Purpose: The role of circulating cell-free tumor DNA (ctDNA) as an adjunct to tissue genomic profiling is poorly defined in metastatic renal cell carcinoma (mRCC). In this study, we aim to validate previous findings related to genomic alteration (GA) frequency in ctDNA and determine the concordance between ctDNA and tissue-based profiling in patients with mRCC. Experimental Design: Results of 839 patients with mRCC who had ctDNA assessment with a Clinical Laboratory Improvement Amendments (CLIA)-certified ctDNA assay between November 2016 and December 2019 were collected. Tissue-based genomic profiling was collected when available and concordance analysis between blood- and tissue-based testing was performed. Results: ctDNA was assessed in 839 patients (comprising 920 samples) with mRCC. GAs were detected in 661 samples (71.8%). Tissue-based GAs were assessed in 112 patients. Limiting our analyses to a common 73-/74-gene set and excluding samples with no ctDNA detected, a total of 228 mutations were found in tissue and blood. Mutations identified in tissue (34.7%; 42/121) were also identified via ctDNA, whereas 28.2% (42/149) of the mutations identified in liquid were also identified via tissue. Concordance between ctDNA and tissue-based profiling was inversely related to the time elapsed between these assays. Conclusions: This study confirms the feasibility of ctDNA profiling in the largest mRCC cohort to date, with ctDNA identifying multiple actionable alterations. It also demonstrates that ctDNA and tissue-based genomic profiling are complementary, with both platforms identifying unique alterations, and confirms that the frequency of unique alterations increases with greater temporal separation between tests.

Papillary renal cell carcinoma (pRCC) is the second-most common subtype of kidney cancer following clear cell renal cell carcinoma (ccRCC), representing 15% of kidney cancers. Despite advances in therapy, including combination strategies with targeted therapies and immune checkpoint inhibitors, progress has lagged behind that of ccRCC. This is in part due to the heterogenous nature of the various subtypes of pRCC. More recently, investigators have turned efforts towards histology and biology-based trials. In this review, we outline some of the distinct biological characteristics of pRCC and discuss the most impactful clinical trials to date. Finally, we look ahead to several highly anticipated ongoing trials in pRCC.

Targeted therapy has shown to be a very effective treatment in tumors with specific genomic drivers. Trk has proven to be one such target. Efforts to target the Trk fusion with specific inhibitors ... Lay abstract Advances in medical science has allowed us to analyze genes within cancer cells and target abnormal genes more precisely. One such target is called NTRK, which carries genetic informat...

Objectives: To characterise the restrictiveness of eligibility criteria in contemporary renal cell carcinoma (RCC) trials, using recommendations from the American Society of Clinical Oncology (ASCO)‐Friends of Cancer Research (FCR) initiative. Methods: vPhase I–III trials assessing systemic therapies in patients with RCC starting between 30 June 2012 and 30 June 2022 were identified. Eligibility criteria regarding brain metastases, prior or concurrent malignancies, hepatitis B virus (HBV) or hepatitis C virus (HCV) infection, and human immunodeficiency virus (HIV) infection were identified and stratified into three groups: exclusion, conditional inclusion, and not reported. Descriptive statistics were used to determine the frequency of eligibility criteria. Fisher's exact test or chi‐square test were used to calculate their associations with certain trial characteristics. Results: A total of 423 RCC trials were initially identified of which 112 (26.5%) had sufficient accessible information. Exclusion of patients with HIV infection, HBV/HCV infection, brain metastases, and prior or concurrent malignancies were reported in 74.1%, 53.6%, 33.0%, and 8.0% of trials, respectively. In the context of HIV and HBV/HCV infection, patients were largely excluded from trials evaluating immunotherapy (94.4% and 77.8%, respectively). In addition, brain metastases were excluded in trials assessing targeted therapy (36.4%), combined therapy (33.3%), and immunotherapy (22.2%). Exclusion of patients with prior or concurrent malignancies was less frequently reported, accounting for 9.1%, 8.3%, and 5.6% targeted therapy, combined therapy and immunotherapy trials, respectively. Conclusion: A substantial proportion of RCC trials utilise restrictive eligibility criteria, excluding patients with fairly prevalent comorbidities. Implementing the ASCO‐FCR recommendations will ensure resulting data are more inclusive and aligned with patient populations in the real‐world.

11052Background: Trabectedin (T) is an anti-tumor agent used in the treatment of advanced soft-tissue sarcomas (STS). It interferes with DNA replication, causing double strand breaks and apoptosis, and may deplete tumor-associated macrophages in the tumor microenvironment. T was recently USFDA- approved for advanced liposarcoma and leiomyosarcoma. We report the largest known single-center experience in advanced soft-tissue sarcoma treated with T. Methods: This retrospective study includes 442 advanced STS patients treated with T from 2005-2015 as part of various clinical trials. Baseline characteristics and treatment outcomes by histologic subtypes were assessed by RECIST 1.1 criteria. Progression-free survival (PFS) in months was determined in evaluable patients who completed at least 2 cycles of T, and had a follow-up CT scan or MRI. Results: The table shows the demographics and PFS of various subtypes of sarcoma. The median PFS for advanced leiomyosarcoma and liposarcoma (3.7 and 4.3 months respectivel...