tbuckley/cabot-search huggingface dataset:
Treatment sequence (TS) and overall survival (OS) in patients with metastatic urothelial cancer (mUC): An observational, multicenter, real-life STATES-Bladder study.
Authors: Fabien Moinard-Butot, Jean-Baptiste Barbe-Richaud, Edwige Baudry, Karim Amrane, Denis Maillet, Philippe Barthelemy
Journal: Journal of Clinical Oncology (2025)

724 Background: mUC remains of poor prognosis despite standard first-line platinum-based chemotherapy (PBC), maintenance avelumab for ptd non progressing PBC. Enfortumab vedotin (EV) and erdafitinib offers a promising option in later lines of therapy. However all patients will not receive the whole sequence and the attrition rate remains crucial. As the therapeutic landscape evolved over the last 5 years no recent data are available on an whole mUC population including responder and non responder to PBC. This study aims to evaluate OS and treatment outcomes in real-world practice across multiple centers in France. Methods: This retrospective study included 180 patients with mUC treated with first-line PBC between January 2020 and December 2023. The primary objective was to assess OS in the overall population. Secondary objectives included OS by treatment sequence, performance status (PS), and attrition rates across treatment lines. We analyzed OS in patients receiving maintenance avelumab, those progressing to second-line therapies, and attrition at each treatment line. Additionally, OS was compared between patients with WHO PS 0-1 and WHO PS 2-3. Results: The median age was 72 years (41-91), with 81% male. Synchronous metastases were observed in 52% of patients, while 48% had metachronous metastases. The most common metastatic sites were lymph nodes (68%), lung (33%), bone (32%) and liver (21%). 44% of patients received cisplatin-based chemotherapy, while 56% were treated with carboplatin. Among patients with WHO PS 2-3 (20%), median age was 73 years (41-91), with a greater proportion having liver (25%) and bone (42%) metastases. For the entire population, median OS was 22.4 months [CI95%,17.2-26.7]. Patients receiving avelumab maintenance had a median OS of 29.0 months [CI95%,22.5-NA], while those progressing to second-line therapy showed a median OS of 15.6 months [CI95%,12.4-24.4]. Median OS for patients treated with EV at any treatment line was 26.1 months [CI95%,22.5-NA]. 58% of patients received avelumab maintenance. Attrition rates were 57% after first-line, 37% after second-line, and 9% after third-line therapy. Patients with WHO PS 0-1 had a significantly better median OS of 26.4 months [CI95%,22.5-NA], compared to 7.2 months [CI95%,6.1-13.1] for those with WHO PS 2-3 (p&lt;0.001). Conclusions: These real-world survival outcomes are consistent with large phase 3 trials. The particularly poor prognosis of patients with WHO PS 2-3 underscores the need for innovative treatment strategies, such as EV plus pembrolizumab, as highlighted by the EV-302 study, to potentially improve outcomes in this challenging subgroup.
A comprehensive evaluation of gene expression-based signatures for detecting tertiary lymphoid structures (TLS) in metastatic renal cell carcinoma (mRCC).
Authors: Eddy Saad, Nourhan El Ahmar, Berkay Simsek, Opeyemi Jegede, Sayed Matar, Razan Assaad Mohanna, Emre Yekeduz, David F. McDermott, Elizabeth R. Plimack, Jeffrey A. Sosman, Naomi Balzer Haas, Michael E. Hurwitz, Hans J. Hammers, Eliezer Mendel Van Allen, Toni K. Choueiri, Michael B. Atkins, Sabina Signoretti, David A. Braun
Journal: Journal of Clinical Oncology (2025)

591 Background: TLS are organized lymphoid aggregates linked to improved response to immunotherapy in multiple cancers, including mRCC. Traditionally, TLS assessment relies on pathological staining of tumor sections. In this study, we evaluated the performance of TLS gene-expression signatures as an alternative diagnostic tool. Methods: Primary tumors from treatment-naïve patients with mRCC in the HCRN GU16-260 trial were analyzed using multiparametric immunofluorescence (IF), staining for CD3, CD20 (TLS), CD21 (mature TLS), and CD8. The counts and densities of total and mature TLS were calculated. Bulk RNA sequencing was performed on the same specimens, and 4 gene signature scores (Meylan, Cabrita, Coppola, and Ng) were estimated using gene set variation analysis (GSVA). Spearman's correlations between signature scores and TLS IF parameters, as well as the area under the receiver operator characteristic (AUROC) curve, were computed. Results: Our cohort included 78 patients with matched IF and RNA-seq data. All 4 TLS signatures demonstrated strong predictive performance for detecting the presence (vs. absence) of TLS by IF in each sample (AUROC 0.8 to 0.85). Quantitatively, the 4 TLS signature scores, measured as continuous variables, correlated with IF-based counts and densities of total TLS, and to a lesser extent, mature TLS (Table). In terms of comparative performance, Meylan’s signature showed the highest correlation with IF TLS features, while Ng’s was the least correlated (Table). Furthermore, Meylan’s signature achieved the best predictive ability to stratify high vs. low TLS (AUROC 0.83) and was more specifically correlated with TLS compared to CD8 density (Table). Conclusions: Expression-based signatures exhibit robust predictive ability for TLS detection and quantification, similar to previously established CD8 signatures, and represent valid surrogate tools to complement pathological diagnosis. Spearman’s correlations between IF parameters and TLS signatures. Parameter Meylan Cabrita Coppola Ng Total TLS count ρ=0.65, P= 1.1x10 -10 ρ=0.58, P= 2.9x10 -8 ρ=0.56, P= 7.1x10 -8 ρ=0.42, P= 1.4x10 -4 Mature TLS count ρ=0.51, P= 2.1x10 -6 ρ=0.41, P= 1.8x10 -4 ρ=0.34, P= 2.3x10 -3 ρ=0.39, P= 5.0x10 -4 Total TLS density ρ=0.63, P= 6.1x10 -10 ρ=0.58, P= 3.4x10 -8 ρ=0.55, P= 2.2x10 -7 ρ=0.42, P= 1.4x10 -4 Mature TLS density ρ=0.49, P= 5.1x10 -6 ρ=0.39, P= 3.5x10 -3 ρ=0.32, P= 4.3x10 -3 ρ=0.38, P= 6.8x10 -4 CD8 density ρ=0.42, P= 3.1x10 -4 ρ=0.62, P= 2.1x10 -8 ρ=0.67, P &lt;2.2x10 -16 ρ=0.35, P= 2.9x10 -3
Efficacy and safety of lenvatinib plus everolimus in metastatic renal cell carcinoma after immune checkpoint and VEGFR tyrosine kinase inhibitors.
Authors: So Heun Lee, Inkeun Park, Shinkyo Yoon, Jae Lyun Lee
Journal: Journal of Clinical Oncology (2025)

489 Background: Limited studies have investigated the real-world effectiveness and safety of Lenvatinib (LEN) combined with everolimus (EVE) in metastatic renal cell carcinoma (mRCC), particularly after failure of immune checkpoint inhibitors (ICIs) and VEGFR tyrosine kinase inhibitors (TKIs). This study aimed to evaluate the efficacy and safety of LEN plus EVE in patients who had progressed after these prior therapies. Methods: This single-center retrospective study included mRCC patients at Asan Medical Center, Korea, who initiated LEN plus EVE as second-line or later therapy between September 2017 and June 2024. We reviewed electronic medical records for dosage, dose reductions, discontinuation, response, progression, and survival outcomes. The primary objectives were objective response rate (ORR) and progression-free survival (PFS), with secondary objectives including overall survival (OS), adverse events, and prognostic factors. Results: Eighty-two eligible patients were included, predominantly with clear cell type (n=74, 90.2%). ECOG performance status was 1 in 54 patients, and 2 in 26. At treatment initiation, the IMDC risk distribution was favorable (n=6, 7.3%), intermediate (n=48, 58.5%), and poor (n=28, 34.1%). The median number of prior therapies was four (range, 1-7), with 80.5% receiving LEN plus EVE as fourth-line or later therapy. All patients had prior anti-angiogenic TKI exposure, 86.6% had been treated with ICIs, and 37.8% had prior mTOR inhibitor therapy. The ORR was 39.0% (n=32/82), with a disease control rate (DCR) of 81.7% (n=67/82). The median follow-up duration was 21.8 months. The median time to progression (TTP) was 6.4 months (95% Confidence Interval [CI], 5.4-9.7), while the median PFS was 5.4 months (95% CI, 4.3-6.4), and the median OS was 7.7 months (95% CI, 6.2-12.1). Subgroup analyses indicated comparable ORR and PFS for patients treated beyond the fourth line (ORR 36.4%, PFS 5.3 months), those previously exposed to mTOR inhibitors (ORR 29.0%, PFS 5.5 months), and those who had progressed after both ICI and TKIs (ORR 38.0%, PFS 5.3 months). The median treatment duration was 6.8 months. Adverse events were significant: 54.9% required dose reductions of LEN, and 25.6% experienced treatment interruptions. For EVE, 17.1% required dose reductions, and 25.6% had interruptions due to toxicities. Notably, 31 patients (37.8%) developed proteinuria, with 18 experiencing grade 3 or higher. Conclusions: LEN plus EVE shows promising efficacy and disease control in heavily pretreated mRCC patients after failure of ICIs and VEGFR TKIs, even beyond the fourth line and in those previously treated with mTOR inhibitors. The safety profile aligns with known adverse effects, but the high incidence of proteinuria is notable. Further studies are warranted to optimize treatment protocols in this patient population.
Fifteen-year outcomes of external radiation with or without 6 months of neoadjuvant deprivation therapy for intermediate risk prostate cancer.
Authors: Barry Goy, Janis Yao
Journal: Journal of Clinical Oncology (2025)

388 Background: Our aim is to retrospectively compare survival outcomes in intermediate-risk prostate cancer (IRPC) treated with external-beam radiation therapy (EBRT) with or without neoadjuvant-deprivation-therapy (NADT). Methods: Retrospective analysis was performed on 566 IRPC treated with EBRT from 2004-2007. NADT was given to 336 patients, while 230 underwent EBRT alone. Median duration of NADT was 6 months. Median dose of radiation was 75.6 Gy to isocenter. Freedom-from-biochemical-failure (FFBF) was defined by the PSA nadir+2.0. Multi-variable analysis and Kaplan-Meier estimates were performed. Results: Median follow-up was 11.5 years in the NADT+EBRT vs 12.0 years in the EBRT alone group, with up to 19.8 years of follow-up. NADT+EBRT had more adverse factors of clinical stage (p=0.02), iPSA (p&lt;0.01), Gleason group (p=0.02), %cores&gt;50% (p&lt;0.01). 15-year FFBF, metastases-free-survival (MFS), prostate-cancer-specific-survival (PCSS), and overall survival (OS) for NADT+EBRT vs EBRT alone was 52% vs 49% (p=0.41), 85% vs 83% (p=0.59), 91% vs 91% (p=0.67), 53% vs 51% (p=0.82). Conclusions: After 15 years of follow-up, IRPC treated with EBRT with or without 6 months of NADT experienced a high PCSS of 91%, despite a very high PSA failure rate of about 49-52% of the patients. It’s unclear if 6 months NADT in addition to EBRT can improve PCSS or overall survival for IRPC, or just merely delay PSA progression.
A phase I first-in-human clinical trial with PLZ4-coated paclitaxel-loaded micelles (PPM) in therapy-resistant non-muscle-invasive bladder cancer (NMIBC).
Authors: Chong-xian Pan, Juan Garisto, Lori Lerner, Matthew Mossanen, Marc Dall'era, Hizra Farrukh, Colleen Hynes, Mamta Parikh, Primo N Lara, Urvashi Bhardwaj, Ai-Hong Ma, Joyce S. Lee, Yuanpei Li, Tzu-yin Lin, Yanxiao Jiao, Junwei Zhao, Ruiwu Liu, Kit S Lam
Journal: Journal of Clinical Oncology (2025)

806 Background: Approximately 75% of patients with non-muscle invasive bladder cancer (NMIBC) treated with transurethral resection (TUR) followed by intravesical Bacillus Calmette-Guérin (BCG) experience cancer recurrence. When BCG-unresponsive, most patients continue to have recurrences even with newly approved therapies and nearly 30% progress to invasive stages. We developed a first-in-class bladder cancer-specific nanotherapeutic, PPM, which is administered intravesically. Our preclinical data has demonstrated PPM can selectively target bladder cancer cells and deliver paclitaxel payload into these cancer cells following intravesical or intravenous administration. Methods: This is a 3+3 first-in-human dose escalation trial. Eligible patients must have pathologically confirmed NMIBC, be unresponsive to intravesical BCG therapy (with or without cytotoxic chemotherapy), possess adequate vital organ function, and consent to cystoscopy with TUR for response evaluation. PPM is administered via intravesical instillation once weekly for six weeks. The trial features three dose levels, with paclitaxel doses of 25 mg, 50 mg, and 75 mg. The primary endpoints include safety and the recommended Phase II dose; secondary endpoints encompass response rate, duration of response, systemic drug absorption, and molecular correlative studies. Patients will be followed at 3 month intervals for 2 years or until disease progression. Results: To date, three patients with pathologically confirmed NMIBC have completed a total of 18 treatments at the first dose level without any PPM-related adverse events: one patient was unresponsive to BCG and intravesical mitomycin therapy, while the other two had BCG-unresponsive disease. Two out of the three patients achieved ongoing complete remission for over six and nine months, respectively. The third patient demonstrated persistent disease, but no progression was noted. Enrollment for Dose Level 2 is currently open. Conclusions: PPM has demonstrated promising clinical activity without toxicity at the first dose level in patients with BCG-unresponsive NMIBC. Data at other dose levels will be presented at the meeting (ClinicalTrials.gov identifier: NCT05519241). Clinical trial information: NCT05519241 .
Racial differences in active surveillance intensity and overtreatment in men with prostate cancer.
Authors: Dawson Hill, Samuel R Kaufman, Paula Guro, Sarah Leick, Preeti Chachlani, Addison Shay, Mary Oerline, Christopher Dall, Brent K. Hollenbeck, Vahakn B Shahinian, Arnav Srivastava
Journal: Journal of Clinical Oncology (2025)

316 Background: Marginalized communities in cancer care are often characterized by lower healthcare utilization. In prostate cancer, however, utilization may have mixed effects on quality, particularly in the Medicare population where non-cancer health risks are more prevalent. In this context, we examined racial differences in active surveillance intensity (i.e. confirmatory testing) and potential overtreatment, two key measures of prostate cancer care quality. Methods: Using a 20% national sample of Traditional Medicare beneficiaries, we identified men with newly diagnosed prostate cancer from 2014 to 2019. We used multivariable logistic regression to evaluate the association between race (White, Black, or other) and receipt of a confirmatory test (prostate biopsy, magnetic resonance imaging, or genomic testing) within one year of diagnosis among men on active surveillance. We created a subset of patients with significant comorbidities to assess potential overtreatment (i.e., treatment among patients with &gt;50% estimated non-cancer mortality in five years). Results: We identified 41,092 men meeting inclusion criteria. On adjusted analysis, Black men (OR=0.75; 95%CI: 0.62-0.92, p=0.01) had lower odds of receiving a confirmatory test compared to White men. Among men at risk of overtreatment, Black men (OR=0.86; 95%CI: 0.77-0.97, p=0.01) were less likely to receive treatment compared to White men. Further, all patients, regardless of race, had a predicted probability &lt;50% of receiving a confirmatory test within one year of diagnosis (Table). Conclusions: Our study highlights racial differences in two measures of prostate cancer care, receipt of a confirmatory test and overtreatment. We demonstrated that Black men have lower odds of receiving a confirmatory test. This stands to disproportionately affect Black men, given that they present with higher risk tumors compared to other racial groups. Conversely, Black men have lower odds of being overtreated when compared with White men, suggesting that lower utilization may shield them from potential overtreatment and its related morbidity. As a result, policy efforts aiming to reduce disparities may be most impactful by prioritizing clinical contexts where utilization and access are tightly aligned with care quality. Predicted probabilities for confirmatory testing and overtreatment. White Black Other Confirmatory Testing 43% 37%* 46% Overtreatment 50% 43%* 46%* Adjusted for socioeconomic status tertile, Charlson Comorbidity Index, age, rurality, and year of diagnosis. *Indicates p&lt;0.05.
Real-world analysis of the efficacy and safety of enfortumab vedotin in patients with locally advanced or metastatic urothelial carcinoma: A multicenter retrospective study.
Authors: Shingo Hatakeyama, Kai Ozaki, Hayato Yamamoto, Yuya Sekine, Kanami Mori, Mizuki Kobayashi, Kazuyuki Numakura, Takahiro Yoneyama, Satoshi Sato, Tomonori Habuchi, Chikara Ohyama
Journal: Journal of Clinical Oncology (2025)

712 Background: We investigated the efficacy and safety enfortumab vedotin (EV) in patients with locally advanced or metastatic urothelial carcinoma in real-world practice. Methods: This multicenter retrospective study included 419 patients treated for locally advanced or metastatic urothelial carcinoma between April 2004 to April 2024. The patients were categorized into the following three groups: 87 patients who underwent first-line chemotherapy and sequential chemotherapy alone (chemo-alone group), 217 patients who underwent maintenance immunotherapy or second-line immunotherapy after first-line chemotherapy (chemo-ICI group) and 115 patients who were treated with EV after first-line chemotherapy and immunotherapy (chemo-ICI-EV group). The primary outcome was the comparison of progression-free survival (PFS) of first-line therapy and overall survival (OS) from first-line therapy between the three treatment groups. Secondary outcomes included the efficacy and safety in the chemo-ICI-EV group focusing on skin adverse events (AEs). Results: The OS from first-line therapy was significantly longer in the chemo-ICI-EV group than that in the other groups. There was no significant difference in the first-line PFS of first-line therapy between the three groups. A multivariable Cox regression analysis showed the administration of EV was significantly associated with prolonged OS. Skin AEs were observed in 69 (60%) as a major adverse event. The PFS and OS in the patients with skin AEs was significantly longer than in the patients without skin AEs despite the reduced dose of EV. A multivariable Cox regression analysis showed that skin AEs were significantly associated with prolonged RFS and OS. Conclusions: The administration of EV significantly improved oncological outcomes in the real-world practice. Dose adjustment of EV may be key for long-term use and oncological outcomes.
Systemic therapies in renal cell carcinoma with brain metastases: A comparative meta-analysis of immunotherapy and tyrosine kinase inhibitors.
Authors: Abdur Jamil, Zaheer Qureshi, Roshmita Bardhan, Mohsin Ahmad, Insija Ilyas Selene
Journal: Journal of Clinical Oncology (2025)

559 Background: Renal cell carcinoma (RCC) with brain metastases presents a clinical challenge. Management remains unclear, as systemic therapy data are limited and many trials exclude patients with active brain metastases. Current treatment primarily involves CNS-targeted radiation (e.g., stereotactic radiosurgery and whole-brain radiation therapy), while systemic therapies like tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs) are underexplored. This meta-analysis evaluates the efficacy of systemic treatments and whether these patients should continue to be excluded from clinical trials. Methods: A systematic search of PubMed, CENTRAL, MEDLINE, and Google Scholar was conducted through October 2024, focusing on studies of mRCC patients with brain metastases treated with ICIs, TKIs, or their combination. ICI therapies included nivolumab, ipilimumab, pembrolizumab, atezolizumab, and avelumab, while TKIs included sorafenib, sunitinib, and cabozantinib. Case reports, ongoing trials, narrative reviews, and meta-analyses were excluded. Primary endpoints were complete response (CR), partial response (PR), objective response rate (ORR), and overall survival (OS). Statistical analyses used fixed/random-effects models based on heterogeneity. Results: Nineteen studies involving 947 mRCC patients with brain metastases were included. The pooled analysis showed an ORR for ICIs of 29.9%, with a CR of 3.4% and PR of 28.9%. Brain-specific ORR, CR, and PR for ICIs were 27.5%, 10.8%, and 17.9%. TKIs alone showed a pooled ORR of 11.7%, with a CR of 1.3% and PR of 11.6%. Brain-specific ORR, CR, and PR for TKIs alone were 38.1%, 6.9%, and 29.5%. Only one study reported on ICI-TKI combinations, with an ORR of 0%. Survival analysis showed significantly worse OS for brain metastasis patients treated with ICIs plus TKIs (HR: 2.06, p=0.001) and TKIs alone (HR: 2.51, p=0.02) compared to those without brain metastases. Conclusions: ICIs had superior overall response rates compared to TKIs and ICI-TKI combinations in mRCC patients with brain metastases. Brain-specific response rates were similar between ICIs and TKIs. Given the poor prognosis of brain metastasis patients treated with TKIs, further research is needed to determine if they should continue to be excluded from trials. Larger prospective studies are required to confirm these findings and optimize treatment.
Circulating tumor DNA levels and related kinetics as prognostic biomarkers for clinical outcomes in mCRPC: A post hoc analysis of CM 7DX.
Authors: Karim Fizazi, Fred Saad, Teresa Alonso Gordoa, Philippe Barthelemy, Jeffrey C. Goh, Tomáš Büchler, Daniel Castellano, Chung-Wei Lee, Ding Jiang, Pradipta Ray, David Paulucci, Ana Lako, Saurabh Gupta, Aranzazu Campos, Sumit Kumar Subudhi, Maximiliano A.G. Van Kooten Losio, Hernán Javier Cutuli
Journal: Journal of Clinical Oncology (2025)

252 Background: Liquid biopsy assays in mCRPC are utilized for treatment eligibility of PARP inhibitors (HRR) and Pembrolizumab (MSI High). These ctDNA targeted gene panels provide translational data beyond gene mutations. Tumor Fraction (TF), the percentage of cfDNA from tumor, is a promising prognostic efficacy biomarker in pre-chemo mCRPC, and a potential predictive biomarker to post-chemo PSMA radioligand therapy. Methods: We analyzed ctDNA run with Illumina-TSO500 from the CA209-7DX Ph3 mCRPC trial (Nivo+chemo vs. Chemo in chemo-naïve mCRPC) to determine: TF at baseline or changes at Cycle6 Day1 (C6D1). TF at each timepoint was determined through the maximum somatic allelic frequency. Results: We present a combined analysis of treatment arms as both showed similar association between clinical outcomes and TF levels as well as clearance. Out of 1030 ITT patients TF data was available for 527 (51%) patients. Patients in the highest TF tertile had TF of ≥4.6% and TF&lt;0.3% for the lowest tertile. Patients in the lowest TF tertile had 10 months longer overall survival (OS) to the highest TF tertile (p&lt;0.001). Patients in the highest TF tertile demonstrated higher hazard ratio for OS (HR 3.42,[2.34-4.98] p&lt;0.001) and rPFS (HR 1.95 [1.47-2.59], p&lt;0001) over lowest tertile. This differential was maintained across arms and indicates that TF is a strong prognostic biomarker. High TF outperformed common stratification factors (prior exposure to chemo in CSPC or novel ARPIs) for poor prognostication in a multivariate analysis. TF high patients have higher rates of AR-Amp/AR-LBD mutations (72.6%) than TF low (28.8%). Patients with TF clearance, defined as TF &lt; 1% at C6D1 had 8 months mOS advantage over patients with a TF &gt;1% at baseline and on-treatment. TF clearance strongly correlated with OS (HR=0.42 [0.28-0.62], p&lt;0.001), rPFS benefit (HR=0.24 [0.17-0.34], p&lt;0.001) and PSA response (28% vs. 62%) regardless of treatment arm. Conclusions: This data advocates for plasma TF as a robust prognostic biomarker and as a potential stratification opportunity in mCRPC clinical trials. TF clearance may act as an early indicator of treatment response and hence can be an important monitoring tool for mCRPC patient management. Clinical trial information: NCT04100018 .