tbuckley/cabot-search huggingface dataset:
Cabozantinib outcomes for metastatic renal cell carcinoma at a tertiary NHS hospital in the United Kingdom (UK).
Authors: Guhan Arumugam Shanmugasundaram, Emily Holden, Hadeel Al-Husban, Farasat Kazmi, David Maskell, Gaurav Kapur
Journal: Journal of Clinical Oncology (2024)

e16538 Background: Kidney cancer remains the seventh most common solid organ cancer in the UK, USA and Europe, with renal cell carcinoma forming most of these cases [1]. In the UK, kidney cancer accounts for 3% of all new cancer diagnoses of which 25–31% present with metastatic RCC (mRCC) at initial diagnosis. [2] Methods: The METEOR trial was used as the comparator for response rates and progression-free survival to evaluate our outcomes. In the METEOR trial, treatment with Cabozantinib was associated with significantly better overall survival (OS) (21.4 months (m) with Cabozantinib vs 16.5m Everolimus), progression-free survival (PFS) (7.4m vs 3.9m), objective response rates (ORR) (17% vs 3%), and an equivalent safety profile when compared to Everolimus, a second-line treatment for patients with advanced renal cell carcinoma. [3] We present the results of Cabozantinib outcomes in the first to third line setting for mRCC at an NHS tertiary hospital. A direct comparison of OS is not feasible, as the METEOR data was for Cabozantinib in the second line. In contrast, Cabozantinib was used in first, second and subsequent line settings according to the NHS funding in our hospital trust. Results: From 16 April 2018 to 13 November 2023, 43 patients with mRCC received Cabozantinib at our NHS trust. Compared to the METEOR study, the median follow-up for our NHS tertiary centre patients was 7.5 m, as opposed to 18.7 m. Comparing the real-world data from our NHS centre with the METEOR trial, the ORR (partial response according to RECIST criteria) was 25% compared to 17%, whilst the PFS was 10.6m vs 7.4m. Interestingly, we observed that patients who had received immunotherapy before Cabozantinib had significantly better PFS (12m OS = 22% vs 0%; Log Rank = 0.03). Grade 3 and above toxicities was 32.5% vs 71% (NHS hospital vs METEOR trial). Conclusions: Overall, Cabozantinib showed better than expected response rates, and the toxicities in our NHS tertiary hospital were less severe than in the METEOR trial. Significantly, we observed that individuals who had received immunotherapy before Cabozantinib had higher survival outcomes. References: 1. U.S. Cancer Statistics Working Group. U.S. Cancer Statistics Data Visualizations Tool, based on 2022 submission data (1999-2020): U.S. Department of Health and Human Services, Centers for Disease Control and Prevention and National Cancer Institute; https://www.cdc.gov/cancer/dataviz , released in November 2023; 2. Cancer Research UK [Internet]. Kidney cancer statistics. Available from: http://www.cancerresearchuk.org/healthprofessional/cancer-statistics/statistics-by-cancer-type/kidney-cancer. [Cited: 2019 Jan 15]; 3. Choueiri, Toni K., et al. "Cabozantinib versus everolimus in advanced renal cell carcinoma (METEOR): final results from a randomised, open-label, phase 3 trial." The Lancet Oncology 17.7 (2016): 917-927.
Camrelizumab plus apatinib for previously treated advanced adrenocortical carcinoma: A single-arm, open-label, phase 2 trial.
Authors: Zhigong Wei, Yuchun Zhu, Lei Cai, Xingchen Peng
Journal: Journal of Clinical Oncology (2024)

4511 Background: Adrenocortical carcinoma (ACC) is a rare, aggressive malignancy with dismal prognosis. Therapeutic options for patients with advanced ACC after failure of standard treatments are limited. The clinical benefit of single-agent immunotherapy as second-line therapy was still unsatisfactory. Methods: This was an investigator-initiated, prospective, single-arm, open-label, phase 2 trial and conducted at a single medical center. Patients were eligible for inclusion if they were aged at least 18 years; were pathologically diagnosed as unresectable or metastatic ACC; had failed first-line therapy; had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1; had at least one measurable lesion; and had adequate organ function. The key exclusion criteria included a history of treatment with immunotherapy, anti-angiogenic small molecule TKIs, or anti-angiogenic monoclonal antibodies; a history of uncontrolled hypertension; and a history of an autoimmune condition requiring systemic therapy. All study participants received camrelizumab 200 mg intravenously on the first day of each 3 week cycle, combined with apatinib 250 mg orally once per day until disease progression, unacceptable toxicity, or withdrawal of consent. The primary endpoint was objective response rate (ORR), defined as the proportion of participants with complete response (CR) or partial response (PR) per RECIST (version 1.1). Results: A total of 21 patients with advanced ACC received at least one dose of camrelizumab and apatinib. ORR was 52% (95% CI, 30 to 74), and the disease control rate was 95% (95% CI, 84 to 100), superior to PD-1 inhibitor monotherapy and first-line standard therapy. The median PFS was 12.6 months (95% CI, 8.4 to 20.9), and the median OS was 20.9 months (95% CI, 11.0 to 20.9). The most common grade 3—4 treatment-related adverse events were alanine aminotransferase elevation (28.6%), aspartate aminotransferase elevation (23.8%) and lymphopenia (23.8%). Our exploratory analysis showed higher peripheral blood CXCR3+CD8+ T cell abundance, lower immunosuppressive CD4+ T cell abundance, and higher overlap of clonotypes between tumor-infiltrating T cells and circulating T cells, likely related to preferable response to camrelizumab plus apatinib therapy. Conclusions: In conclusion, the combination of camrelizumab with apatinib showed promising activity and acceptable toxicity in advanced ACC patients who failed previous lines of therapy. Pre-treatment peripheral blood immune cell subsets could be regarded as potential predictors of efficacy. Given the promising clinical activity, the potential of camrelizumab with apatinib as first-line therapy for advanced ACC need further evaluated. Clinical trial information: NCT04318730 .
A phase II study of lurbinectedin with or without avelumab in small cell carcinoma of the bladder (LASER).
Authors: Nicholas I. Simon, Elias Chandran, Scot Anthony Niglio, Andre Rashad Kydd, Saad Omar Atiq, Lisa Ley, Tzu-fang Wang, Salah Boudjadi, Elizabeth Smith, Dilara Akbulut, Seth M. Steinberg, Andrea B Apolo
Journal: Journal of Clinical Oncology (2024)

TPS4629 Background: Small cell carcinoma of the bladder (SCCB) is a rare, aggressive malignancy accounting for &lt;1% of all bladder malignancies. Given its rarity, few prospective randomized trials have been completed in SCCB. Most therapeutic evidence comes from retrospective case series and due to its histologic similarity to small cell lung cancer (SCLC), current guidelines recommend bladder cancers with any component of small cell histology be treated similarly to SCLC. Lurbinectedin is a novel alkylating agent which recently received accelerated approval from the FDA as a second line treatment for SCLC after demonstrating an overall response rate (ORR) of 35.2% and median duration of response (DoR) of 5.3 months (Trigo et al., Lancet Oncol, 2020). Avelumab is an anti-PD-L1 antibody FDA approved as maintenance treatment for patients with locally advanced or metastatic urothelial cancer (UC) without progression on frontline chemotherapy. Case reports have demonstrated that second line options in SCLC, including immunotherapy, appear to have some efficacy in SCCB. The purpose of this study is to assess the efficacy of lurbinectedin, either alone or in combination with avelumab, in participants with SCCB or other high grade neuroendocrine tumors (HGNETs) of the urinary tract. Methods: LASER (NCT06228066) is a phase II, multisite, open label, nonrandomized study with two cohorts. Eligible patients must have pathologically confirmed SCCB or other HGNETs of the urinary tract. Patients with mixed histologies, with any component of neuroendocrine tumor, are eligible. Patients must have received or be ineligible/refused frontline platinum/etoposide therapy. Participants in Cohort 1 must have received prior immune checkpoint inhibitors (ICIs) or be ineligible for treatment with ICI. These patients will receive lurbinectedin 3.2mg/m2 IV every 21 days. Participants in Cohort 2 must be ICI naïve but eligible to receive them. These patients will receive lurbinectedin 3.2mg/m2 IV and avelumab 800mg IV every 21 days. The primary endpoint for both cohorts is ORR, with key secondary endpoints including clinical benefit rate, PFS, OS, and DoR. The study will be conducted using a Simon minimax two stage design to rule out an ORR of 5% in favor of an ORR of 25% or greater in each cohort. If 1 of the first 12 patients has a response accrual will continue up to 16 evaluable patients per cohort. Accrual ceiling will be set at 35 patients. Exploratory objectives include analyzing peripheral immune subsets, DNA and RNA sequencing of tumors, and measurement of ctDNA and CTCs. Clinical trial information: NCT06228066 .
Association of race with clinical outcomes in patients with advanced renal cell carcinoma (aRCC) treated with immune checkpoint inhibitors (ICIs).
Authors: Yujin Choi, Ahmet Yildirim, Mengting Wei, Yuan Liu, Rohit Vivek Goswamy, Jacqueline T. Brown, Bassel Nazha, Dylan J. Martini, Caitlin Hartman, Greta Russler McClintock, Tony Zhuang, Haydn Kissick, Wayne B. Harris, Bradley Curtis Carthon, Omer Kucuk, Viraj A. Master, Mehmet Asim Bilen
Journal: Journal of Clinical Oncology (2024)

e16539 Background: Race has been regarded to be associated with clinical outcome of aRCC patients undergoing therapy with ICIs, but larger data is still limited. Here, we evaluated race and clinical outcome in aRCC patients treated with ICI. Methods: A retrospective analysis was conducted on adult patients with aRCC treated with ICIs at Emory Winship Cancer Institute between 1/1/2018 and 8/31/23. Overall survival (OS) and progression-free survival (PFS) was calculated from the date of treatment initiation to death and progression, respectively. Progression was determined by RECIST v1.1 or clinical progression. Clinical benefit (CB), including stable disease, partial response, and complete response, was determined by RECIST v.1.1. Univariate (UVA) and multivariate (MVA) analyses were conducted for CB, OS, and PFS in patients to assess the association with race. Results: There was a total of 401 patients, consisted of 71.1% White patients, 21.2% African American patients, and 7.7% patients with other racial profiles. Median age was 66 (range = 18-95). Treatment plan involved 139 (34.6%) patients for single ICI therapy, 131 (32.6%) patients for ICI/ICI therapy, 108 (26.9%) patients for ICI/TKI (tyrosine kinase inhibitor) therapy, 6 (1.5%) patients for ICI/ICI/TKI therapy, and 17 (4.23%) patients for therapy with ICI plus an experimental drug. Race was significantly associated with the CB, OS, and PFS of the patients in the UVA. African American patients demonstrated worse clinical outcomes with hazard ratios (HR) significantly less than 1 for both OS and PFS and odds ratios (OR) significantly greater than 1 for CB. According to the Kaplan-Meier plots, the median OS for African American and White patients were 17.1 and 34.8 months, respectively. Similarly, median PFS for African American, White, and patients of other races were 3.6, 7.7, and 13.9, respectively. MVA also suggested greater clinical benefit for patients of White and other racial backgrounds when compared to African American patients. Conclusions: The significant difference in clinical outcomes between the racial profile of patients suggest that African American patients may have worse clinical outcomes in treatment involving ICIs. A more in-depth analysis of race’s association with clinical outcomes can be conducted to assist with treatment plan decisions in the future. [Table: see text]
Efficacy and safety of first-line TKI plus ICI therapy in metastatic non-clear cell renal cell carcinoma: A real-world multiple-centre study.
Authors: Xi Zhong, Tingxuan Huang, Yulu Peng, Cheoklong NG, Xuhao Liu, Taile Jing, Wensu Wei, Zhiling Zhang, Hui Han, Minfeng Chen, Liru He, Jiwei Huang, Pei Dong
Journal: Journal of Clinical Oncology (2024)

e16519 Background: The combination of immune checkpoint inhibitor (ICI) and tyrosine kinase inhibitor (TKI) has emerged as the standard first-line therapy for metastatic renal cell carcinoma (mRCC), however, limited clinical trials have investigated the role of ICI plus TKI in the treatment of metastatic non-clear cell renal carcinoma (mnccRCC) for its heterogeneity and low incidence. Our study presents multiple center real-world data with the optimal sample size so far to assess the efficacy and safety profile of ICI plus TKI in patients with mnccRCC. Methods: We performed a retrospective analysis including patients previously untreated with mnccRCC receiving TKI plus ICI or TKI in four institutions participated in this study. The primary endpoint was progression-free survival (PFS) according to the Response Evaluation Criteria in Solid Tumors version 1.1, others including overall survival (OS), the objective response rate (ORR) and treatment related adverse events (AEs). Results: A total of 214 patients were included for this study with 122 patients receiving TKI monotherapy and 92 patients receiving TKI plus ICI. Median follow-up time was 29.4 months (IQ1-IQ3, 15.7-48.5). The median age of patients was 49 years, with the majority being male (70.6%) and intermediate/poor risk. The most prevalent pathological subtype of nccRCC was papillary RCC (44.4%), followed by MIT family translocated RCC (16.4%), fumarate hydratase RCC (10.3%), chromophobe RCC (9.3%), other nccRCC (6.5%), and unclassified RCC (13.1%). The median PFS of the TKI monotherapy group and the TKI plus ICI combination group were 5.9 months (95%[CI], 4.3-7.5) versus 15.2 months (95%CI, 6.6-23.7), while mOS was 38.5 months (IQ1-IQ3=17.1-70.0) for TKI cohort and unreached (IQ1-IQ3=23.4-N) in TKI plus ICI cohort. The ORR and disease control rate (DCR) was 16.4% versus 29.4% and 48.4% versus 78.3% in the two cohorts. Any grade of AEs was 93.44% and 96.74% occurred in the monotherapy group and combination therapy group, while the incidence of grade ≥3 AEs was 23.77% and 35.87%, respectively. Conclusions: The findings from our retrospective real-world cohort of mnccRCC patients demonstrate that the combination of ICI plus TKI could significantly enhance PFS, ORR and OS compared to TKI monotherapy and no new safety signals were found. [Table: see text]
Prognostic utility of YBX1-mediated genes in clear cell renal cell carcinoma outcomes.
Authors: Waleed Ali, Karine Tawagi, Andre Balla
Journal: Journal of Clinical Oncology (2024)

e16510 Background: The Y-box-binding protein1 (YBX1) transcription factor has been linked to a variety of biological processes such as mRNA stabilization and localization and cell-cycle progression. YBX1 has been shown to have pro-oncogenic effects in some cancers, possibly also modulating cisplatin’s effects in others. However, comparatively less regarding YBX1 has been explored in kidney renal clear cell carcinoma (ccRCC), the most common kind of kidney cancer. This in silico study explores the relationship between YBX1 and associated regulatory targets in ccRCC cases. Methods: The MSig database was utilized to generate a list of genes which contained one or more YBX1 binding sites in their promoter region based on ChIP-seq data. Kaplan-Meier plots of overall survival in ccRCC cases based on YBX1 and YBX1-regulated gene expression were generated using TCGA data on the KMPlot platform with “high” and “low” expression cutoffs based on quartiles. Multiple hypothesis testing was corrected by adjusting the significant p-value cutoff to a FDR &gt;0.05 (adjusted p-value cutoff is 0.023). Enrichment and network analysis was then conducted on genes shown to be differentially expressed in respect to outcome through the Cytoscape and Metascape platform to see which over-represented biological pathways may mediate outcome (p&lt;0.01 for significance). Results: Out of 76 initial genes, 33 showed differential expression in regards to survival, including YBX1 itself. Enrichment analysis highlighted biological processes such as negative regulation of mRNA metabolic processes and Nop56p-associated rRNA complex formation as possible ways YBX1 and its related targets can affect outcomes. A variety of genes were highlighted by the network analysis, such as the membrane trafficking gene YIF1A and acetyltransferase KAT8 among others. Conclusions: Similar to what has been shown in other types of cancers, YBX1 and its regulatory constituents have been linked to ccRCC outcomes, possibly due to its role regarding mRNA regulation as highlighted by our enrichment analysis. Other interactions mediated by genes such as the cell cycle regulator CCAR2 offer other pathways through which YBX1 can mediate outcome. Previously being linked with cisplatin resistance in other cancers such as breast, YBX1 offers a suitable target for further wet-lab research regarding its role in ccRCC.
Cabozantinib (CABO) after prior immune checkpoint inhibitor (ICI) and tyrosine-kinase inhibitors (TKI) therapy in metastatic renal cell carcinoma (mRCC): Real-world evidence (RWE) from a Moscow observational program.
Authors: Natalya Polshina, Daria Filonenko, Sofia Karulina, Lyudmila Zhukova
Journal: Journal of Clinical Oncology (2024)

e16526 Background: Cabozantinib is approved for metastatic renal cell carcinoma (mRCC). Data of CABO efficacy after prior ICI/ICI-TKI therapy are limited by several RWE trials. Here we report real-world evidence of CABO in Russian patients from a Moscow observational program. Methods: Patients (pts) with mRCC treated with CABO monotherapy through the Moscow observational prospective program between Feb’2022 and Jan’2024 were identified. All pts received 1-3 prior lines of therapy, all received prior ICI and TKI, either in combination or consequently. Pts with active CNS metastases were excluded from the program. Baseline clinical and treatment characteristics were collected. Rates of partial response (PR), stable disease (SD), progressive disease (PD), and disease control rate (DCR, PR+SD) were analyzed, and survival outcomes (overall survival (OS) and progression-free survival (PFS)) were calculated. Results: A total 59 patients (pts) treated with CABO were included in our analysis. Median age was 59 years (range 40-78), 46 (78%) pts were male, 54 (91,5%) pts had clear-cell histology. At time of CABO start 5 pts (8,5%) had the ECOG PS 0, 37 pts (62,7%) had ECOG PS 1, 17 pts (28,8%) had ECOG PS 2. 40 pts (67,8%) had intermediate International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk, 19 pts (32,2%) had poor IMDC risk. 45 (76,3%) pts had prior nephrectomy. 15 pts (25,4%), 27 pts (45,8%), 17 pts (28,8%) had 1, 2 and ≥3 previous treatment lines respectively; 22 pts (37%) received prior treatment with combination of ICI and TKI. 4 pts (7%), 26 pts (44%), 29 pts (49%) had 1, 2-3 and &gt; 3 sites of metastases respectively. 31 pts (53%) had bone metastases. Median (min-max) follow-up was 14 (1-22) months (mo). Rates of best response were: PR - 20%, SD - 56%, PD - 19%. Overall DCR was 76%. Median PFS was 14 mo (12,3-15,7) with 12-mo PFS 59%. Median OS was not reached, and the 12-mo OS rate was 76%. 41% of patients had a dose reduction, 32% needed treatment interruption and 19% of pts discontinued treatment due to toxicity. Conclusions: The effectiveness of CABO observed in this real-world observational program was consistent with results from clinical trials: DCR – 76%, median PFS – 14 mo with 12-mo PFS 59% and 12-mo OS 76%. Dose modifications may be required to optimize CABO use in routine clinical practice.
Avelumab + axitinib vs sunitinib in patients (pts) with advanced renal cell carcinoma (aRCC): Final overall survival (OS) analysis from the JAVELIN Renal 101 phase 3 trial.
Authors: Robert J. Motzer, Konstantin Penkov, Hirotsugu Uemura, Matthew T Campbell, Christian K. Kollmannsberger, Jae-Lyun Lee, Balaji Venugopal, Alfonsus Van Den Eertwegh, Sylvie Negrier, Howard Gurney, Laurence Albiges, Raanan Berger, John Haanen, Brian I. Rini, James Larkin, Manuela Schmidinger, Robin Sandner, Jing Wang, Alessandra Di Pietro, Toni K. CHOUEIRI
Journal: Journal of Clinical Oncology (2024)

4508 Background: The JAVELIN Renal 101 (NCT02684006) phase 3 trial compared first-line treatment with avelumab + axitinib vs sunitinib in aRCC. The trial previously met one of its primary objectives by showing significantly longer progression-free survival (PFS) with avelumab + axitinib vs sunitinib in pts with PD-L1+ tumors; longer PFS, higher objective response rate (ORR), and an acceptable safety profile were also observed in the overall population. OS data were immature. Here we report the final analysis. Methods: Pts with untreated aRCC (any IMDC risk score) were randomized 1:1 to avelumab + axitinib or sunitinib. OS and PFS (by blinded independent central review) in pts with PD-L1+ tumors (SP263 assay) were independent primary endpoints. OS and PFS in the overall population were key secondary endpoints; response and safety were also analyzed. Results: Of 886 pts randomized, 560 (63.2%) had PD-L1+ tumors. At data cutoff (August 31, 2023), median follow-up in the avelumab + axitinib and sunitinib arms was 73.7 and 73.6 months, respectively (≥68 months in all pts). Final efficacy data are shown in the Table. In the avelumab + axitinib and sunitinib arms, grade ≥3 TRAEs occurred in 66.8% vs 61.5%, respectively. Second-line therapy was received by 58.1% vs 69.4%, including a PD-(L)1 inhibitor in 18.8% vs 53.6%, respectively. Conclusions: The JAVELIN Renal 101 trial provides the longest follow-up for immune checkpoint inhibitor + tyrosine kinase inhibitor combination treatment from a phase 3 trial reported to date. OS analyses favored avelumab + axitinib vs sunitinib but did not reach statistical significance. PFS was longer with avelumab + axitinib vs sunitinib, and responses were durable in a subset of pts. Final analysis results confirm the long-term efficacy and manageable safety profile of avelumab + axitinib treatment in pts with aRCC. Clinical trial information: NCT02684006 . [Table: see text]