tbuckley/cabot-search huggingface dataset:
A phase 2 study of cabozantinib in combination with atezolizumab as neoadjuvant treatment for muscle-invasive bladder cancer, (HCRN GU18-343) ABATE study.
Authors: Deepak Kilari, Aniko Szabo, Kathryn Bylow, Ariel Ann Nelson, Peter Langenstroer, Scott Johnson, Arjun Sivaraman, Kenneth Jacobsohn, Chunkit Fung, Sindhuja G Kadambi, Brian I. Rini, Melissa A Reimers, Robert S. Alter, Asit KR Paul, Brendan John Guercio, Matthew I. Milowsky
Journal: Journal of Clinical Oncology (2025)

800 Background: Atezolizumab (A) has demonstrated single agent activity as neoadjuvant therapy (NAT) for muscle invasive urothelial carcinoma (MIUC) (ABACUS trial). Cabozantinib (C) has a unique immunomodulatory profile that may foster anti-tumor immunity and has demonstrated clinical activity as monotherapy and in combination with A. We hypothesized that the combination of C and A as NAT for MIUC would improve pathologic response rate (pRR) compared to single-agent A. Methods: This open-label, single arm, multi-center study investigated the efficacy and safety of C 40 mg PO daily with A 1200mg every 3 weeks for 9 weeks as NAT for cT2-T4aN0/xM0 MIUC. Eligibility required patients (pts) to be cisplatin-ineligible or decline cisplatin, with UC as the predominant histology (≥ 50%). Primary endpoint was pRR defined as no residual muscle-invasive cancer in the surgical specimen (&lt; ypT2); patients with progression prior to cystectomy were counted as non-responders. pRR was to be compared to the 39% response rate with the single agent A using a Bayesian evaluation with a Beta (0.5, 0.5) prior. Secondary endpoints were safety and toxicity, pathologic complete response rate (pCR, ypT0N0M0) and event-free survival (EFS). Exploratory end points included patient-reported outcomes and outcome associations with biomarkers. Results: From Feb 2021 to July 2024, 46 pts enrolled at 5 sites. 2 pts were deemed ineligible, and 6 pts did not proceed with cystectomy for reasons other than progression (4 pts opted for bladder preservation, 1 pt died from causes unrelated to tx and 1 pt still undergoing tx). Median follow up is 14 mo. At study entry median age was 71 yrs, 21% were female, 98% Caucasian and 71% were cisplatin ineligible, with T2, T3 and T4 disease in 73%, 18% and 9% respectively. Histology included pure urothelial cancer (56%), squamous (18%), glandular (3%), micropapillary (18%) and plasmacytoid (5%) differentiation. Among 35 pts who underwent cystectomy, 32 (91%) / 3 (9%) completed 3 and 2 doses of A and 15 (43%) / 32 (91%) completed 9 and at least 6 weeks of C. Adverse events are being analyzed. The estimated pRR was 29.5% (95% CrI 16.5% - 44.5%) and the pCR was 20.8% (95% CrI 9.4% - 35.3%). The pCR was lower in pts with variant histology compared to pure UC (13 vs 25%; p=0.39). 2-year EFS was 68.4% (95% CI, 47.7-82.3%). Conclusions: C+A has modest activity as NAT in MIUC and did not meet the pre-specified primary endpoint for pRR. Biomarkers studies are planned. Clinical trial information: NCT04289779 .
Concurrent pembrozulimab and radiation treatments in the management of locally advanced bladder cancer in cisplatin-ineligible patients.
Authors: Niraj K. Gupta, Robert H. Liebross, Jainie Clark, Aneesh Gupta, Christopher Leagre, Scott Pike, Thomas Dugan, Kenneth Ney, Markus Fitzik, Vasu Tumati
Journal: Journal of Clinical Oncology (2025)

817 Background: Pembrolizumab (P) is commonly used to treat cisplatin-ineligible patients with locally advanced bladder cancer. We previously reported a potential synergistic effect of concurrent radiation and immunotherapy, https://doi.org/10.1200JCO.2020.38.15_suppl.e17020. Here, we present our updated experience with this combination. Methods: After transurethral resection of bladder tumor (TURBT), patients received Pembrolizumab 200 mg IV every 3 weeks and radiation treatments, starting 1 week after Pembrolizumab initiation. A total of 64-65 Gy was delivered to the bladder and pelvis. Pembrolizumab was continued for 1 year. Response was assessed by follow-up cystoscopies and serial imaging studies. Results: Between October 2021 and May 2023, 14 patients with locally advanced bladder cancer (cT2-T4 or LN+ve) were treated. Median age was 74 years (range 62-91), with a male-to-female ratio of 9:5. ECOG performance status was 0-1 in 5 patients, 2 in 7 patients, and 3 in 2 patients. All patients completed radiation treatments, while 10 patients completed 1 year of Pembrolizumab, 3 patients completed 6-12 months, and 1 patient received less than 6 months. Follow-up cystoscopy was performed in 12 patients, with 7 (58.3%) showing a complete clinical response. Grade 3/4 immune-related adverse events (irAEs) occurred in 1 patient. At a median follow-up of 16 months (range 6-23 months), 9/14 patients (64.2%) remained without evidence of distant disease, 3/14 patients (21.4%) had oligometastatic disease treated with stereotactic body radiation therapy (SBRT) and are now without distant disease, and 2/14 patients (14.4%) developed multiple distant metastases. Conclusions: Concurrent radiation and immunotherapy is an effective option with a favorable side-effect profile for cisplatin-ineligible patients with locally advanced bladder cancer. Incorporating other non-chemotherapeutic agents, such as antibody-drug conjugates, into concurrent radiation-immunotherapy combinations warrants further investigation.
First-in-human phase 0 safety, imaging, pharmacokinetics, and dosimetry study of <sup>64</sup> Cu-PD-32766, a carbonic anhydrase IX (CAIX)-targeting peptide, in patients with clear cell renal cell carcinoma (ccRCC).
Authors: Toshihiro Horii, Mitsuyoshi Yoshimoto, Akinori Kobayashi, Chihiro Kondo, Nobuaki Matsubara, Chikako Funasaka, Hiromichi Nakajima, Yasutoshi Kuboki, Kimiteru Ito, Masato Murakami, Shoko Ito, Tomoaki Higuchi, Naoki Kanazawa, Yuichi Funase, Daisuke Kano, Akira Inagaki, Saeko Mochinaga, Hikari Inagawa, Tatsushi Kobayashi, Anri Inaki
Journal: Journal of Clinical Oncology (2025)

TPS605 Background: Carbonic Anhydrase (CA)IX is a type of carbonic anhydrase and is expected to be a useful target for detecting tumors with poor prognosis. Particularly in clear cell renal cell carcinoma, high CAIX expression has been reported in a large proportion of patients. In this study, we developed a novel radioligand agent called PD-32766 that specifically binds to CAIX and administered it to recurrent cases of clear cell renal cell carcinoma (ccRCC) patient. Safety, imaging, pharmacokinetics and dosimetry are evaluated. Methods: Between May 2024 and September 2024, PD-32766 labeled by positron-emitting 64Cu (64Cu-PD-32766) was intravenously administered at a dose of 148 MBq (±20%) to five patients with clear cell renal cell carcinoma who had either distant metastasis or local recurrence, and who met other eligibility criteria. PET/CT imaging was performed at 5, 60, 120, 240 minutes, 24, and 48 hours after administration, with vital signs, blood tests, and urinalysis performed as needed. The primary endpoint was the patient-level PET uptake positivity rate of target tumor regions. Secondary endpoints included the number of positive lesions, pharmacokinetics, estimated radiation dose, and the frequency and types of adverse events. This trial is registered under the jRCT trial identifier:jRCTs031240046. Results: 64Cu-PD-32766 demonstrated good tolerability, with no serious complications observed. The average patient-level PET uptake positivity rate at 120 minutes was 75%. The average lesion-level PET positivity rate was 96.2%. Tumor uptake was highest at 60, 120 minutes post-administration. The effective dose for whole body was 0.102±0.036 mSv/MBq. The stomach and small intestine had the highest absorbed doses among all organs, with 0.712±0.287 mGy/MBq and 0.304±0.067 mGy/MBq, respectively. Conclusions: 64Cu-PD-32766 demonstrated an excellent positivity rate in ccRCC patients with no significant adverse events and tolerated radiation dose to normal organs, proving high diagnostic capability and suggesting future therapeutic uses by labeling with therapeutic radionuclides. Clinical trial information: jRCTs031240046 .
Treatment patterns in prostate cancer patients who received darolutamide in the ARAMIS trial in Spain: PARASEC study.
Authors: Javier Puente, José García Sánchez, Joan Folqué, Javier Casas
Journal: Journal of Clinical Oncology (2025)

142 Background: Darolutamide, enzalutamide or apalutamide have demonstrated to prolong overall survival in patients with non-metastatic castration-resistant prostate cancer (nmCRPC). Despite their effectiveness, almost all patients progress to mCRPC. In the last few years, several new options for treatment of advanced prostate cancer have shown survival benefit. Darolutamide showed significantly prolonged metastasis-free survival compared with placebo in patients with nmCRPC in ARAMIS phase III trial. There is a lack of data about treatment patterns of patients that progress after receiving darolutamide in nmCRPC in the real-world setting in this new scenario with so many treatments available. Methods: This is a retrospective, observational, multicenter, longitudinal follow-up study to describe the treatment patterns received by the Spanish patients who received darolutamide in the ARAMIS study, according to standard clinical practice in Spain. This study involved at Urology and Oncology Departments of 18 selected hospitals. Results: Eighty-five patients were included in the study; median age was 76 years; 49 patients (58%) progressed to mCRPC and, of these, 35 (71%) received treatment for mCRPC; median number of lines post-progression was 2 (range 1-5). Abiraterone (22/35 [63%]) and docetaxel (10/35 [29%]) were the most commonly used drugs in the first line, docetaxel (12/21 [57%]) and cabacitaxel (12/21 [19%]) in the second line and cabacitaxel (4/12 [33%]) and docetaxel (3/12/21 [25%]) in the third line. Eleven patients received palliative radiotherapy (11/35 [31%]) and 7 (7/35 [20%]) osteoclast targeted therapy (5 zoledronate and 2 denosumab) after darolutamide. Conclusions: The results show that 29% of patients who progressed to mCRPC do not receive treatment after darolutamide and of those receiving treatment, 63% receive abiraterone, which appears not to be in line with current European guidelines. Only one-fifth of patients receive osteoclast targeted therapy, which is clearly insufficient. The variability in the duration of treatments and sequences suggests a lack of consensus in Spanish clinical practice. It is critical to explore more standardized strategies to maximize treatment effectiveness in these patients.
Effectiveness and safety of RC48-ADC in combination with toripalimab as neoadjuvant treatment in HER2-positive muscular invasive urothelial bladder cancer patients.
Authors: Chenglong Li, Jiefu Zhu, Fan Cheng, Weimin Yu, Zhiyuan Chen, Chao Song, Hengcheng Zhu, Haoyong Li
Journal: Journal of Clinical Oncology (2025)

710 Background: Bladder cancer with high expression of human epidermal growth factor receptor 2 (HER2) is associated with pathological malignancy and poor prognosis. For patients with muscle-invasive bladder cancer that can be curative resected, the standard treatment is radical cystectomy and pelvic lymph node dissection following neoadjuvant chemotherapy (NAC). However, NAC is inefficient, and many patients cannot tolerate its adverse reactions. Therefore, a novel and safe strategy for these patients is needed after NAC. Methods: In this study, patients with muscle-invasive bladder cancer (MIBC) diagnosed with cT2a-4aN0M0 who were HER2 positive (HER2 IHC1+, 2+, or 3+) and intolerant to platinum underwent transurethral resection of bladder tumor (TURBT). This was followed by 4 cycles of toripalimab (200 mg, intravenous, D1, Q2W) combined with disitamab vedotin (2 mg/kg, intravenous, D1, Q2W) as neoadjuvant therapy. For patients who requested bladder preservation, we performed Re-cTURBT or multipoint biopsy to verify the status of residual tumors in the bladder. The primary endpoint was pathological complete response (pCR). Secondary endpoints included objective response rate (ORR), overall survival (OS), and safety. Results: A total of 28 patients were enrolled from April 2023 to Jun 2024 in our hospital. The median age was 68 years (range: 55-82). By the data cut-off in June 2024, 16 patients (57.1%) achieved clinical complete response (cCR). Among those who achieved cCR, the primary endpoint of pCR was 93.7% (15/16). The median follow-up time was 11.8 months. The median OS was not reached, ORR was 96.4% (27/28). Regarding safety, treatment-related adverse events (TRAEs) of any grade occurred in 21 patients (75%). The most common TRAEs were fatigue (68.3%), itching (57.5%), poor appetite (51.2%), alopecia (33.3%), and diarrhea (16.7%), all of which are grade 1-2. Grade 3 TRAE occurred in 4 patients (14.3%), with one patient experiencing cardiac tachycardia (3.5%) and 3 patients having hepatic dysfunction (10.7%). No grade 4 and 5 TRAEs were observed. Conclusions: Disitamab vedotin (RC48-ADC) combined with toripalimab as neoadjuvant treatment has shown excellent effectiveness and safety in curative resectable MIBC patients with HER2 positive. Those who achieved cCR and underwent Re-cTURBT and multipoint biopsy in bladder had an excellent pCR.
Development of a FKSI-23: A new bespoke health-related quality of life (HRQOL) questionnaire for the advanced and adjuvant setting in renal cell carcinoma (RCC).
Authors: Cristiane Decat Bergerot, Paulo Gustavo Bergerot, Daniela V. Castro, Benjamin Mercier, Elizabeth Nally, Adil Ali, Thomas E. Hutson, Axel Bex, Sarah P. Psutka, Brian I. Rini, Elizabeth R. Plimack, Viraj A. Master, Viktor Grünwald, Laurence Albiges, Toni K. Choueiri, Sumanta Kumar Pal, David Cella, Thomas Powles
Journal: Journal of Clinical Oncology (2025)

526 Background: Existing HRQOL measures may not fully capture the experiences of patients with localized and advanced RCC. This study aimed to develop a validated, patient-centered HRQOL metric by incorporating insights from patients, advocates, and clinical experts for both localized and advanced RCC. We previously developed a questionnaire for advanced RCC (Bergerot et al., JCO 2024). In this study, we integrate it into the FKSI-19 model and create a new questionnaire. Methods: A four-phase approach was used. Previous work in advanced RCC assessed item relevance from established HRQOL measures (FKSI-19, EORTC QLQ-C30, EQ-5D), refined through patient feedback and expert review. This phase expanded to include localized RCC in the adjuvant setting. In Phase 1, patients with localized RCC rated the the relevance of 54 items from the metastatic cohort. Phase 2 included a panel of 11 expert refining the adjuvant-specific items. Phase 3 gathered feedback from patient advocates, and Phase 4 further refined the items by harmonizing them with the FACT library for consistency across RCC stages. Results: In Phase 1, 6 of 54 items were rated as most relevant by patients with localized RCC. Phase 2 refined these further, excluding redundant items and adding 4 new questions focused on adjuvant therapy. Phase 3 led to minor revisions after advocate review, and Phase 4, the new items were harmonized with validated FACT library questions. The final adjuvant-specific questionnaire comprises 10 items, addressing concerns such as long-term side effects, surveillance anxiety, and post-surgery emotional distress. The advanced-specific version includes 13 items. Both versions deemed to be of utmost importance to patients with localized and advanced disease. These items can be used as standalone scoring options, resulting in the creation of a novel FKSI-23 metric, allowing for customized questionnaires tailored to specific clinical scenarios. Conclusions: Through collective input from patients, advocates and experts, novel items that aid in capturing the experience of RCC patients were identified and existing metrics were refined to generate separate “scoring options” for patients with localized and metastatic disease. Validation of the resulting FKSI-23 tool is underway in forthcoming studies in RCC.
Image-based artificial intelligence algorithms for molecular diagnostics in prostate pathology: How far are we? A systematic review.
Authors: Jacqueline E. van Hees, Michiel Vlaming, Nikolas Stathonikos, Britt B.M. Suelmann, Richard P. Meijer, Peter-Paul M. Willemse, Paul J. van Diest
Journal: Journal of Clinical Oncology (2025)

193 Background: Guidelines recommend molecular diagnostics for homologous and mismatch repair (MMR) defects in men with metastatic castration-resistant prostate cancer. However, in clinical practice, routine testing is hindered because it is costly, time-consuming and not available in all laboratories. Moreover, many patients need to be tested to identify the few with these genetic aberrations. To address these challenges, image-based artificial intelligence (AI) algorithms have been developed to predict molecular alterations from hematoxylin and eosin (HE) slides that are beyond the pathologist's visual detection. This review aims to assess the advancements of image-based AI algorithms in molecular diagnostics in prostate pathology and their potential in daily clinical practice. Methods: Through a search query, 3213 articles were identified and screened by two reviewers. In total, 12 articles were selected for this review and were assessed using the QUADAS-2 criteria. Results: Out of 12 articles, 5 focused exclusively on a specific set of preselected genes in prostate cancer, while the other articles examined broader ranges of genomic or transcriptomic changes, with some covering various cancer types. Training datasets consisted of up to 451 prostate cancer slides and most studies included only slides from radical prostatectomies. The majority made use of the cancer genome atlas program (TCGA). The best performance reported was 0.91 area under the curve (AUC) on internal and AUC of 0.89 on external validation. However, only 5 of the 12 studies performed external validation and none looked into the application of their algorithm in a clinical setting. Conclusions: Our review shows that in concept, AI is reasonably capable of detecting molecular changes based on HE slides of prostate pathology with reasonable predictive power. This has been shown in different specific genetic alterations, as well as in genome- or transcriptome-wide alterations. The predictive power of AI may however not be good enough to forgo molecular testing in patients predicted negative. Furthermore, these systems have only reached the developmental stage, leaving their potential performance in a clinical setting yet to be determined.
<sup>18</sup> F-PSMA-1007 PET/CT for response assessment in patients with metastatic renal cell carcinoma undergoing first line tyrosine kinase or checkpoint inhibitor therapy.
Authors: Michael D. Staehler, Sophie Kunte, Adrien Holzgreve, Marcus Unterrainer, Iulia Blajan, Christian G. Stief, Peter Bartenstein, Jozefina Casuscelli, Lena Unterrainer
Journal: Journal of Clinical Oncology (2025)

455 Background: Evaluating the effectiveness of systemic therapy in patients with metastatic renal cell carcinoma (mRCC) is crucial for timely treatment adjustments. In an earlier preliminary study on a subset of mRCC patients, we compared responses to systemic therapy using [¹⁸F]PSMA-1007 PET and conventional imaging methods. In this research, our aim was to compare response assessments using PSMA PET versus CT scans in a larger cohort of mRCC patients undergoing systemic therapy. Additionally, we investigated the potential of using PSMA-PET-derived responses to predict outcomes. Methods: We performed a retrospective single-center analysis of patients with mRCC who underwent [¹⁸F]PSMA-1007 PET/CT in the context of tyrosine kinase or checkpoint inhibition and had at least one PET avid metastatic RCC lesion at baseline. All patients were treated with IO combination therapy either in combination with a TKI or ICI. Early treatment response at a mean of 9.5 weeks after the start of systemic therapy was compared to baseline scans. PET responses and measurements were correlated with CT results, progression-free (PFS) and overall survival (OS). Survival data were analyzed using log rank testing and Kaplan-Meier analysis. Results: 25 patients with mRCC were enrolled. Median age was 65.2 years (range 24-87). Median PFS was 16.6 months (range 1.38 -58.69) and median OS 28.8 months (range 3.6 - 65.16). Median SUV, TTV, CT or PET response were not correlated with PFS or OS. Patients with a 10% reduction in SUVmax had a significant longer PFS with 23.1 months (95% CI 13.8-32.3) vs 3.6 (95% CI 1.4 – 5.9) months and OS of 36.2 months (95% CI 17.5 – 70.6) vs 11.1 months (95% CI 5.604 – 16.8) than patients without SUVmax response. SUVmax response was independent of administration of tyrosine kinase inhibitors or checkpoint inhibitors. Conclusions: Reduction of PSMA uptake on PET scans may be an independent biomarker beyond CT findings and warrants further investigation in mRCC. PSMA PET could be used for a better understanding of drug efficacy. Changes in PSMA PET are independent of the mechanism of action of systemic therapy in early prediction of therapy response and therefore might be considered a clinical biomarker.
Neoadjuvant treatment with disitamab vedotin plus perioperative toripalimab in patients with muscle-invasive bladder cancer (MIBC) with HER2 expression: Updated efficacy and safety results from the phase II RC48-C017 trial.
Authors: Xinan Sheng, Cuijian Zhang, Yongpeng Ji, Li Zhou, Benkui Zou, Hang Huang, Yonghua Wang, Kaiwei Yang, Xue Bai, Dan Feng, Yong Yang, Jiasheng Bian, Zhixian Yu, Haitao Niu, Peng Du, Jianmin Fang, Zhisong He, Jun Guo
Journal: Journal of Clinical Oncology (2025)

665 Background: This single-arm phase II trial was conducted to evaluate the efficacy and safety of neoadjuvent disitamab vedotin (DV, a HER2-targetted monoclonal antibody conjugated with monomethyl auristatin E) plus perioperative toripalimab (an anti-PD-1 inhibitor) in MIBC patients (pts) with HER2 expression. The preliminary results showed promising efficacy and acceptable safety with neoadjuvant treatment with DV plus toripalimab in pts with HER2-expressing MIBC (Sheng, et al. ASCO Annual meeting 2024). Methods: Key eligibility criteria included previously untreated MIBC (cT2-4aN0-1M0) with HER2 expression (immunohistochemistry [IHC] ≥1+ by local test), and eligible for curative-intent radical cystectomy and pelvic lymph node dissection (RC+PLND). Pts received DV (2 mg/kg) plus toripalimab (3 mg/kg) every 2 weeks for 6 cycles at neoadjuvant phase. After RC+PLND, pts received adjuvant toripalimab (3 mg/kg every 2 weeks) for up to 20 cycles. The primary endpoint was pathological complete response (pCR, ypT0N0) rate assessed by the investigators; secondary endpoints included pathological response rate (≤ypT1N0M0), overall survival, safety, etc. Here we present the updated efficacy and safety results and post-hoc event-free survival (EFS) analysis with data cutoff date (DCO) of September, 2024. Results: As of DCO, patient enrollment was completed with 47 pts enrolled and treated (including 10.6% pts with HER2 IHC 1+, 57.4% IHC 2+, and 31.9% IHC 3+; 83.0% pts at baseline T2-4N0M0 and 17.0% at cT2-4aN1M0 stage). RC+PLND was performed in 33 (70.2%) pts. The pCR rate was 63.6% (95% CI: 45.1%-79.6%) and the pathological response rate was 75.8% (95% CI: 57.7%-88.9%). A higher pCR rate of 84.6% was observed in patients with HER2 IHC 3+. The pCR rate was 77.8% and 62.5% in PD-L1-positive and PD-L1-negative subgroups, respectively. The one-year EFS rate was 89.5% (95% CI: 69.8%-96.7%). The safety profile was consistent with the previous ASCO presentation without new toxicity signals observed. No adverse events delayed the surgery. Survival data were immature. Conclusions: The updated data supported perioperative treatment with DV plus toripalimab had promising efficacy and acceptable safety in pts with HER2-expressing MIBC. It warrants further investigation in this patient population. Clinical trial information: NCT05297552 .