tbuckley/cabot-search huggingface dataset:
PD-1 inhibitor plus paclitaxel, pingyangmycin and platinum-based chemotherapy as bladder-sparing therapy for high-risk non-muscle-invasive bladder cancer/muscle-invasive bladder cancer: A retrospective study.
Authors: Jun Li, Ziyong Wang, Zheng Li, Ruiqian Li, Haiyang Jiang, Chen Hu, Ying Bi, Yong Zhu, Wenzhao Wu
Journal: Journal of Clinical Oncology (2024)

e16601 Background: Radical cystectomy (RC) in combination with cisplatin-based neoadjuvant chemotherapy is the standard approach for muscle-invasive bladder carcinoma (MIBC), and also a treatment option for high-risk non-muscle-invasive bladder cancer (HR-NMIBC), but removal of the bladder has a significant impact on pts quality of life. Bladder-sparing treatment have emerged to be an alternative choice for patients who are concerning about the life quality after surgery. we aim to investigate the efficacy and safety of neoadjuvant PD-1 inhibitor plus paclitaxel, pingyangmycin and platinum-based chemotherapy as a bladder-sparing therapy for high-risk NMIBC/MIBC patients. Methods: This retrospective study enrolled HR-NMIBC/MIBC patients who received at least one cycle of PD-1 inhibitor plus paclitaxel、pingyangmycin (bleomycin A5 hydrochloride) and platinum-based chemotherapy ["4P" therapy] and underwent imaging evaluation from Feb 2022 to Nov 2023. The objective response rate (ORR), pathological complete response rate (pCR), bladder-intact event-free survival (BI-EFS), Recurrence free survival (RFS), overall survive (OS) and adverse events (AEs) were observed. Results: Twenty-three pts (4 pts HR-NMIBC,19 pts MIBC) were included, with median age of 70 and 87.5% male, of which 5 pts (21.7%) received 1 cycle and 18 pts (78.2%) received 2 cycles of treatment. In all pts, the ORR was 87.0% (20/23), with 34.8% (8/23) had a complete response, 52.2% (12/23) had a partial response, 13.0% (3/23) had a stable disease. In different PD-1 therapy group, toripalimab group has 100% (15/15) of ORR, 40.0% (6/15) had a complete response; tislelizumab group has 62.5% (5/8) of ORR, 25.0% (2/8) had a complete response. 18 of the 23 pts underwent TURBT and 5 pts declined TURBT. Among 18 evaluable pts, pCR was achieved in 7 pts (38.9%). The cut-off date of data collection was Feb 1 2024, median follow-up time was 6.5 months[range:2.1-23.3 months], 2 patients relapsed and underwent TURBT without RC. None of the 23 patients have underwent RC. Survival data are not yet mature, 1 patient died of pneumonia (unrelated to chemotherapy or PD-1 inhibitor). Any grade of adverse event occurred in 23 pts (100%), grade 3 or higher toxicity rate was 30.4% (7/23). 18 pts (78.3%) experienced immune-related AEs, and 1 patient (4.3%) had grade 3 immune-related AEs. No discontinuations due to immune-related AEs. Conclusions: These data support neoadjuvant PD-1 inhibitor plus paclitaxel, pingyangmycin and platinum-based chemotherapy as a potential bladder-sparing option for patients with HR-NMIBC/MIBC.
Real-world (rw) treatment (tx) patterns, sequencing, and outcomes in US patients (pts) with locally advanced or metastatic urothelial cancer (la/mUC) treated with avelumab first-line maintenance (1LM).
Authors: Kenneth Robert Carson, Chiemeka Ike, Seyed Hamidreza Mahmoudpour, Sebastian Monzon, Stamatina Fragkogianni, Mairead Kearney
Journal: Journal of Clinical Oncology (2024)

e16621 Background: In June 2020, avelumab 1LM was approved in the US for pts with la/mUC without progressive disease (PD) after 1L platinum-based chemotherapy (PBC). This rw study describes pt characteristics, tx patterns, and outcomes in pts who received avelumab 1LM. We report exploratory analyses by baseline metastatic site. Methods: A retrospective cohort of pts diagnosed with la/mUC (T4b, N2/3, and/or M1) who received systemic tx after approval of avelumab 1LM was identified from deidentified records in the Tempus database. Pts with no evidence of PD after completing 1L PBC were considered eligible for 1LM. 1LM was differentiated from second-line (2L) tx based on recorded clinical intent or algorithmically based on immuno-oncology tx initiated within 180 days of 1L PBC completion without recorded PD. Rw overall survival (OS), progression-free survival (PFS), and time to next tx (TTNT) were estimated using Kaplan-Meier methods. Results: By data cutoff (Nov 2023), 1485 pts had received 1L tx after approval of avelumab 1LM. Median age at diagnosis was 70 y, 74% were men, 62% were White, 88% had transitional cell carcinoma, and 62% had metastatic/stage IV disease. 1L tx was PBC in 63% (942/1485), which included cisplatin in 62% (581/942), carboplatin in 34% (326/942), and oxaliplatin in 4% (35/942), alone or in combination. 87% (820/942) were eligible for 1LM after completing 1L PBC, of whom 38% (313/820) had recorded 1LM tx, which was avelumab in 58% (180/313). Median follow-up from 1LM start was 13.5 months. Median (95% CI) rwOS and rwPFS from avelumab 1LM start was 20.6 (17.6-25.3) and 6.2 (4.6-13.7) months, respectively. Analysis by metastatic site is shown in the table. After avelumab 1LM, 37% (67/180) received 2L tx, most commonly with enfortumab vedotin (EV; 64% [43/67]); median rwOS from start of 2L EV was 13.5 months (95% CI, 11.6-NE). Conclusions: Despite limited follow-up, this study demonstrates the rw effectiveness of avelumab 1LM in pts whose disease has not progressed on 1L PBC. Results corroborate JAVELIN Bladder 100 data and recent rw studies from multiple countries. Our study also provides early evidence of the use and effectiveness of 2L EV after the JAVELIN Bladder regimen of 1L PBC without PD followed by avelumab 1LM. Understanding OS outcomes in pts with specific metastatic patterns is important for improving individualized care. Future studies with longer follow-up are warranted to evaluate rw benefits of the avelumab 1LM in selected pt groups. [Table: see text]
Treatment patterns with intravesical bacillus Calmette-Guérin (BCG) in patients with non-muscle-invasive bladder cancer (NMIBC): A real-world data analysis.
Authors: Ran Sun, Bolan Linghu, Robert A. Somer, Shalaka Hampras, Sumeet Kaur Bhanvadia, Emily Scherer, Joel Greshock, Hussein Sweiti
Journal: Journal of Clinical Oncology (2024)

e16584 Background: Intravesical BCG is the recommended first-line treatment for high-risk NMIBC patients, with a recommended minimum 1-year duration consisting of 6 doses of induction followed by multiple doses of maintenance. However, up to approximately 50% of patients experience BCG failure, often within the first 6 months. Real world treatment patterns with BCG are not well understood. This study aims to characterize real-world BCG treatment patterns and treatment failure in NMIBC patients. Methods: This retrospective cohort study utilized comprehensive claims and electronic health record (EHR) from the US HealthVerity data between Oct 2015 and Dec 2022. This analysis included patients with NMIBC who received first BCG treatment within 90 days of their bladder cancer diagnosis, with a follow-up period of ≥ 3 years post BCG treatment. A descriptive analysis of the number of doses, treatment duration, and treatment discontinuation following the BCG initiation was conducted. Treatment discontinuation was defined as a gap of more than 1 year from the last BCG dose. Initiation of subsequent therapy post BCG was reported and used as a proxy for BCG failure. Results: A total of 13,525 patients met the study criteria and initiated BCG treatment between 2015 and 2022. Of all patients, 3193 (23.6%) received &lt; 5 BCG doses, 3854 (28.5%) received 5-7 doses, and 6478 (47.9%) received &gt; 7 BCG doses. The overall median was 7 doses (interquartile range [IQR]: 5,14). The median duration of BCG treatment was 156 days (IQR: 36, 489). BCG was discontinued in 66.9% patients within 1 year of initiation. A total of 6182 patients (45.7%) experienced treatment failure and received subsequent treatment, with 3550 patients (57.4%) initiating next treatment within 1 year of last BCG dose. Conclusions: In a large US real-world dataset, a majority of NMIBC patients treated with BCG received ≤7 doses and discontinued treatment within &lt; 1 year of treatment initiation. Furthermore, nearly half of patients experienced BCG failure, thereby requiring subsequent therapies. This highlights a significant unmet need for treatments with improved tolerability and efficacy profile for patients with NMIBC.
Real-world data (RWD) with avelumab in patients (pts) with locally advanced or metastatic urothelial cancer (la-mUC): The AVEBLADDER study.
Authors: Marta Sotelo, Mireia Pelaez, Laura Basterretxea, Estrella Varga, Ricardo Sánchez-Escribano, Eduardo Pujol, Carmen Santander, Mireia Martinez-Kareaga, Mikel Arruti Ibarbia, Inma Rodríguez Ledesma, Carlos Álvarez-Fernández, Pablo Piedra, Veronica Calderero, Nuria Lainez, Juan Antonio Verdun Aguilar, Irene Gil-Arnaiz, Ricardo Fernandez, Cristina Mazas, Ignacio Duran
Journal: Journal of Clinical Oncology (2024)

e16559 Background: Current standard of care for la-mUC pts who show no progression after platinum-based chemotherapy is maintenance with avelumab based on survival improvement (JAVELIN 100; Powles et al. NEJM 2020). However, the available RWD evidence on the use of avelumab in the E.U. is limited and there are concerns about the low uptake of this strategy based on figures from American series (Mamtani R et al; JAMA Netw Open 2023). We present here data on the use of avelumab in a large cohort of pts from different centres in Spain within the academic group GO NORTE. Methods: AVEBLADDER is a retrospective observational analysis in which clinical information was retrieved from pts treated across 14 centres in 13 provinces in Northern Spain. The study population included adult pts diagnosed with la/mUC (January 1, 2021-June 30, 2023) followed from date of diagnosis until death, loss to follow-up or end of study. Median overall survival (OS) was determined using the Kaplan-Meier method. Results: 419 pts were included. Median age was 71 [range 42-88]; 80% were males; 81% had primary bladder tumours and 94% predominant urothelial histology. Seventy three percent of pts had visceral/bony metastases and 59% were unfit for cisplatin. Most common 1 st line treatment (tx) [88%] was platinum-based chemotherapy [median number of cycles 4]. Out of 369 pts who received platinum-based chemotherapy, non-progression (CR, PR or SD) was reported in 230 pts [62%], of whom only 85 pts [37%] received maintenance avelumab. Fifty-eight pts treated with avelumab were evaluable for response: 7 (10 %) achieved a CR, 12 (14%) PR, 22 (26%) SD and 17 (20%) PD. The most common reason for non-receiving avelumab in our series was lack of access/reimbursement according to country/region policy. Overall, 168 pts [40%] started 2 nd line tx and atezolizumab was the most used agent, only 41 pts [24%] received third line tx. With a median follow-up of 11 months, 194 pts [46%] are still alive and median overall survival (OS) is estimated to be 28 months (95% CI 23-not reached) with maintenance avelumab vs 11 months (95% CI 9-13) for those who did not receive this drug. Conclusions: Despite the demonstrated improvement in OS for maintenance avelumab, its uptake in our series was low with roughly 40% of the pts. New policies and better access to the drug will most likely improve these figures and hopefully also the proportion of patients who progress to receive a third line where novel therapies are currently being implemented. AVEBLADDER is a study sponsored by GO NORTE a non-for-profit GU cooperative group.
Enfortumab vedotin plus pembrolizumab in the treatment of locally advanced or metastatic bladder cancer of variant histology: A phase II study.
Authors: Bassel Nazha, Jacqueline T Brown, Yuan Liu, Haydn Kissick, Bradley Curtis Carthon, Omer Kucuk, Lara R Harik, Vikram M Narayan, Shreyas S Joshi, Mehmet Asim Bilen
Journal: Journal of Clinical Oncology (2024)

TPS4615 Background: Bladder cancers of variant histology (BCVH) account for up to 25% of bladder cancer incidence and affected patients (pts) usually have poor outcomes. The treatment options are limited due to the underrepresentation or exclusion of BCVH pts from trials for locally advanced or metastatic urothelial cancer (mUC). Enfortumab vedotin (EV) is an antibody-drug conjugate specific for Nectin-4. In the EV 302 Phase III trial, EV+pembrolizumab (pembro) significantly prolonged overall survival (OS) compared to platinum-based chemotherapy in mUC (HR 0.47, 95% CI 0.38-0.58) and was recently FDA-approved as standard of care in 1L mUC. Translational studies from our center show Nectin-4 expression in many BCVH pts and data support immune-checkpoint inhibitor (ICI) activity in subsets of these pts. We hypothesize the presence of clinical activity of this combination in BCVH. Therefore, we designed this trial to assess the efficacy and safety of EV+pembro in locally advanced or metastatic BCVH (mBCVH). Methods: This is a Phase II, open-label, single-center trial at the Winship Cancer Institute of Emory University (NCT05756569) for pts with mBCVH. Pts will receive pembro 200mg IV on Day 1 and EV 1.25mg/Kg IV on Days 1 and 8 of a 21-day cycle for up to two years. The eligibility criteria include histologically confirmed variant histology or non-urothelial bladder cancer of epithelial origin including squamous cell carcinoma and adenocarcinoma (according to the WHO 2016 Classification), ECOG 0-1, and any line of therapy. Pts with neuroendocrine bladder cancer, non-epithelial cancers (e.g. sarcoma, lymphoma), prior ICI and/or EV treatment are excluded. Overall response rate (ORR) per RECIST 1.1 is the primary outcome and will be tested using Simon's two-stage design (n=25). The first interim analysis is planned after 15 patients. The desirable target is ORR≥30% relative to a null hypothesis of ORR ≤10%. This statistical design yields a type I error rate of 0.05 and a power of 80% for a true ORR≥30%. Key secondary outcomes include OS, progression-free survival, duration of response, and incidence of adverse events per CTCAE v5.0. Correlative biomarker analyses using blood- and tissue-based assays will be conducted during screening and at disease progression. The trial is currently open for enrollment. Clinical trial information: NCT05756569 .
Safety and immunological effects of ablative radiotherapy followed by pembrolizumab in patients with advanced adrenocortical carcinoma.
Authors: Nitya Prabhakar Raj, Christopher H. Crane, Etay Ziv, Anuradha Gopalan, Joanne F. Chou, Marinela Capanu, Diane Lauren Reidy, Carla Hajj
Journal: Journal of Clinical Oncology (2024)

TPS4630 Background: Adrenocortical carcinoma (ACC) is a rare and aggressive cancer with poor prognosis. While pembrolizumab is a NCCN recommended treatment, our prior study showed no benefit in patients with liver metastases (NCT02673333). 1 Preclinical evidence suggests combining liver-directed radiation therapy (RT) with pembrolizumab might enhance anti-tumor immunity. 2 Our current study will assess the safety and describe preliminary efficacy data for ablative RT to symptomatic liver metastases followed by treatment with pembrolizumab in patients with advanced ACC. Methods: This is a single-center pilot study. Main inclusion criteria include: adult patients with metastatic ACC with symptomatic liver metastases, presence of extrahepatic metastases, ECOG 0-1. Ablative RT in 5 or 10 once daily fractions will be delivered over 1 to 2 weeks; pembrolizumab treatment (200mg Q3W) will begin one week after RT completion. The primary objective is to evaluate the safety of treatment with ablative RT followed by pembrolizumab. The study will include a 6 patient safety lead-in, with 10 to 12 patients enrolled in total. The secondary endpoint, efficacy, is defined as the objective response (partial and complete response) according to RECIST v1.1, in the hepatic and extrahepatic disease. Correlative objectives include evaluation of the innate and adaptive immune response during treatment through analysis of pre- and on-treatment blood and tumor tissue samples, circulating tumor (ct) DNA analyses, and PD-L1 and next-generation sequencing testing in pre-treatment tumor tissue samples to evaluate for biomarkers of response and resistance. This trial began enrollment in 9/27/2023, with 3 patients enrolled to date. References: 1 Raj N, Zheng Y, Kelly V, Katz SS, Chou J, Do RKG, et al. PD-1 Blockade in Advanced Adrenocortical Carcinoma. J Clin Oncol. 2020;38(1):71-80. 2 Yu J, Green MD, Li S, Sun Y, Journey SN, Choi JE, et al. Liver metastasis restrains immunotherapy efficacy via macrophage-mediated T cell elimination. Nat Med. 2021;27(1):152-64. Clinical trial information: NCT06066333 .
PRadR: PSMA targeted radionuclide therapy in adult patients with metastatic clear cell renal cancer, a multicentric phase I/II.
Authors: Armelle Vinceneux, Anne-Sophie Bidaux, Claire Cropet, Delphine Tatu, Mathilde Bernardin, Séverine Neymarc, David Pérol, Jean-Pierre Pouget, Julie Constanzo, Nicolas Foray, Loic Djaileb, Antony Kelly, David Kryza, Anne-Laure Giraudet
Journal: Journal of Clinical Oncology (2024)

TPS4608 Background: Prostate Specific Membrane Antigen (PSMA) is highly expressed in neovessels of various solid tumors including Renal Cell Carcinoma, especially clear cell (ccRCC), which is the most frequent sub type. In ccRCC, PSMA expression in tumor vessels is correlated with higher grade and stage as well as in match between primary tumor and metastasis. PSMA may be a target expressed in metastatic ccRCC for radionuclide therapy using PSMA Ligands Radiolabeled with Lutetium-177 (PRLT), which is already used in daily practice for prostate cancer. 177 Lu-PSMA in prostate cancer with renal impairment appeared to be feasible and tolerable in previous studies. The aim of this Phase I/II study NCT06059014 is to assess the safety and clinical activity of this new Radiolabelled Therapy for mccRCC. Methods: PRadR is a multicentric, single-arm, open-label Phase I/II study evaluating PSMA targeted radionuclide therapy in adult patients with mccRCC. Patients must have received at least 2 prior regimens, including immunotherapy and antiangiogenic agents as per international guidelines, ECOG 0 to 1, with adequate hematologic, hepatic and renal function with a creatinine clearance according to CKD-EPI ≥ 40 mL/min/1.73m 2 . Only patients with tumor tracer uptake greater than background will be treated with 4 cycles of 7.4 GBq of 177 Lu-PSMA-1 every 6 weeks. The primary endpoints are the incidence of severe toxicity (Safety run in) and the disease control rate at 24 weeks (DCR-24W) as per RECIST V1.1 (Phase II) in patients with a PSMA-positive mccRCC selected through 68 Ga-PSMA PET. Secondary endpoints include overall response rate, duration of response, progression free survival, overall survival and safety according to NCI-CTCAE V5.0. During the safety run in, if more than one patient experiences severe toxicity during the first cycle over the first 6 treated patients, then a lower activity of 177 Lu-PSMA-1 will be evaluated in an additional cohort of 6 patients (5.9 GBq). Using a Fleming-A’Hern single stage design with a target DCR 24w of 30% and an inefficacy bound of 10% (α=5% one sided and 90% power) a total of 33 evaluable patients are required. If at least 7 successes (CR, PR or SD) at 24 weeks of treatment are observed, 177 Lu-PSMA-1 will deserve further investigation in this setting. Translational studies will consist in comparing efficacy and toxicity to dosimetry of 177Lu-PSMA-1 in normal tissues and tumor lesions, and biomarkers obtained from blood samples or tumor tissues. First patient was enrolled in November 2023. Clinical trial information: NCT06059014 .
Zanzalintinib (XL092) plus nivolumab in non-clear cell renal cell carcinoma: The randomized phase 3 STELLAR-304 study.
Authors: Sumanta Kumar Pal, Thomas Powles, Ravindran Kanesvaran, Mohan Liu, Zhong Wang, Aarohi Bhatt, Pritesh Patel, Cristina Suárez
Journal: Journal of Clinical Oncology (2024)

TPS4611 Background: Non-clear cell renal cell carcinoma (nccRCC) is a heterogenous group of rare, histologic subtypes with limited treatment options. There have been few dedicated randomized controlled studies in nccRCC, and novel treatment options supported by data from robust clinical trials are needed. Sunitinib, a tyrosine kinase inhibitor (TKI), is a commonly used therapy for nccRCC based on clinical benefit demonstrated in phase 2 trials. To date, no treatment has shown a significant overall survival (OS) improvement over sunitinib in any nccRCC subtype. Monotherapy with immune checkpoint inhibitors (ICIs) has shown only modest response rates, but TKI-ICI combinations have shown promising clinical activity in single-arm phase 2 trials. Zanzalintinib is a novel, multi-targeted TKI of VEGFR, MET, and the TAM kinases (TYRO3, AXL, MER) which are involved in tumor angiogenesis, metastasis, and immunosuppression. Zanzalintinib has shown antitumor and immunomodulatory activity in animal models when used alone or in combination with ICIs (Hsu et al. Mol Cancer Ther. 2023). In the phase 1 STELLAR-001 study, single-agent zanzalintinib showed promising antitumor activity (38% objective response rate [ORR] and 88% disease control rate) and a manageable safety profile in patients with heavily pretreated advanced clear-cell RCC (Pal et al. IKCS NA 2023. Abs 1). STELLAR-304 was designed to assess the efficacy and safety of zanzalintinib + nivolumab versus sunitinib in previously untreated advanced nccRCC. Methods: STELLAR-304 (NCT05678673) is a phase 3, global, randomized, open-label study enrolling patients ≥18 years of age with unresectable/advanced/metastatic nccRCC. Patients must have measurable disease per RECIST v1.1, a Karnofsky performance status of ≥70%, and papillary, unclassified, or translocation-associated histology (sarcomatoid features are allowed). Patients with chromophobe, renal medullary carcinoma, or pure collecting duct histology are excluded. Prior systemic anticancer therapy for advanced/metastatic nccRCC is not allowed; however, one prior systemic adjuvant therapy, including ICI (but excluding sunitinib), is permitted for completely resected RCC if recurrence occurred ≥6 months after the last adjuvant therapy dose. Patients (N=291) are randomized 2:1 to receive treatment with zanzalintinib + nivolumab, or sunitinib alone. The dual primary endpoints are progression-free survival and ORR per RECIST v1.1 by blinded independent radiology committee. The secondary endpoint is OS; safety will also be assessed. STELLAR-304 is currently recruiting patients in Europe, North and South America, and the Asia-Pacific region. Clinical trial information: NCT05678673 .