tbuckley/cabot-search huggingface dataset:
Stratified absolute benefit with adjuvant immunotherapy (aIO) in muscle-invasive bladder cancer (MIBC): A meta-analysis.
Authors: Syed Arsalan Ahmed Naqvi, Akshat Saxena, Kunwer Sufyan Faisal, Arifa Bibi, Muhammad Ali Khan, Ewan Kemar Cobran, Syed A. Hussain, Irbaz Bin Riaz, Alan Haruo Bryce, Parminder Singh
Journal: Journal of Clinical Oncology (2024)

e16619 Background: Should patients (pts) with MIBC receive aIO given the DFS benefit seen in AMBASSADOR and CheckMate 274 trials is an important clinical question. Thus, we aimed to quantify the magnitude of absolute benefit across different subgroups to aid clinicians in shared decision-making with their patients. Methods: Phase III trials evaluating aIO as compared to observation or placebo (obs/plac) in pts with MIBC were considered eligible. Outcomes of interest included DFS and OS. Pre-specified subgroups included disease location, PDL1 status, neoadjuvant chemotherapy (NAC) receipt, and tumor and nodal (TN) staging. Pairwise comparisons were made using a DerSimonian-Lairds (DL) random-effects meta-analysis. Stratified baseline risks (obtained from clinical trials) and relative effect estimates were used to estimate corresponding intervention risks (CIRs). The difference in CIRs and baseline risk was calculated to present absolute risk differences (ARDs) in each subgroup category. Results: Analysis included three trials with 2220 pts (pembrolizumab, nivolumab, and atezolizumab assessed in each). No significant difference was observed in OS with aIO compared to obs/plac (hazard ratio: 0.91; 0.76-1.09). However, aIO significantly improved DFS compared to obs/plac (0.76; 0.64-0.91) in the overall population. In pts with bladder/lower tract disease, aIO improved DFS compared to obs/plac (0.72; 0.56-0.92); however, no significant difference was observed in DFS in pts with upper tract disease. There was a statistically significant effect modification by disease location (p: 0.01). Adjuvant IO significantly improved DFS in PDL1- (0.78; 0.64-0.94) but not in PDL1+ pts (0.75; 0.52-1.08). Likewise, aIO significantly improved DFS in pts who received NAC (0.69; 0.53-0.90) but not in pts who did not receive NAC (0.89; 0.75-1.05). In terms of TN staging, aIO improved DFS in T2-3N0 (0.73; 0.57-0.94), T4N0 (0.76; 0.61-0.95), and in T2-4N1 patients (0.75; 0.59-0.95). No statistically significant modifications were observed among these subgroups. Stratified ARDs for DFS by each subgroup are outlined (Table). Conclusions: When delayed disease progression is a vital consideration, a risk-adapted strategy for the optimal patient selection to receive aIO should be considered. Disease location (lower tract/bladder), node positivity, and receipt of NAC emerged as groups likely to derive greater benefit with aIO. [Table: see text]
Clinical characteristics of renal cell carcinoma in the transplanted kidney in renal transplant recipients: A systematic scoping review.
Authors: Manasawee Tanariyakul, Sakditad Saowapa, Noppawit Aiumtrakul, Onsinee Wittanakorn, Chalothorn Wannaphut, Natchaya Polpichai, Pitchaporn Yingchoncharoen, Jared David Acoba
Journal: Journal of Clinical Oncology (2024)

e16518 Background: Renal transplant recipients are at a 100-fold increased risk of developing renal cell carcinoma (RCC), with a higher incidence of RCC in native kidneys than in allografts. Given that kidney transplant recipients typically possess only one functional kidney, it is critical for clinicians to heightened disease awareness. This systematic scoping review aims to provide an updated overview of the clinical characteristics, treatment, and outcomes of RCC in the allograft kidneys. Methods: We comprehensively searched the databases of MEDLINE and EMBASE until January 2024. Included studies were case reports, case series and retrospective analyses reporting RCC in the allograft kidney of renal transplant recipients. The review delineates the clinical presentation, time between kidney transplant and diagnosis, donor characteristic, mass size, histopathology and treatment outcome of RCC in the allograft kidneys. Results: Forty-two case reports and case series, along with eleven retrospective cohorts were found. 65 patients were identified in the case reports and case series, while 209 patients were reported in the retrospective study reviews. The review emphasizes that 75.4% of patients with allograft RCC were asymptomatic at the time of diagnosis, with the majority diagnosed through imaging surveillance. Symptomatic patients most commonly presented with gross or microscopic hematuria, elevated creatinine, abdominal or graft pain, respectively. 61.9% of recipients received their allograft from deceased donors, and 38.1% from living donors. The average time interval between kidney transplantation and the diagnosis of RCC spans 11.6 years, ranging from 6 months to 30 years. Papillary RCC and clear cell RCC (ccRCC) were the two most common histopathological diagnoses, with papillary RCC accounting for 53.3% and ccRCC for 34.2% of cases. A potential limitation is the inconsistent of long-term follow-up data for most of the subjects, which makes the outcome of this population uncertain. Conclusions: This systematic scoping review identified an average time interval of 11.6 years between kidney transplantation and RCC diagnosis, with a range from 6 months to 30 years. The majority of kidney transplant recipients with allograft RCC (75.4%) were asymptomatic, while the remainder presented with symptoms such as hematuria, elevated creatinine, abdominal or graft pain, weight loss, fever, malaise, or hypertension. The incidence of asymptomatic allograft RCC among kidney transplant recipients underscores the importance of vigilant post-transplant screening. Future research should investigate clinical outcomes and the cost-effectiveness of the screening practices in allograft kidney to develop preventive strategies.
Circulating kidney injury molecule-1 (KIM-1) biomarker analysis in IMmotion010: A randomized phase 3 study of adjuvant (adj) atezolizumab (atezo) vs placebo (pbo) in patients (pts) with renal cell carcinoma (RCC) at increased risk of recurrence after resection.
Authors: Laurence Albiges, Axel Bex, Cristina Suárez, Robert Uzzo, Xiaobin Tang, Zoe June Assaf, Sarita Dubey, Erik T. Goluboff, Corey Carter, Romain Banchereau, Mahrukh A Huseni, Sumanta Kumar Pal, Brian I. Rini
Journal: Journal of Clinical Oncology (2024)

4506 Background: In IMmotion010, adj atezo did not prolong investigator-assessed disease-free survival (DFS; primary endpoint) vs pbo after resection in pts with RCC (HR: 0.93, 95% CI: 0.75, 1.15; P=0.50; Pal Lancet 2023). This exploratory analysis of circulating protein biomarkers was performed to identify high-risk pts with minimal residual disease (MRD) who may show differential benefit from treatment (tx) with atezo. Methods: Pts with RCC with clear-cell or sarcomatoid component and increased recurrence risk post nephrectomy were randomized 1:1 to atezo 1200 mg or pbo IV q3w for 16 cycles or 1 year. A retrospective proteomics analysis was done with an affinity-based proximity extension assay (PEA) panel of ≈3000 analytes to identify circulating proteins with differential abundance patterns in matched serum samples (baseline vs at recurrence). A high sensitivity electrochemiluminescence (ECL) assay was then used to evaluate levels of KIM-1, a membrane glycoprotein overexpressed in clear-cell and papillary RCC, in all available baseline and post-tx serum samples. Outcomes in pts with KIM-1 high (≥86 pg/mL) vs low status at baseline were analyzed. Results: In pts with matched PEA samples (n=73), circulating KIM-1 was identified as the most significantly enriched protein at recurrence vs baseline. Of 778 pts enrolled in IMmotion010, 752 (97%) had baseline KIM-1 data (high: 300 [40%]; low: 452 [60%]). KIM-1–high status was associated with reduced DFS, and pts with KIM-1 high had better DFS with atezo vs pbo (Table). Longitudinal analysis of matched samples showed that in KIM-1–high pts, 9% (12/138) and 26% (36/141) of pts had a ≥30% increase from baseline in KIM-1 levels at Cycle 4 Day 1 with atezo vs pbo, compared with 16% (34/213) and 12% (25/207) in KIM-1-low pts, respectively. A ≥30% KIM-1 increase was associated with worse DFS in both KIM-1–high (atezo HR: 1.68, 95% CI: 0.77, 3.69; pbo HR: 3.53, 95% CI: 2.24, 5.58) and KIM-1–low (atezo HR: 3.56, 95% CI 2.21, 5.75; pbo HR: 3.22, 95% CI: 1.81, 5.70) subgroups. In pts with matched ECL samples (n=103), median KIM-1 levels were higher ( P&lt;0.001) at recurrence (172 pg/mL) than at baseline (79 pg/mL). Conclusions: In IMmotion010, high baseline serum KIM-1 levels were associated with poorer prognosis but improved clinical outcomes with atezo vs pbo. Increased post-tx KIM-1 was associated with worse DFS. These data suggest that circulating KIM-1 may be a non-invasive marker of MRD and disease recurrence and be associated with benefit from atezo in adj RCC. Further investigation of KIM-1 in adj RCC is warranted. Clinical trial information: NCT03024996 . [Table: see text]
Real-world outcomes among patients with advanced/metastatic renal cell carcinoma (mRCC) treated with tyrosine kinase inhibitors (TKls) monotherapy or TKI-IO combination therapy.
Authors: Pei Dong, Tingxuan Huang, Yulu Peng, Wensu Wei, Lijuan Jiang, Xi Zhong, Zhiling Zhang, Hui Han, Fangjian Zhou
Journal: Journal of Clinical Oncology (2024)

e16514 Background: Tyrosine kinase inhibitors (TKI) monotherapy or TKI in combination with immunotherapeutic agents (IO) are standard of care fist-line treatment for advanced or metastatic renal cell carcinoma (RCC). TKI monotherapy is extremely frequently in China because of the medicine Indications and health care policy. We examined the outcomes of patient treated with TKI in monotherapy and in combination with immunotherapy (TKI-IO) in Chinese patients. Methods: We performed a retrospective analysis of clinical outcomes in patients with RCC treated with TKI (cohort 1) or TKI-IO (cohort 2) in Sun Yat-sen Cancer Center between Dec 1,2015 and Nov 30,2022. Median follow-up was 26.1m (range from 0 to 87.6). Real-world progression free survival (1L-rwPFS), 2L-rwPFS and PFS2 (1L-rwPFS+2L-rwPFS),which means progression free survival from first-line treatment to second-line progression were calculated by Kaplan-Meier analysis and compared by the log-rank test. Cox proportional-hazard models were used to obtain hazard ratios (HRs) with 95%. Results: In total,325 patients were included. The median age was 55 (16-83), Male 75% (244), Female 25% (81). In cohort 1, 264 patients received 1L TKI and in cohort 2, 61 patients received 1L TKI-IO treatment. Median 1L-rwPFS in cohort1 was 7.7m VS 17.2m in cohort2 (HR 0.43 [0.32; 0.56]; p&lt;0.00001), amongst all patients, the TKI monotherapy most frequently prescribed was sunitinib, for TKI-IO, the most prescribed was axitinib plus Tislelizumab Injection. Median PFS2 was longer in TKI-IO (32.6m vs 24.8m) (HR 0.42 [0.27;0.66], p&lt;0.00001). In cohort 1, 37 patients progression with prior TKI monotherapy received 2L TKI therapy, while 211 patients received TKI-IO, median 2L-rwPFS was longer in 2L TKI-IO (14.2m vs 7.5m) (HR 0.52 [0.33;0.83], p=0.00043), PFS2 also had similar trend 20.3m VS 27m (HR 0.62 [0.40;0.96], p=0.0095). In 211 patients 2L TKI-IO cohort, the most prescribed was axitinib+IO (182/211), median 2L-rwPFS was 15.2m in axitinib+IO VS 8.2m in IO+other TKI (HR 0.41 [0.23;0.72], p&lt;0.00001).Data is contained in the table. Conclusions: Our retrospective cohort study suggests that TKI-IO provides a significant progression-free survival advantage over TKI monotherapy, whether used in the first-line or the subsequent line of therapy. Axitinib may be one of the best companions for immunotherapy. [Table: see text]
Genomic alterations and clinical outcomes in patients with non-clear cell RCC: Indiana University experience.
Authors: Fadi Taza, Mya Tran, Rebecca Hassoun, Sandra K. Althouse, Christopher A. Fausel, Bryan P. Schneider, Tareq Salous, Theodore F. Logan, Nabil Adra, Jennifer King
Journal: Journal of Clinical Oncology (2024)

e16506 Background: Non-clear cell RCC (nccRCC) represents a heterogeneous group of tumors with sparse data on the clinical features and genomic landscape. Here, we describe a real-world cohort of nccRCC patients, characterize the genomic makeup, and report on clinical outcomes utilizing contemporary therapeutic strategies. Methods: Patients with nccRCC treated at Indiana University and who underwent genomic sequencing between 2015-2023 were included in this analysis. Baseline demographic and disease characteristics were summarized. Kaplan-Meier method was used to analyze progression-free survival (PFS) and overall survival (OS) using the log rank test to compare groups. Results: 55 patients were included. The median age at diagnosis was 56 years. 48 patients (87%) had metastatic disease. 25 (45.5%) had de novo metastatic disease. The most common histology subtypes included were unclassified (n=18; 32.7%), papillary (n=14; 25.5%), chromophobe (n=6; 10.9%), translocation (n=5; 9.1%), renal medullary (n=3; 5.5%), collecting duct (n=3; 5.5%), and other (n=6; 11.0%). Rhabdoid and/or sarcomatoid features were present in 32% (n=18). First-line systemic therapy for metastatic disease was single agent tyrosine kinase inhibitor (TKI) in 14 patients (29.2%), combination immunotherapy (IO-IO) for 11 patients (23.0%), combination IO-TKI for 11 patients (23.0%), single agent IO for 2 patients (4.2%), cisplatin-gemcitabine in 5 (10%), and other in 5 patients (10%). Genomic alterations are summarized in the table. Overall, diverse mutations were detected across variant subtypes, including alterations in TP53, CDKN2A, NF2, chromatin modulation ( SETD2, BAP1, PBRM1), PI3K/AKT (PIK3CA, PTEN, mTOR), and VHL/HIF pathway. Median PFS was 0.6 (0.3-0.9) years. No statistical difference was observed in the median PFS between the histology subgroups. 2-year OS for chromophobe histology was 100%, unclassified was 62.2%, papillary was 56%, and other histologies was 40.4%. 2-year OS for all patients treated with IO-TKI was 85.7%, single agent TKI was 47.9%, IO-IO was 38.6%, and NE for single agent IO. Conclusions: In this real-world cohort of patients with nccRCC, unclassified histology had the highest frequency of the most common genomic alterations evaluated. There was a trend with improved 2-year OS for patients with chromophobe histology and patients treated with IO-TKI. [Table: see text]
Characterization of complete responders to nivolumab + gemcitabine-cisplatin vs gemcitabine-cisplatin alone and patients with lymph node–only metastatic urothelial carcinoma from the CheckMate 901 trial.
Authors: Matt D. Galsky, Guru P. Sonpavde, Thomas Powles, Melanie Claps, Mauricio Burotto, Michael Schenker, Juan Pablo Sade, Aristotelis Bamias, Philippe Beuzeboc, Jens Bedke, Jan Oldenburg, Yüksel Ürün, Ding-Wei Ye, Begoña Pérez Valderrama, Yoshihiko Tomita, Jeiry Filian, Lily Wang, Daniela Purcea, Michiel Simon Van Der Heijden
Journal: Journal of Clinical Oncology (2024)

4509 Background: In the CheckMate 901 trial, combination nivolumab (NIVO) + gemcitabine-cisplatin (GC) demonstrated significant improvements in overall survival (OS) and progression-free survival (PFS) with compelling objective response rates (ORR; 57.6% with NIVO+GC vs 43.1% with GC alone) and deep, durable complete responses (CR; 21.7% with NIVO+GC vs 11.8% with GC alone) in patients (pts) with previously untreated unresectable or metastatic urothelial carcinoma (mUC). Lymph node (LN)-only metastatic disease is a favorable prognostic factor in pts with mUC and a subset of pts achieve durable disease-free, treatment-free survival with GC +/- surgical consolidation. We conducted a post hoc analysis to characterize the subset of pts with CR, with further analysis of pts with LN-only mUC. Methods: In the global, open-label, randomized, phase 3 CheckMate 901 (NCT03036098) trial, cisplatin-eligible pts received NIVO 360 mg + GC every 3 wk for ≤6 cycles followed by NIVO 480 mg every 4 wk until disease progression/unacceptable toxicity or up to a maximum of 2 yrs, or GC every 3 wk for ≤6 cycles. Primary endpoints were OS and PFS by blinded independent central review (BICR). ORR per BICR and safety were exploratory endpoints. These post hoc analyses evaluated treatment outcomes in complete responders and in pts with LN-only disease. Results: Of the 608 pts randomized, 102 (16.8%) achieved a CR. Baseline disease characteristics of these pts are shown in the Table. As pts with LN-only mUC were enriched in the CR group, additional analysis of this subgroup was performed. Of all randomized pts, 54 treated with NIVO+GC and 56 treated with GC had LN-only mUC. In these pts, the ORR and CR rate was 81.5% (95% CI 68.6-90.7) and 63.0% versus 64.3% (50.4-76.6%) and 33.9% for NIVO+GC and GC, respectively. Median OS (95% CI) in LN-only pts was 46.3 (24.0-NE) mos with NIVO+GC vs 24.9 (21.4-29.9) with GC (HR, 0.58, 95% CI 0.34-1.00), and median PFS (95% CI) was 30.5 (9.6-NE) mos with NIVO+GC vs 8.8 (7.5-10.9) mos with GC (HR 0.38, 95% CI 0.22-0.66). Conclusions: NIVO+GC generated deep responses in CheckMate 901 with a fixed duration of chemotherapy and up to 2 years NIVO. Exploratory characterization of pts with CR identified a group of pts enriched with LN-only disease.In pts with LN-only mUC, NIVO+GC induced durable disease control and clinically meaningful improvements in OS and PFS vs GC alone. These results provide additional support for NIVO plus cisplatin-based chemo as a first-line treatment option for pts with mUC. Clinical trial information: NCT03036098 . [Table: see text]
Burden of non-muscle–invasive bladder cancer (NMIBC) leveraging a novel American Urological Association Quality Registry Qdata module: A real-world data analysis based on manual data abstraction.
Authors: Shannon Gallagher, Alyshah Abdul Sultan, Kathryn Sands, Iris Chin, Sarah Cote, Samuel Spigelman, Simona Baculea, Jennifer Bepple
Journal: Journal of Clinical Oncology (2024)

e16607 Background: Bladder cancer ranks among the most common cancers globally. At diagnosis, 75% of patients have non-muscle-invasive bladder cancer (NMIBC). However, there is limited evidence on the real-world burden of NMIBC by risk categories specified by the International Bladder Cancer Group (IBCG). Large routinely collected data lack reliable granular information on tumor size, multiplicity, grade, and recurrence history and can lead to misclassification. Methods: Electronic health record data from the American Urological Association (AUA) Quality (AQUA) Registry, which is a national Qualified Clinical Data Registry was leveraged within the de-identified NMIBC Qdata module to identify and risk stratify patients based on the updated IBCG guidance. This EHR-derived module was linked to Komodo Health claims to increase capture of procedures. A random sample (n=2,500) from approximately 54,000 study-eligible NMIBC patients within the overall database was identified between 2015 and 2022 with a valid T-stage reading anytime in their medical record. Information on relevant parameters (e.g., tumor size, multifocality, stage, grade) were manually abstracted based on a standard protocol and summarized. Abstraction quality was ensured through a comprehensive disease and study training and test cases in which the clinical abstractor met ³85% agreement with the gold standard. Audits were also performed on ³10% of cases. Results: Of the 501 records initially abstracted, 96% of patients had information on relevant parameters to classify them by risk based on the IBCG guidelines. At first presentation during the study period, the majority of patients were Ta (65%), whereas 8% and 27% presented as Tis and T1, respectively. During the observation period, 291 (65%) patients were classified as high-risk whereas 114 (24%) and 135 (28%) were ever classified as low and intermediate risk, respectively. For patients with intermediate risk NMIBC, the proportion of newly diagnosed versus recurrence was similar (50%). Conclusions: This study leveraged one of the largest US-created NMIBC databases to provide contemporary, real-world distribution of NMIBC risk founded on the updated IBCG guidance. The study demonstrates that a high proportion of NMIBC patients that have explicit tumor characteristics documented are classified as high risk followed by intermediate risk, warranting the need for innovative therapies in these patient groups.
Maintenance therapy with avelumab as the first-line treatment in patients with metastatic urothelial carcinoma: A real-world, ambispective RAVE-Bladder study.
Authors: Yana Gridneva, Alexander Sultanbaev, Yulia Anzhiganova, Mark Gluzman, Anastasia Mochalova, Alexey Shkurat, Elvira Parsadanova, Edgar Israelyan, Yulia Murzina, Aleksey Kalpinsky, Olesia Stativko, Elena Karabina, Artyom Kеln, Vladislav Petkau, Natalya Tovbik, Maria Turganova, Sufiia Safina, Evgeny Kopyltsov, Maria Volkova, Ilya Tsimafeyeu
Journal: Journal of Clinical Oncology (2024)

e16569 Background: The RAVE-Bladder study was designed to assess the efficacy and safety of avelumab maintenance in patients with metastatic urothelial carcinoma in a real-world population. Methods: In this non-interventional, ambispective study, eligible patients had metastatic urothelial carcinoma and measurable disease that had not progressed with first-line platinum-based chemotherapy. Patients received maintenance avelumab according to a standard regimen (800 mg, administered every 2 weeks). Tumor imaging was performed at baseline and then every 12 weeks. The primary endpoint was overall survival (OS) at the initiation of avelumab treatment, while secondary endpoints included progression-free survival (PFS), objective response rate (ORR), and safety. Results: At data cutoff (February 02, 2024), 110 patients (81% male, 19% female) were recruited from 21 sites and median follow-up was 9.71 months. Median age was 65 (range, 36-84) years. All patients had confirmed urothelial carcinoma (high grade, 62.8%). Primary tumor site was upper urinary tract in 26 (23.6%) and bladder in 84 (76.4%) cases. Forty-five (40.9%) patients had radical surgery; 68 (61.8%) had metastatic disease at time of diagnosis; 44 (40%) had 2 and more metastatic sites. First-line chemotherapy included gemcitabine + cisplatin, gemcitabine + carboplatin, cisplatin only, carboplatin only, and MVAC in 51 (46.4%), 32 (29%), 19 (17.3%), 7 (6.4%), and 1 (0.9%) patients, respectively. Median number of chemotherapy cycles was 4 (range, 3-9) and median number of avelumab infusions was 16 (range, 2-43). ORR to chemotherapy was 48.2%. An additional 38 patients (34.6%) responded to avelumab therapy (16 CR, 22 PR). Median OS was not reached and 1-year OS rate was 78.7%. Median PFS was 9.5 months (95% CI 7.8 – 11.2 months). Thirteen (11.8%) patients experienced grade 3 adverse events during avelumab therapy. Conclusions: The findings illustrate the favorable tolerability of maintenance therapy with avelumab, a remarkable progression-free interval subsequent to standard platinum-containing chemotherapy and prominent additional response rate among patients with metastatic urothelial carcinoma. Ongoing follow-up continues to provide additional insights. Clinical trial information: KCRB01012022 .