tbuckley/cabot-search huggingface dataset:
Apalutamide and stereotactic body radiation therapy for low-burden, metastatic, hormone-sensitive prostate cancer: A randomized trial (PERSIAN).
Authors: Giulio Francolini, Angelo Porreca, Gaetano Facchini, Daniele Santini, Alessio Bruni, Nicola Simoni, Marco Trovò, Mattia Falchetto Osti, Giuseppe Fornarini, Michele Sisani, Vanessa Di Cataldo, Beatrice Detti, Pietro Garlatti, Niccolò Bertini, Luca Burchini, Giulio Frosini, Ilaria Bonaparte, Sergio Serni, Andrea Minervini, Lorenzo Livi
Journal: Journal of Clinical Oncology (2024)

TPS235 Background: TITAN trial showed that apalutamide + ADT improved OS in patients with metastatic hormone sensitive prostate cancer (mHSPC), both in low and high-volume disease. On the other hand, SABR-COMET trial suggested that stereotactic body radiotherapy (SBRT) improved outcomes in oligometastatic patients if compared to systemic therapy alone. Recently, one trial suggested that SBRT may offer significant benefit in terms of biochemical response and progression free survival within oligometastatic castrate resistant prostate cancer patients undergoing first line abiraterone acetate treatment (ARTO trial, NCT03449719). However, there are no data specifically assessing the benefit offered by SBRT in oligometastatic mHSPC treated with apalutamide. PERSIAN trial is aimed to test the hypothesis that metastases directed SBRT will improve outcomes in select subgroups of pts with oligometastatic mHSPC treated with apalutamide + ADT. Moreover, we implemented baseline blood sample tests at enrollment/randomization, to evaluate the status of PIK3CA/AKT1/PTEN and BRCA1/BRCA2 mutations, and to investigate the predictive value of these alterations on treatment response. Furthermore, oncometabolites expression will be evaluated through metabolomic analysis before and after start of SBRT. Methods: PERSIAN trial is a prospective phase II randomized superiority study. All patients are affected by metachronous oligometastatic HSPC defined as presence of &lt; 5 non-visceral metastatic lesions. Patients with de novo metastatic disease are excluded from the trial. Patients will be randomized to receive standard systemic treatment alone with apalutamide + ADT (Arm A: Control) or the same systemic treatment combined with SBRT on all sites of metastatic spread (Arm B: Treatment). This trial design will allow us to evaluate the benefit of SBRT in a selected cohort of patients with identical systemic treatments. Primary endpoint of the trial is the rate of patients with complete biochemical response (PSA &lt; 0.2 ng/ml) 6 months after apalutamide + ADT start. Assuming a rate of complete biochemical response of 61% in the control arm, a sample size of 180 patients will have 80% statistical power to detect an absolute benefit of 19% in the treatment group, with alpha 0.05. Secondary endpoints are: time to PSA progression, radiologic progression free survival, frequency of treatment severe adverse events, overall and cancer specific survival, quality of life (measured with EORTC QLQ-C30 and EORTC QLQ-PR25 questionnaires). Enrollment started in March 2023, 31 patients have been enrolled to date. Clinical trial information: NCT05717660 .
A novel blood-based mRNA genomic test for screening, early detection, prognosis, and monitoring of prostate cancer: A multicenter study.
Authors: Yutaka Hashimoto, Shiv Verma, Guoren Deng, Dharam P Chauhan, Sujit Nair, Hirofumi Yoshino, Junya Arima, Yutong Liu, Koji Hatano, Yogesh Shivakumar, Raghunath S. Krishnappa, Chitra Chandran, Narasimhan Ragavan, Hideki Enokida, Norio Nonomura, K C Balaji, Sudhir K Rawal, Ashutosh K. Tewari, Rajvir Dahiya, Sanjay Gupta
Journal: Journal of Clinical Oncology (2024)

271 Background: Current screening tools, including prostate-specific antigen (PSA) and clinicopathologic parameters, have limitations in the diagnosis and prognosis of prostate cancer. This study examined whether genomic biomarkers can improve screening and monitoring of prostate cancer. Methods: We identified a panel of 25 prostate cancer-related genes through rigorous bioinformatics, computational analyses and genetic testing. These tests, developed by Geneverify Inc. (Hayward, CA; U.S. patent # 10801072 and 10822661) were utilized and optimized by qRT-PCR to determine the diagnostic and prognostic ability of prostate cancer using blood and tissues. The log2-fold increase in gene expression was used to assign the risk score to individual patients. ROC (receiver operator characteristic), AUC (area under ROC curve), and calibration curves were generated to display the overall performance and discrimination ability to separate cancer and non-cancer specimens. Results: A total of 419 prostate cancer patients (135 blood and 284 tissue samples) and 130 normal samples were analyzed in this study. The eligibility criteria were to collect blood and surgical specimens from patients with prostate cancer from 9 hospitals. The study endpoints were to analyze mRNA genomic profiling and correlate with clinicopathologic parameters of the patients. In the blood, a 25-panel gene-set separated prostate cancer patients (n=135) from non-cancer (n=30), AUC = 0.906 [sensitivity = 90% and specificity = 91%]. Assessment of tissue specimens from benign (n=100) and cancer patients (n=284) showed similar results with AUC = 0.9514 [sensitivity = 95% and specificity = 94%]. Interestingly, patients with Gleason grades (GS) &gt;7 showed higher expression of these genes compared to GS &lt;7, suggesting the prognostic ability of the gene-set. When we compared the gene expression in blood verses tissues, there were similar patterns, suggesting that blood can be used for screening, diagnosis and risk assessment of prostate cancer. Conclusions: To our knowledge, this is the first study to investigate the role of mRNA-based genomic signatures for screening, early diagnosis and prognosis of prostate cancer using blood samples. Our data suggest that blood mRNA-genomic profiling developed by Geneverify has the ability to diagnose prostate cancer and stratify patients into distinct prognostic groups, which in turn help in making better treatment strategies.
CaboLu: A phase 1b study of cabozantinib (cabo) in combination with lutetium (Lu 177) vipivotide tetraxetan (LVT) in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC).
Authors: Gliceida Galarza Fortuna, Colin Moynier, Kenneth M. Boucher, Blake Nordblad, Matthew Covington, Gabriel Fine, Susan Clement, Michelle Esplin, Manish Kohli, Sumati Gupta, Benjamin L. Maughan, Neeraj Agarwal, Umang Swami
Journal: Journal of Clinical Oncology (2024)

TPS251 Background: LVT is a β-emitting radioligand approved for pts with prostate-specific membrane antigen (PSMA)-positive mCRPC with prior treatment with androgen receptor pathway inhibitor (ARPI) and taxane-based chemotherapy. However, in the VISION trial, 50% of pts with measurable disease didn’t respond (PMID: 34161051). Prior studies have shown a significant correlation between PSMA and VEGF expression (p&lt;0.001) in LNCaP tumors and locally recurrent PCa after radiotherapy. Cabo is an oral, small-molecule tyrosine kinase inhibitor with potent activity against multiple receptor tyrosine kinases including VEGFR2. Therefore, the combination of cabo with LVT may be synergistic. We initiated a phase 1b dose-scalation study of cabo in combination with standard of care (SOC) LVT in pts with mCRPC. Methods: This is an IRB-approved, investigator-initiated, single-arm, single-center, dose-escalation (DEsc) and dose-expansion (DExp) study. The primary hypothesis is that Cabo+LVT will be safe and effective in mCRPC pts. Key inclusion criteria: ≥18 years of age, mCRPC with histologically/cytologically confirmed adenocarcinoma without small cell histology, ECOG performance status ≤2, prior treatment with ≥2 cycles of taxane and at least 1 ARPI, adequate organ function and eligible for SOC LVT. Key exclusion criteria: Prior treatment with cabo or PSMA-targeted radioligand therapy. DEsc part will follow traditional 3+3 design to evaluate SOC LVT in combination with 3 dose levels (DL) of daily oral cabo: 40 mg (DL 1), 60 mg (DL 2) and 20 mg (DL -1). Primary objective: to determine maximal tolerated dose (MTD), and recommended dose and schedule for DExp phase. Secondary objective: To assess safety and tolerability of cabo with LVT. Expected enrollment 9 pts (range 4-18). DExp part will enroll 24 evaluable pts. Primary objective: to evaluate preliminary efficacy by estimating the progression-free survival (PFS) at 24 weeks (PFS 24w ) as assessed by PCWG3-modified RECIST v1.1. 2-sided 80% and 60% confidence intervals will be constructed for PFS 24w via exponential Greenwood’s formula for Kaplan-Meier survival estimate, providing 90% and 80% 1-sided confidence for 30 pts at DExp dose (6 DEsc+24 DExp). Secondary objective: (1) To assess safety and tolerability cabo+LVT (2) assess objective response rate, duration of response, radiographic PFS, PFS at 38 weeks, PSA PFS, PSA 50% response rate, and OS. 1 patient has been enrolled. Clinical trial information: NCT05613894 .
Treatment-free survival after first-line therapies for metastatic renal cell carcinoma: An International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) analysis.
Authors: Mehul Gupta, Connor Wells, Meredith M. Regan, Wanling Xie, Vishal Navani, Renee Maria Saliby, Naveen S. Basappa, Frede Donskov, Takeshi Yuasa, Kosuke null Takemura, Christian K. Kollmannsberger, Megan Crumbaker, Aly-Khan A. Lalani, Thomas Powles, Sumanta Kumar Pal, Rana R. McKay, Jae-Lyun Lee, Ravindran Kanesvaran, Toni K. Choueiri, Daniel Yick Chin Heng
Journal: Journal of Clinical Oncology (2024)

390 Background: Patients treated with immune checkpoint blockade (ICB) may experience disease control without need for ongoing systemic therapy, a period not well described by conventional time-to-event endpoints. Treatment-free survival (TFS) represents a novel endpoint to quantify this period. Methods: We identified patients with mRCC from the IMDC dataset initiating first-line systemic therapy with VEGFR monotherapy (sunitinib, pazopanib), combination ICB-VEGFR therapy ([axitinib or envatinib]-pembrolizumab, cabozantinib-nivolumab, axitinib-avelumab), or ICB doublet therapy (ipilimumab-nivolumab) between February 1, 2014, and February 1, 2023. Overall survival from treatment initiation was partitioned into periods including TFS, time on first-line therapy, and survival after subsequent therapy initiation utilizing differences in restricted mean survival time (RMST) over 36-months. TFS was defined as the difference between the 36-month RMST between: (1) time from treatment initiation to discontinuation of first-line therapy, death, or censor at last follow-up and (2) time from treatment initiation to subsequent therapy initiation, death, or censor at last follow-up. Results: 3,758 patients with mRCC initiated first-line VEGFR monotherapy (n=2,635; median age 62 years; 19.1% IMDC favourable risk), ICB-VEGFR regimens (n=354; median age 60 years; 33.3% IMDC favourable risk), or doublet ICB (n=769; median age 62 years; 0% IMDC favourable risk). Patients with favourable IMDC risk initiating VEGFR monotherapy and ICB-VEGFR regimens experienced a TFS duration of 8.5% (3.1 mos 95% CI 1.5 - 4.6) and 10.1% (3.7 mos 95% CI 0.2-7.2) of the 36-month period respectively. Among intermediate/poor risk patients, those treated with VEGFR monotherapy, ICB-VEGFR regimens, and ICB doublet therapy experienced 5.9% (2.1 mos 95% CI 1.4 - 2.8), 10.3% (4.7 mos 95% CI 1.0-6.4), and 14.6% (5.3 mos 95% CI 3.8-6.8) of the 36-month period alive and treatment free respectively. Conclusions: Patients receiving VEGFR monotherapy or ICB-VEGFR combination therapies spent at most 10% of the 36-month period surviving treatment free, while IMDC intermediate/poor risk patients treated with ICB doublet therapy experienced a TFS period of 15% of the 36-month period.[Table: see text]
A randomized phase I/II study of neoadjuvant treatment with <sup>177</sup>-Lutetium-PSMA-617 with or without ipilimumab in patients with very high-risk prostate cancer who are candidates for radical prostatectomy (NEPI trial).
Authors: Ulrich Krafft, Viktor Grünwald, Wolfgang P. Fendler, Ken Herrmann, Henning Reis, Florian Roghmann, Kambiz Rahbar, Axel Heidenreich, Frederik Giesel, Guenter Niegisch, Boris A. Hadaschik
Journal: Journal of Clinical Oncology (2024)

TPS352 Background: High-risk prostate cancer accounts for approximately 15% of newly diagnosed prostate cancers. For patients with high-risk, locally advanced prostate cancer, prostatectomy alone may be insufficient therapy. Cure rates from radical prostatectomy alone are less than 25%. Ipilimumab increases overall survival in men with post-docetaxel mCRPC who received radiotherapy to bone metastases followed by ipilimumab in comparison to placebo. Final results of the VISION trial (NCT03511664), a phase III study designed to assess the efficacy of [ 177 Lu]Lu-PSMA-617 in patients with PSMA-positive mCRPC, show a significant prolongation of survival in a setting without established therapy. Since both ipilimumab combined with radiation and [ 177 Lu]Lu-PSMA-617 have been proven to be effective in the treatment of mCRPC, we hypothesize, that CTLA-4-inhibitors exert synergistic effects on [ 177 Lu]Lu-PSMA-617 RLT-induced tumor damage and immune priming. Methods: Patients diagnosed with highest risk prostate cancer (ISUP-GG 4+5 and cT3 plus cN+ or PSA &gt; 20ng/ml) who are candidates for radical prostatectomy receive 12 weeks of neoadjuvant treatment with ADT plus [ 177 Lu]Lu-PSMA-617 (LuPSMA) with randomized allocation with or without ipilimumab. Prior to initiation of the randomized set, we will conduct a Safety-Run-In-Phase. The initial 3-6 patients will receive a reduced dose of 3.7 Gb [ 177 Lu]Lu-PSMA-617 and 3 mg/kg Ipilimumab, which will be increased to the target dose of 7.4Gb [ 177 Lu]Lu-PSMA-617 and 3 mg/kg Ipilimumab in the following 3-6 patients if sufficiently well tolerated. The safety and feasibility of the combination will be assessed after 6-12 patients based on toxicity or delay of prostatectomy (max. 3 weeks). In the absence of serious toxicity signals a total of 46 patients will be randomized 1:1 (ipilimumab + ADT + LuPSMA vs. ADT + LuPSMA) to receive 2 cycles of 7.4 GBq LuPSMA with or without 4 cycles of ipilimumab 3mg/kg prior to prostatectomy. Scheduled Imaging with mpMRI and PSMA PET CT is performed prior to neoadjuvant therapy and prior to radical prostatectomy. Co-primary endpoints of the study are feasibility of radical prostatectomy after neoadjuvant therapy, and complete pathologic response. Secondary endpoints are evaluation of the safety profile of neoadjuvant treatment according to "National Cancer Institute Common Terminology Criteria for Adverse Events" (NCI CTCAE) v5.0 and disease-free survival. Enrollment of the first patient in NEPI Trial is expected to be completed in late September 2023. A total of up to 3 German centers will participate. Clinical trial information: EudraCT-Nr.: 2021-004894-30.
Ipilimumab/nivolumab (I/N) compared to axitinib/pembrolizumab (A/P) in metastatic renal cell carcinoma (mRCC): Insights from a Canadian population.
Authors: Hyejee Ohm, Sunita Ghosh, Mehul Gupta, Lori Wood, Vincent Castonguay, Jeffrey Graham, Christian K. Kollmannsberger, Dominick Bosse, Denis Soulieres, Daniel Yick Chin Heng, Nazanin Fallah-Rad, Antonio Finelli, Simon Tanguay, Aly-Khan A. Lalani, Bimal Bhindi, Georg A. Bjarnason, Rodney H. Breau, Frederic Pouliot, Naveen S. Basappa
Journal: Journal of Clinical Oncology (2024)

393 Background: First-line treatment for mRCC includes I/N and A/P. These two regimens have not been compared in a randomized clinical trial as both CM-214 and KN-426 used single-agent tyrosine kinase inhibitors (TKIs) as the comparator. Meta-analyses suggest improved efficacy outcomes with A/P, but increased likelihood of complete response with I/N. We compared these treatments in the real-world. Methods: Data of consented mRCC patients with clear cell histology from the Canadian Kidney Cancer information system (CKCis) was obtained from January 2013 to December 2021. Treatment outcomes adjusting for age including overall survival (OS), progression free survival (PFS), and response rate (RR) for all patients and intermediate-poor risk patients were completed. Chi-square tests compared the frequency of side effects. Results: Among 547 patients, 360 received I/N and 187 received A/P. Median follow-up was 30.0 (0.1-112.1) months. Median duration of treatment was 6.9 (0.0-68.4) months for I/N and 20.2 (0.1-72.4) months for A/P. Intermediate-poor risk patients were higher in the I/N compared to A/P cohort (91.9% vs. 66.2%; p&lt;0.0001). Cox regression for OS showed no difference between I/N compared to A/P (aHR 1.1, 95% CI [0.77-1.58], p=0.61). PFS showed no statistical difference but a trend for worse with I/N at 12.1 months compared to 22.3 months for A/P (aHR=1.2, 95% CI [0.95-1.62], p=0.11). RR was 40.9% with I/N compared to 56.0% in A/P (aOR 0.52, 95%CI [0.33-0.83], p=0.005). Subgroup analyses for the intermediate-poor risk mRCC patients showed no differences in OS (aHR 0.95, 95%CI [0.65-1.38], p=0.79) and PFS (aHR 1.21, 95%CI [0.90-1.62], p=0.21) between treatment groups but improved RR (aOR 0.58, 95%CI [0.35-0.96], p=0.06) with A/P. 61.7% of I/N patients compared to 79.1% of A/P suffered adverse events that led to a dose or schedule change (p&lt;0.001). Most common toxicities for both groups include diarrhea, fatigue, transaminitis, rash, and anorexia. Conclusions: There was no difference in OS between mRCC patients treated with I/N compared to A/P. A/P demonstrates improved RR and a trend towards longer PFS at the expense of increased frequency of side effects. Despite a median follow-up of 30 months, the data is limited by a high amount of censoring.[Table: see text]
PSA flare in patients with metastatic castration-resistant prostate cancer undergoing <sup>177</sup>Lu-PSMA treatment.
Authors: Haoran Li, Elizabeth Marie Wulff-Burchfield, Saqib Abbasi, Arshit Narang, Emre Dal, Joseph Donald, Wendell Y Yap, Xinglei Shen, Ronald C. Chen, Rahul Atul Parikh
Journal: Journal of Clinical Oncology (2024)

157 Background: 177Lu-PSMA (Lu-177) is an FDA-approved radiopharmaceutical agent for metastatic castration-resistant prostate cancer (mCRPC) progressed on prior chemotherapy and androgen receptor pathway inhibitor. The chronology, frequency and association PSA flare with Lu-177 on overall treatment outcome is unclear. Our retrospective study evaluates the association of PSA flare with clinical outcomes in mCRPC patients undergoing Lu-177 therapy. Methods: A retrospective study was conducted from 4/2022-8/2023 for patients treated with Lu-177 at the University of Kansas Cancer Center. PSA flare was defined as an initial rise in PSA levels that subsequently declined. A bone flare is defined as increased radiotracer uptake in bone scans. The primary outcome was progression-free survival (PFS). The secondary outcomes included overall survival (OS), PSA response, disease control rate (DCR) and safety. Results: A total of 46 patients were included in this study. The median age was 73 years (range: 52-100). Of these, 14 patients (30.4%) had completed 6 cycles of treatment. The median number Lu-177 cycles received was 3 (range: 1-6). PSA flare was observed in 7 patients (15.2%), and all of the PSA flare occurred in the first cycle. The median time from the start of treatment to the onset of PSA flare was 2 weeks (range: 1-4). The median change in PSA from baseline to flare increased by 41% (range: 22-1133%). The median time from PSA flare to PSA nadir was 12 weeks (range: 9-30). The median change in PSA from flare to nadir decreased by 73% (range: 57-95%). Bone flare was seen in 4 patients (13.8%) and the median onset time is 12 weeks (range: 10-17). There was no significant difference in PFS and OS between patients with or without PSA flare [median PFS: 7.1 vs. not reached (NR), p=0.11; median OS: NR vs. NR, p=0.27). A total of 22 patients (56.4%) exhibited a 50% PSA decrease (PSA 50). The proportion of patients with PSA 50 response was similar in both the PSA flare group (57.1%) and the non-PSA flare group (56.3%) (p=0.97). Among the patients who underwent radiographic assessment (n=29), the DCR was achieved in 66.7% vs. 60.9% of patients with or without PSA flare (p=0.79). The most common side effects in patients with or without flare included fatigue (71.4% vs. 66.7%, p=0.81), arthralgia (0% vs. 26.7, p=0.31), nausea (14.3% vs. 20%, p=0.73), diarrhea (28.6% vs. 10%, p=0.20), and anorexia (28.6% vs. 10%, p=0.20). Conclusions: PSA flare in patients treated with Lu-177 is not uncommon. Our study suggests the clinical response appears consistent regardless of the flare. Further studies and additional long-term follow-up are needed to validate our findings.
Real-world metastatic renal cell carcinoma (mRCC) treatment trends in Mexico: A public vs private sector analysis.
Authors: Iván Romarico González Espinoza, Lizbett Vanessa Garcia Montes, Osvaldo Hernandez Flores, Yuly Andrea Remolina Bonilla, Luis Arturo Sanchez-Trujillo, Maria del Socorro Isabel Rios Mercado, Diana Jaimes
Journal: Journal of Clinical Oncology (2024)

397 Background: Metastatic renal cell carcinoma (mRCC) treatment avenues have expanded, yet Mexico’s fragmented healthcare system could impact real-world setting, scarce information is available, and little is known regarding this issue. This study aims to characterize the treatment patterns for mRCC in Mexico’s public and private healthcare sectors. Methods: De-identified patient data collected from 180 oncologists (03/2022 to 02/2023) using Evidera LiveTracker were assessed. Data from adult mRCC patients outside clinical study protocols were included. Patients were categorized by healthcare sectors, and line of treatment (L). A descriptive analysis was conducted. Results: Of 651 patients, 182 (28.0%) were favorable risk-stratified, 332 (51.0%) intermediate, and 137 (20.0%) high-risk. Treatment in 1L involved 542 (83.3%), 96 (14.7%) in 2L and 13 (2.0%) ≥3L. Sectors were evenly split: 327 (50.2%) public and 324 (49.8%) private. Among patients in 1L, 60.7% underwent TKI monotherapy (72.8% public vs 48.1% private) mainly with sunitinib (49.8%) and pazopanib (20.9%). Immunotherapy (IO) combination IO+IO was indicated in 26.2% (17.0% public vs 35.7% private), and IO+TKI in 7.9% (5.4% public vs 10.5% private). similar disparities trends were observed in 2L, where TKI monotherapy increased to 70.8% (84.5% public vs 58.8% private), whereas 21.9% (13.3% public vs 29.4% private) and 4.2% (2.2% public vs 5.9% private) received IO monotherapy and IO+TKI, respectively (Table). Conclusions: Despite clinical practice guidelines favoring the use of IO for mRCC 1L treatment, many Mexican patients receive currently TKI monotherapy, particularly in public healthcare, and this is consistent in subsequent lines of treatment. Potential access barriers warrant further exploration. [Table: see text]