.001), and severe CCI (5+; 35.1% vs. 23.5%, p&lt;0.001). No difference was observed in the rate of current or former smokers. Final tumor size was greater among patients with high MAP (4.1 vs. 3.4cm, p&lt;0.001) but no difference was noted in pT stage. Rate of acute renal failure postoperatively (dialysis or eGFR &lt;15 within 30 days) was similar between the two cohorts (1% vs. 1.4%, p=0.797). The tablepresents the model used to evaluate postoperative eGFR predictors. Conclusions: High MAP score predicts a greater eGFR decline following PN for localized RCC. Considering the risks of PN, MAP scoring may indicate surgical complexity and inform shared decision-making when considering nephron-sparing surgery for RCC. [Table: see text]
ARTO trial: Overall survival analysis from a randomized phase II trial testing the benefit of adding stereotactic body radiotherapy to abiraterone acetate in patients with oligometastatic castrate-resistant prostate cancer.
Authors: Giulio Francolini, Vanessa Di Cataldo, Pietro Garlatti, Beatrice Detti, Saverio Caini, Alessio Bruni, Gianluca Ingrosso, Rolando Maria D'Angelillo, Anna Rita Alitto, Matteo Augugliaro, Luca Triggiani, Silvana Parisi, Gaetano Facchini, Marco Banini, Gabriele Simontacchi, Isacco Desideri, Icro Meattini, Richard K. Valicenti, Lorenzo Livi
Journal: Journal of Clinical Oncology (2024)

132 Background: ARTO (NCT03449719) is a multicentre, randomized phase II trial testing the benefit of stereotactic body radiation therapy (SBRT) addition to abiraterone acetate (AA) in oligometastatic Castrate Resistant Prostate Cancer (CRPC) patients. Trial ended in October 2022. Results already showed significant benefit in terms of biochemical response and Progression Free Survival (PFS) in the experimental arm, the trial was positive for its primary endpoint. Here we present an updated overall survival (OS) analysis. Methods: Patients affected by oligometastatic CRPC (&lt; 3 non-visceral metastatic lesions) were enrolled in the trial and randomized 1:1 to receive either AA alone (control arm) or associated with concomitant SBRT on all sites of disease (treatment arm). Kaplan-Meier survival analysis was performed to compare OS in the different arms of treatment. Results: One hundred fifty-seven patients were enrolled in ARTO trial. After a median follow up of 27 months, 29 patients died (9 vs 20 in the experimental vs control arm, respectively). Median OS was not reached in neither of the two arms of treatment, with a non-significant trend in favour of the experimental arm (p=0.07). Conclusions: After an updated follow up analysis, results confirmed good prognosis for this population of oligo-metastatic CRPC patients. First line abiraterone acetate conferred long term OS in a selected cohort of patients affected by oligometastatic disease. A positive, nonsignificant trend was found in favour of experimental arm. Considering the low number of events detected, longer follow up is needed to explore impact of upfront SBRT on OS within this randomized phase II trial. Clinical trial information: NCT03449719 .
Predictors of PSA response to Lu177-PSMA-617 in metastatic castration-resistant prostate cancer.
Authors: Rebecca Hassoun, Mark Tann, Justin Sims, Ashleigh Auxier, Sandra K. Althouse, Tareq Salous, Jennifer King, Nabil Adra
Journal: Journal of Clinical Oncology (2024)

135 Background: Lu177-PSMA-617 (Lu177) therapy is effective in a subgroup of patients with metastatic castration resistant prostate cancer (mCRPC). We evaluated PSA responses in subgroups of pts with mCRPC. Methods: Pts with mCRPC who progressed after androgen receptor pathway inhibitor (ARPI) and taxane chemotherapy (or who have refused chemotherapy) were treated with Lu177. Baseline clinical/molecular characteristics and PSMA PET parameters were analyzed and association with PSA30 and PSA50 response was evaluated. Results: 97 pts were included. Median age was 73.4 (55.9, 90.2). At baseline PSMA PET: 78 pts had PSMA + disease in bone, 61 lymph nodes, 9 lungs, 5 liver, and 1 brain. 33 pts had 1 prior ARPI, 64 pts had ≥2 prior ARPI. 13 pts had no prior taxane regimen, 42 had 1 prior taxane, 31 had 2 prior taxanes and 11 had ≥3 taxane regimens. 17 pts had prior PARP inhibitor. With a median follow-up of 6.5 months (1.38-14.54) from starting Lu177 therapy, 56 (57.7%) pts achieved a PSA30 response, and 49 (50.5%) pts achieved a PSA50 response. 59 (60.8%) pts achieved any confirmed PSA response. Grade≥3 toxicity occurred in 9 pts. Differential PSA response by subgroups is listed in the Table. Conclusions: There is a trend with higher PSA30 and PSA50 response to Lu177 with higher SUVmean, higher SUVmax, and less prior taxane exposure. [Table: see text]
Intensification of ADT with enzalutamide in high-risk patients with biochemical relapse following radical prostatectomy undergoing salvage radiation: Initial results from RTOG 3506 (STEEL).
Authors: Edwin Melencio Posadas, Hiram Alberto Gay, Joseph P Rodgers, Todd Matthew Morgan, Ying Xiao, James B. Yu, Jeff M. Michalski, Myriam Bouchard, Neil B Desai, Ryan Funk, Thomas Boike, Donald James Jurgens, Anthony C. Wong, Xinglei Shen, Lloyd T Miyawaki, Christopher S Bland, John C Hairston, Howard M. Sandler, Stephanie L Pugh, Felix Y Feng
Journal: Journal of Clinical Oncology (2024)

131 Background: Patients with high-risk features who experience biochemical relapse (BCR) after radical prostatectomy (RP) benefit from the addition of androgen deprivation therapy (ADT) to salvage radiotherapy (SRT). We hypothesized that intensification of androgen receptor (AR) blockade with enzalutamide would improve SRT outcomes for high-risk patients. Methods: Post prostatectomy prostate cancer patients who have had BCR (PSA ≥ 0.2 ng/mL) with at least 1 high-risk feature (Gleason 8-10, seminal vesicle invasion, pN1, persistent PSA &gt;0.1 ng/mL after RP, and PSA ≥ 0.7 ng/mL) were eligible. Patients were randomized 1:1 to 24 months of ADT with an LHRH analog (LHRHa) or intensified ADT comprised of LHRHa + enzalutamide. The primary endpoint was progression free survival (PFS) with progression defined as PSA ≥ 0.05 ng/mL or initiation of new therapy following SRT. The target accrual of 170 patients provided 80% power to detect a HR=0.65 using a one-sided logrank test with a type I error of 0.10. Results: Between April 2019 and August 2022, 188 patients were enrolled. The patient characteristics were well balanced between the two arms. Median age was 64 years. Nodal involvement (pN1), pT3a-b, and Gleason 9 were noted in 22%, 77%, and 52% of patients, respectively. Over 70% had &gt; 1 aggressive feature. Median follow-up time at the time of this report was 15.8 months. Prostatic fossa and pelvic SRT were mandatory. Para-aortic radiotherapy (RT), and lymph node and prostatic fossa lesion RT boosts were left at the discretion of the radiation oncologist. PFS favored the enzalutamide-intensified arm (HR=0.72, 80% confidence interval [CI]:0.56-0.94, one-sided p=0.14). Grade 3 adverse events (AEs) related to treatment in the standard versus enzalutamide arms were 11 vs. 23%, while Grade 4 AEs were 4% vs. 1%, respectively. The most common AEs (all grades, &gt;15%) included hot flashes, fatigue, diarrhea, and decreased lymphocytes. The grade 3+ AEs (&gt;3%) included decreased lymphocytes and hypertension. The largest differences (&gt;7%) in AEs included insomnia, decreased lymphocytes. Diarrhea was less frequent with enzalutamide (40% vs 54%). Conclusions: The addition of enzalutamide to standard ADT did not meaningfully increase toxicity. While there was a trend toward PFS benefit from intensification, it has not yet met statistical significance. Updates on PFS and other clinical endpoints including quality of life will be reported with longer follow-up. Clinical trial information: NCT03809000 .
Phase 1/2 trial of oral EPI-7386 (masofaniten) in combination with enzalutamide (Enz) compared to Enz alone in patients with metastatic castration-resistant prostate cancer (mCRPC): Phase 1 (P1) results and phase 2 (P2) design.
Authors: Christos Kyriakopoulos, Gurkamal S. Chatta, Andrew Leonard Laccetti, Nicholas Iannotti, Alexandra Sokolova, Sebastien J. Hotte, Ronald F. Tutrone, Mark Christopher Markowski, Luke T. Nordquist, Roberto Pili, Fred Saad, Jingsong Zhang, Karen Villaluna, Brett Younginger, Ronan Le Moigne, Alessandra Cesano
Journal: Journal of Clinical Oncology (2024)

141 Background: EPI-7386 (masofaniten) is a next-generation aniten that inhibits androgen receptor (AR) activity by binding the N-terminal domain and blocking transcription, irrespective of ligand-binding domain resistance mechanisms. Preclinically, the combination of masofaniten with Enz results in a deeper blockade of the AR pathway and greater antitumor activity than either agent alone. Methods: This is a Phase 1/2 multicenter clinical trial (NCT05075577) enrolling patients (pts) with mCRPC on androgen deprivation therapy and naïve to second-generation antiandrogens (one line of prior chemotherapy in the metastatic hormone-sensitive setting allowed). P1 examines escalating doses of masofaniten + Enz at 120 or 160 mg QD. Primary and secondary endpoints of P1 evaluate the safety and pharmacokinetics (PK) of masofaniten + Enz when co-administered to establish the recommended P2 combination doses (RP2CDs). P2 is designed as a two arm, 2:1 randomized, open-label trial evaluating the antitumor activity of masofaniten in combination with Enz versus Enz alone; approximately 120 pts will be randomized with masofaniten 600 mg BID + Enz 160 mg QD (n=80) vs single agent Enz at 160 mg QD (n = 40). Results: P1 completed enrollment with 18 pts in 4 cohorts with 16 pts evaluable for efficacy as per protocol. The combination regimen was well tolerated with a safety profile consistent with Enz monotherapy. One grade 3 rash was observed in cohort 4 evaluating masofaniten 600 mg BID + Enz 160 mg QD. PK results demonstrated Enz exposure was not impacted by concomitant administration of masofaniten, allowing testing of the full dose of Enz (160 mg). By contrast, masofaniten exposure was consistently reduced by concomitant administration of Enz (CYP3A4 inducer that metabolizes masofaniten) but remained within the clinically relevant range with the highest exposures and C min observed using masofaniten BID dosing. Although efficacy data are still maturing, to date, response rates were PSA50 88% (14/16 pts), PSA90 69% (11/16 pts) and PSA &lt;0.2 ng/mL 56% (9/16 pts) in evaluable pts, regardless of their previous chemotherapy status. Conclusions: The RP2CD for P2 was established at masofaniten 600 mg BID + Enz 160 mg QD. Updated results, including long term follow-up of the dose escalation patients, and P2 study design, will be presented. Clinical trial information: NCT05075577 .
Belzutifan versus everolimus in participants (pts) with previously treated advanced renal cell carcinoma (RCC): Patient-reported outcomes (PROs) in the phase 3 LITESPARK-005 study.
Authors: Thomas Powles, Laurence Albiges, Katriina Johanna Jalkanen, Guillermo De Velasco, Mauricio Burotto, Pooja Ghatalia, Cristina Suárez, Elaine T. Lam, Roberto Iacovelli, Mahmut Gumus, Elena Verzoni, Christian K. Kollmannsberger, Walter Michael Stadler, Balaji Venugopal, Reshma Shinde, Todd L. Saretsky, Li He, Donna Vickery, Toni K. Choueiri, Brian I. Rini
Journal: Journal of Clinical Oncology (2024)

361 Background: In the randomized, open-label, phase 3 LITESPARK-005 (NCT04195750) study, belzutifan treatment showed superior PFS (primary endpoint; HR 0.75 [95% CI 0.63–0.90]; P&lt;.001) and ORR (key secondary endpoint; estimated percentage-point difference 18.4 [95% CI 14.0–23.2]; P&lt;.00001) vs everolimus in pts with advanced/metastatic clear cell RCC that progressed after prior immune checkpoint and anti-angiogenic therapies. We present PRO findings for belzutifan vs everolimus in LITESPARK-005. Methods: PROs were evaluated by FKSI-DRS and EORTC QLQ-C30 questionnaires in all randomized pts with ≥1 dose study treatment and ≥1 completed PROs assessment, administered electronically on d 1 of wk 1, 3, 5, and 9, Q4W thereafter, at treatment discontinuation, and d 30 after last dose. Time to deterioration (TTD) and least square (LS) mean change from baseline as measured by FKSI-DRS and QLQ-C30 global health status/quality of life (GHS/QoL) and physical functioning (PF) scales were prespecified as secondary endpoints. PROs were not formally statistically tested and 95% CI and P-values were nominal and descriptive. Results: As of June 13, 2023 (data cutoff date at second prespecified interim analysis), median (range) follow-up was 25.7 mo (16.8–39.1). Median (range) duration of treatment was 7.6 mo (0.1–35.8) with belzutifan vs 3.9 mo (0.0–33.2) with everolimus; 84 (22.6%) vs 18 (5.0%) pts remained on treatment. 366 of 374 pts randomized to belzutifan and 354 of 372 pts randomized to everolimus were included in the PRO analysis population. Completion rates for FKSI-DRS and QLQ-C30 were &gt;90% at baseline and &gt;55% at wk 17 (~4 mo) in each arm. Meaningfully longer TTD in FKSI-DRS and QLQ-C30 GHS/QoL scores were observed for belzutifan vs everolimus (Table). LS mean changes in FKSI-DRS and QLQ-C30 GHS/QoL scores suggested stability from baseline to wk 17 with belzutifan vs worsening with everolimus, and a potential greater worsening in PF scores with everolimus vs belzutifan. Conclusions: Belzutifan was associated with prolonged TTD in FKSI-DRS and EORTC QLQ-C30. Score changes from baseline to wk 17 also favored belzutifan over everolimus. Overall, PRO results indicate better disease-specific symptoms and quality of life among pts treated with belzutifan compared with everolimus. Clinical trial information: NCT04195750 .[Table: see text]
(ARTO trial-NCT03449719): Role of local treatment after progression in patients with castrate-resistant prostate cancer undergoing first-line abiraterone treatment.
Authors: Giulio Francolini, Vanessa Di Cataldo, Beatrice Detti, Pietro Garlatti, Saverio Caini, Alessio Bruni, Gianluca Ingrosso, Rolando Maria D'Angelillo, Anna Rita Alitto, Matteo Augugliaro, Luca Triggiani, Silvana Parisi, Gaetano Facchini, Marco Banini, Gabriele Simontacchi, Isacco Desideri, Icro Meattini, Richard K. Valicenti, Lorenzo Livi
Journal: Journal of Clinical Oncology (2024)

130 Background: ARTO (NCT03449719) is a multicentre, randomized phase II trial testing the benefit of concomitant stereotactic body radiation therapy (SBRT) and abiraterone acetate (AA)+ prednisone administration in oligometastatic Castrate Resistant Prostate Cancer (CRPC) patients. Results already showed significant benefit in terms of biochemical response and Progression Free Survival (PFS) in the experimental arm. To explore role of local treatment throughout the whole clinical history of these patients, here is reported a subgroup analysis focusing on impact of treatment (SBRT vs second line systemic therapy) after progression. Methods: Patients affected by oligometastatic CRPC (&lt;/= 3 non-visceral metastatic lesions) were enrolled in the trial and randomized 1:1 to receive either AA+ prednisone alone (control arm) or associated with concomitant SBRT on all sites of disease (treatment arm). PFS2 was defined as time between first progression event and second progression, death or last follow up. Cox regression analysis was performed to compare PFS2 in patients treated with SBRT on oligo-progressive metastatic sites vs patients undergoing second line systemic therapy (primarily taxane chemotherapy). Results: One hundred fifty-seven patients were enrolled in ARTO trial. At last follow up (August 2023), 77 patients progressed after abiraterone+ prednisone treatment (23 vs 54 in the experimental vs control arm, respectively). Of these, 14 received best supportive care and were excluded from the analysis, 23 underwent SBRT on oligo-progressive metastatic sites (17 and 6 originally randomized to the experimental vs control arm, respectively), 40 were treated with second line systemic treatment. A second progression event was detected in 14 patients. Median PFS 2 was 10 months (95% CI 10-17) and 10 months (95% CI 7-12) for patients undergoing SBRT vs second line treatment, respectively (HR 1.26, 95% CI 0.33-4.75, p 0.73). Conclusions: When oligoprogressive status is detected, SBRT may achieve similar benefit if compared to second line systemic treatment. These data, in the context of a randomized trial with positive results for primary endpoints, suggest that repeated SBRT may be a viable treatment option in selected patients. Clinical trial information: NCT03449719 .
Stockholm3 validation in a multi-ethnic cohort for prostate cancer (SEPTA) detection: A multicentered, prospective trial.
Authors: Hari Thambiah Vigneswaran, Martin Eklund, Andrea Discacciati, Tobias Nordström, Rebecca A. Hubbard, Nathan Perlis, Michael Abern, Daniel Moreira, Scott E. Eggener, Paul M. Yonover, Alexander Chow, Kara Watts, Michael A. Liss, Gregory R Thoreson, Andre Luis Abreu, Geoffrey A Sonn, Thorgerdur Palsdottir, Fredrik Wiklund, Henrik Gronberg, Adam B Murphy
Journal: Journal of Clinical Oncology (2024)

262 Background: Stockholm3 is a multiparametric blood test incorporating germline risk, proteins and clinical data which improves prostate cancer (PC) risk stratification compared to PSA, however no validation exists in an ethnically diverse population. Methods: SEPTA is a prospective trial (NCT04583072) aimed to validate Stockholm3 in an ethnically diverse cohort of men referred for prostate biopsy at 17 North American sites from 2019 to 2023 (supplemented with bio-banked specimens 2008-2020). The trial had two prespecified primary aims when comparing Stockholm3 (≥15) compared to PSA (≥4 ng/ml): (1) Demonstrate non-inferior sensitivity in detecting clinically significant PC (csPC) (defined as ISUP Gleason Grade group ≥2) compared to PSA (non-inferiority margin of 20%). (2) Prove superior specificity thereby reducing the number of biopsies compared to PSA in men with benign or ISUP 1 biopsies. Both aims were assessed using a one-sided alpha of 0.025. A secondary aim was to evaluate Stockholm3 and PSA across ethnic subgroups. Statistical analysis plans were published before the analysis commenced. Results: The study involved 2,129 biopsied participants, categorized into self-identified groups: African American/Black (24%), White/Caucasian (46%), Hispanic/Latino (14%), and Asian (16%). Median participant age was 63 years. PSA and Stockholm3 median values were 6.1 ng/mL and 17, respectively. A total of 16% underwent MRI-targeted biopsies and 20% had a prior benign biopsy. On either systematic or targeted biopsy, csPC was found in 29%, 14% had ISUP 1 cancer, and 57% benign. The detection rate for csPC across groups were: African American/Black (37%), White/Caucasian (28%), Hispanic/Latino (29%), and Asian (21%). Overall, Stockholm3≥15 showed non-inferior sensitivity compared to PSA≥4 ng/ml (relative sensitivity: 0.95 [95% CI: 0.92-0.99]) and nearly 3 times superior specificity (relative specificity: 2.91 [95% CI: 2.63-3.22]). Results were consistent across ethnic subgroups: non-inferior sensitivity (0.91-0.98) and superior specificity (2.51-4.70). Stockholm3 ≥15 would have reduced benign and ISUP 1 biopsies by 45% overall and between 42-52% across ethnic subgroups compared to PSA ≥4 ng/ml. Stockholm3 exhibited higher AUC (0.82) compared to PSA (0.66), with similar trends in ethnic subgroups. Conclusions: In an ethnically diverse population, Stockholm3 would significantly reduce unnecessary prostate biopsies and diagnosis of ISUP 1 cancer at a similar sensitivity of PSA for detecting clinically significant cancer. Clinical trial information: NCT04583072 . [Table: see text]