Clinical Impact of the CARMENA Trial on Cytoreductive Nephrectomy Practices in the USA: A Difference-in-differences Analysis.

BACKGROUND AND OBJECTIVE: It is unclear whether cytoreductive nephrectomy (CN) practices have changed in the USA after the publication of the Cancer du Rein Métastatique Nephrectomie et Antiangiogéniques (CARMENA) trial in 2018. Our primary objective is to determine the effect of the CARMENA trial on CN rates in the USA. METHODS: Patients were identified in the National Cancer Database from 2004 to 2020. A quasiexperimental difference-in-differences analysis was used to test the primary outcome, as follows: the change in CN rate was assessed among metastatic clear cell renal cell carcinoma (ccRCC) patients diagnosed before versus after 2018, while using the localized nephrectomy (LN) rate performed in the setting of nonmetastatic ccRCC as a control group. KEY FINDINGS AND LIMITATIONS: The difference-in-differences analysis identified a statistically significant decrease in CN rate after CARMENA (ß-coefficient [standard error]: -0.06 [0.025], p = 0.028), with a 10.2% absolute and a 31.8% relative rate reduction when compared with the counterfactual (expected) value (34.7% â†’ 21.9% [actual] vs 32.1% [expected]). Primarily, relative differences in CN and LN rates before and after 2018 may be attributable to additional factors, aside from CARMENA publication, not tested in this quasiexperimental model. CONCLUSIONS AND CLINICAL IMPLICATIONS: CN rates decreased significantly after the publication of the CARMENA trial in 2018, with a minimal difference in regional or demographic practice patterns. Overall, the publication of the CARMENA trial results is seemingly associated with substantial alteration of clinical practice in the USA, with relatively broad and nonspecific adoption across facilities, regions, and demographics. PATIENT SUMMARY: For decades, the immediate surgical removal of the kidney tumor (cytoreductive nephrectomy) was a mainstay of metastatic kidney cancer treatment. In 2018, the CARMENA study showed that patients treated with systemic therapy alone had similar outcomes to patients who underwent cytoreductive nephrectomy first. In this study, we show that fewer cytoreductive nephrectomies were performed after the CARMENA trial results were published.

Cabozantinib Plus Nivolumab in Adult Patients with Advanced or Metastatic Renal Cell Carcinoma: A Retrospective, Non-Interventional Study in a Real-World Cohort/GUARDIANS Project.

INTRODUCTION: Combinations of immune-checkpoint inhibitors (ICIs) are the standard of care (SOC) for treatment-naive metastatic renal cell carcinoma (mRCC) patients. In this multicenter study, we evaluated the RW safety and efficacy of cabozantinib plus nivolumab in mRCC patients. METHODS: Data were retrospectively collected from twelve cancer centers in Germany, Switzerland, and Austria. Patients with advanced or mRCC were eligible. The investigator-based objective response rate (ORR) and progression free survival (PFS) were calculated from the start of the treatment to progression or death. Descriptive statistics and Kaplan-Meier (KM) plots were utilized where appropriate. RESULTS: In total, 96 eligible patients (66.6% male) with a median age of 66.0 years were included. The most common histology was clear-cell RCC (ccRCC) in 63.4% (n = 61). A prior nephrectomy was performed in 60.4% (n = 58). ECOG 0-1 was 68.8% (n = 66). A partial response was documented in 43.8% of patients (n = 42), a stable disease in 32.3% (n = 31), and a progressive disease in 8.3% (n = 8) as the best overall response. Response data were not evaluable in 13.5% (n = 13). The median follow-up time was 12.7 months (95% CI, 10.0-15.3). The PFS rate at 6 months was 89.8% in the overall population (86.8% for ccRCC; 90.0% for non-ccRCC). Adverse events (AEs) were reported in 82.3% (n = 79) for all grades and 41.7% (n = 40) for grades 3-5. Elevated liver enzymes (34.4%), diarrhea (31.3%), and hand-foot syndrome (29.2%) were the three most frequent AEs of any grade and causality. DISCUSSION/CONCLUSIONS: In this real-world cohort of mRCC patients, the application of cabozantinib plus nivolumab was shown to be safe and feasible. Our data support the use of cabozantinib plus nivolumab as a first-line standard therapy in mRCC patients. Major limitations were the retrospective data capture and short follow-up time of our study.

Optimal sequential therapy using tyrosine kinase inhibitors as the first-line treatment in patients with metastatic renal cell carcinoma: A nationwide multicenter study.

Objective: The purpose of the study was to identify the best sequence of therapy beginning with a tyrosine kinase inhibitor (TKI) as the first-line therapy for patients with metastatic renal cell carcinoma (mRCC) in terms of overall survival (OS), progression-free survival (PFS), and rates of discontinuation and adverse effects during the treatment period. Methods: This is a retrospective, nationwide multicenter study of patients with mRCC after diagnosis at 10 different tertiary medical centers in Korea from January 1992 to December 2017. We focused on patients at either "favorable" or "intermediate" risk according to the International mRCC Database Consortium criteria, and they were followed up (median 335 days). Finally, a total of 1409 patients were selected as the study population. We generated a Cox proportional hazard model adjusted for covariates, and the different therapy schemes were statistically tested in terms of OS as well as PFS. In addition, frequencies of discontinuation and adverse events were compared among the therapy schemes. Results: Of the primary patterns of treatment sequences (24 sequences), "sunitinib-pazopanib" and "sunitinib-everolimus-immunotherapy" showed the most beneficial results in both OS and PFS with significantly lower hazards than "sunitinib", which is the most commonly treated agent in Korea. Considering that the "TKI-TKI" structure showed relatively higher discontinuation rates with higher adverse effects, the overall beneficial sequence would be "sunitinib-everolimus-immunotherapy". Conclusion: Among several sequential therapy starting with TKIs, "sunitinib-everolimus- immunotherapy" was found to be the best scheme for mRCC patients with "favorable" or "intermediate" risks.

Prognostic value of type of prior TKI in pretreated metastatic renal cell carcinoma patients receiving nivolumab.

Aim: To define the prognostic significance of first-line TKI in mRCC patients receiving nivolumab.Materials and methods: A total of 571 mRCC patients who received ≥second line nivolumab were included in this subanalysis. The correlation between prior TKI (sunitinib vs. pazopanib) and overall response rate (ORR), disease control rate, progression-free survival and overall survival were investigated. Additionally, the impact of TKI choice according to the International Metastatic RCC Database Consortium prognostic score was examined.Results: There was no significant difference between sunitinib and pazopanib groups in terms of mPFS, mOS, overall response rate and disease control rate. Moreover, no difference between sunitinib and pazopanib was found according to the International Metastatic RCC Database Consortium prognostic score.Conclusion: There is no conclusive evidence favoring pazopanib or sunitinib treatment before initiating nivolumab therapy in metastatic renal cell carcinoma patients.

[Box: see text].

Final Analysis of a Noninterventional Study on Cabozantinib in Patients With Advanced Renal Cell Carcinoma After Prior Checkpoint Inhibitor Therapy of the German Interdisciplinary Working Group on Renal Tumors (IAG-N).

BACKGROUND: Efficacy of treatment after failure of check point inhibitors (ICI) therapy remains ill-defined in metastatic renal cell carcinoma (mRCC). OBJECTIVE: To evaluate the safety and effectiveness of cabozantinib after failure of ICI-based therapies. DESIGN, SETTING AND PARTICIPANTS: Patients with mRCC who concluded cabozantinib treatment directly after an ICI-based therapy were eligible. Data was collected retrospectively from participating sites in Germany. INTERVENTIONS: Cabozantinib was administered as a standard of care. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Adverse events (AE) were reported according to CTCAE v5.0. Objective response rate according to RECIST 1.1 and Progression Free Survival (PFS) were collected from medical records. Descriptive statistics and Kaplan-Meyer-plots were utilized. RESULTS AND LIMITATIONS: About 56 eligible patients (71.4% male) with median age of 66 years and clear cell histology in 66.1% (n = 37) were analyzed. 87.5% (n = 49) had ≥ 2 previous lines. IMDC risk was intermediate or poor in 17 patients (30.4%) and missing in 66.1%. 20 patients (35.7%) started with 60 mg. 55.4% (n = 31) required dose reductions, 26.8% (n = 15) treatment delays and 1.8% (n = 1) treatment discontinuation. Partial response was reported in 10.7% (n = 6), stable and progressive disease were reported in 19.6% (n = 11) and in 12.5% (n = 7). 32 patients were not evaluable (57.1%). Median treatment duration was 6.1 months. Treatment related AE were reported in 76.8% (n = 43) and 19.6% (n = 11) had grade 3-5. Fatigue (26.8%), diarrhea (26.8%) and hand-foot-syndrome (25.0%) were the 3 most frequent AEs of any grade and causality. SAE were reported in 21.4% (n = 12), 2 were fatal. Major limitation was the retrospective data capture in our study. CONCLUSIONS: Cabozantinib followed directly after ICI-based therapy was safe and feasible. No new safety signals were reported. A lower starting dose was frequently utilized in this real-world cohort, which was associated with a favorable tolerability profile. Our data supports the use of cabozantinib after ICI treatment.

Predicting Survival of Metastatic Clear Cell Renal Cell Cancer Treated with VEGFR-TKI-Based Sequential Therapy.

(1) Objective: To develop a clinically useful nomogram that may provide a more individualized and accurate estimation of cancer-specific survival (CSS) for patients with clear-cell (CC) metastatic renal cell carcinoma (mRCC) treated with nephrectomy and vascular endothelial growth factor receptor-tyrosine kinase inhibitor (VEGFR-TKI)-based sequential therapy. (2) Methods: A prospectively maintained database of 145 patients with mRCC treated between 2008 and 2018 was analyzed to predict the CSS of patients receiving sunitinib and second- and third-line therapies according to current standards of practice. A nomogram based on four independent clinical predictors (Eastern Cooperative Oncology Group status, International Metastatic RCC Database Consortium score, the Morphology, Attenuation, Size and Structure criteria and Response Evaluation Criteria in Solid Tumors response criteria) was calculated. The corresponding 1- to 10-year CSS probabilities were then determined from the nomogram. (3) Results: The median age was 60 years (95% CI 57.9-61.4). The disease was metastatic at diagnosis in 59 (40.7%), and 86 (59.3%) developed metastasis during follow-up. Patients were followed for a median 48 (IQR 72; 95% CI 56-75.7) months after first-line VEGFR-TKI initiation. The concordance probability estimator value for the nomogram is 0.778 ± 0.02 (mean ± SE). (4) Conclusions: A nomogram to predict CSS in patients with CC mRCC that incorporates patient status, clinical risk classification and response criteria to first-line VEGFR-TKI at 3 months is presented. This new tool may be useful to clinicians assessing the risk and prognosis of patients with mRCC.

A red blood cell-based score in the prognostication of patients with metastatic RCC of the Meet-URO 15 study.

Aims: Anemia, mean corpuscular volume and red cell distribution width may have some effects on survival outcomes of metastatic renal cell carcinoma (mRCC) patients and are incorporated in a red blood cell (RBC)-based score. Its validity in prognostication of mRCC patients treated with second-line nivolumab was assessed. Patients and methods: Retrospective analysis using Meet-URO-15 cohort of mRCC patients receiving nivolumab in the second-line setting or beyond. Outcomes were overall survival (OS) and progression-free survival (PFS). Results: A total of 390 patients were included. Significant differences in OS and PFS between RBC-based score groups, with group 1 (2 or 3 of the RBC-related prognostic factors) having longer OS (median 29.5 months, 95% CI: 23.1-35.9, versus 11.5 months, 95% CI: 8.5-22.6; p < 0.001) and PFS (7.5 months, 95% CI: 5.5-10.2, versus 4.2 months, 95% CI: 3.3-5.9; p = 0.040) than those in group 0 (0 or 1 RBC-related prognostic factors). Belonging to group 1 independently predicted OS (hazard ratio: 0.65, 95% CI: 0.50-0.85; p = 0.002) but not PFS (hazard ratio: 0.89, 95% CI: 0.70-1.14, p = 0.370) or disease response (OR 0.68, 95% CI: 0.41-1.10; p = 0.118) at multivariable analysis. Conclusion: RBC-based group scores independently predicted OS in mRCC patients treated with nivolumab.

This study looked at how certain blood cell measurements (anemia, mean corpuscular volume, red cell distribution width) affect survival in patients with metastatic renal cell carcinoma who are treated with nivolumab, an immunotherapy drug. Researchers analyzed data from 390 patients who received nivolumab as a second-line treatment or beyond. They divided patients into groups based on their blood cell scores. They found that patients with higher scores had better overall survival and progression-free survival compared with those with lower scores. Specifically, patients with better scores lived longer. The study concluded that these scores can help predict survival in these patients treated with nivolumab.

Long-Term Temporal Trends of Real-World Healthcare Costs Associated with Nivolumab Plus Ipilimumab and Pembrolizumab Plus Axitinib as First-Line Treatment for Advanced or Metastatic Renal Cell Carcinoma.

INTRODUCTION: Nivolumab plus ipilimumab (NIVO + IPI) and pembrolizumab plus axitinib (PEM + AXI) are first-line (1L) treatments for advanced or metastatic renal cell carcinoma (aRCC), although the long-term trends in their associated real-world healthcare costs are not well defined. We compared the real-world healthcare costs of patients with aRCC who received 1L NIVO + IPI or PEM + AXI over 24 months. METHODS: Adults with RCC and secondary malignancy who initiated 1L NIVO + IPI or PEM + AXI were identified in the Merative MarketScan Commercial and Medicare Supplemental Databases (01/01/2004 to 09/30/2021). All-cause and RCC-related healthcare costs (unadjusted and adjusted) were assessed per patient per month (PPPM) at 6-month intervals post-treatment initiation (index date) up to 24 months, and differences between the NIVO + IPI and PEM + AXI cohorts were compared. RESULTS: Of 325 patients with aRCC, 219 received NIVO + IPI and 106 received PEM + AXI as the 1L treatment. According to patients' follow-up length, the analyses for months 7-12 included 210 patients in the NIVO + IPI cohort and 103 in the PEM + AXI cohort; months 13-18 included 119 and 48 patients, respectively; and months 19-24 included 81 and 25 patients. PPPM unadjusted all-cause total costs were $46,348 for NIVO + IPI and $38,097 for PEM + AXI in months 1-6; $26,840 versus $27,983, respectively, in months 7-12; $22,899 versus $25,137 in months 13-18; and $22,279 versus $27,947 in months 19-24. PPPM unadjusted RCC-related costs were $44,059 for NIVO + IPI and $36,456 for PEM + AXI in months 1-6; $25,144 versus $26,692, respectively, in months 7-12; $21,645 versus $23,709 in months 13-18; and $20,486 versus $25,515 in months 19-24. PPPM costs declined more rapidly for patients receiving NIVO + IPI compared to those receiving PEM + AXI, resulting in significantly lower all-cause costs associated with NIVO + IPI during months 19-24 (difference - $10,914 [95% confidence interval - $21,436, - $1091]) and RCC-related costs during months 7-12 (- $4747 [(- $8929, - $512]) and 19-24 (- $10,261 [- $20,842, - $421]) after adjustment. Cost savings for NIVO + IPI versus PEM + AXI were driven by differences in drug costs which, after adjustment, were significantly lower in months 7-12 (difference - $5555 [all-cause], - $5689 [RCC-related]); 13-18 (- $7217 and - $6870, respectively); and 19-24 (- $16,682 and - $16,125). CONCLUSION: Although the real-world PPPM healthcare costs of 1L NIVO + IPI were higher compared with PEM + AXI in the first 6 months of treatment, the costs associated with NIVO + IPI rapidly declined thereafter, resulting in significantly lower costs vs. PEM + AXI from months 7 to 24.

The gut microbiome and dietary metabolites in the treatment of renal cell carcinoma.

The gut microbiome is interlinked with renal cell carcinoma (RCC) and its response to systemic treatment. Mounting data suggests that certain elements of the gut microbiome may correlate with improved outcomes. New generation sequencing techniques and advanced bioinformatic data curation are accelerating the investigation of specific markers and metabolites that could predict treatment response. A variety of new therapeutic strategies, such as fecal microbiota transplantation, probiotic supplements, and dietary interventions, are currently being developed to modify the gut microbiome and improve anticancer therapies in patients with RCC. This review discusses the preliminary evidence indicating the role of the microbiome in cancer treatment, the techniques and tools necessary for its proper study and some of the current forms with which the microbiome can be modulated to improve patient outcomes.

Long-term responders to nivolumab in previously treated advanced renal cell carcinoma: a sub-analysis of meet-URO15 study.

BACKGROUND: Although nivolumab prolongs overall survival (OS) in pretreated patients with metastatic renal cell carcinoma (mRCC), underlining clinical and biological features of long-term responses are still to be determined. This study aims to investigate clinical and pathological characteristics of mRCC patients who achieved long-term responses during nivolumab treatment. MATERIALS AND METHODS: A retrospective analysis was performed on mRCC patients receiving nivolumab as second or further therapy line between May 2016 and January 2019 in 34 Italian Oncology Centres. Outcome assessments and logistic regression were performed to evaluate factors influencing long-term responses. RESULTS: A total of 571 patients with a median age of 61 years (range 17-85) were included in the analysis. With a median follow-up of 22.1 (1.0-89.0) months, 23.1% of patients were 2-year progression-free on treatment with nivolumab, hence they were categorized as long-term responders. Baseline characteristics, including age, gender, and histology, were similar between long- and short-term responders. Karnofsky Performance Status ≥ 80% was significantly associated with long-term response (p = 0.02), while bone metastases (p = 0.03), International mRCC Database Consortium intermediate-poor risk (p < 0.01) and Neutrophil-to-Lymphocyte Ratio ≥ 3.2 (p = 0.02) were associate with short-term responses. Long-term responders exhibited a median progression-free survival of 55.0 months versus 4.0 months of the short-term responders. The median OS was not reached in long-term responders while it was 17.0 months for short*term responders. CONCLUSION: This retrospective analysis sheds light on factors associated with long-term response to nivolumab in mRCC. Understanding these clinical features will be essential for selecting patients who may mostly benefit from immunotherapy.

First-line therapy for metastatic renal cell carcinoma: A propensity score-matched comparison of efficacy and safety.

PURPOSE: Immune checkpoint inhibitor (ICI)-based combination therapy is a standard systemic treatment for metastatic renal cell carcinoma (mRCC). Although differential pharmacologic action between ICI+ICI and ICI+tyrosine kinase inhibitor (TKI) combinations may affect outcomes, comparative studies using real-world data are few. METHODS: We retrospectively analyzed the records of 447 mRCC patients treated with 1st-line ICI-based combinations at multiple institutions between January 2018 and August 2023, and selected 320 patients diagnosed with clear cell RCC (ccRCC) for further study. Cohorts were matched using one-to-one propensity scores based on IMDC risk classification. Overall survival (OS), progression-free survival (PFS), objective response rates (ORRs), and treatment-related adverse events (TrAE) were compared. RESULTS: The matching process yielded 228 metastatic ccRCC patients treated with ICI+ICI (n = 114) or ICI+TKI (n = 114). Median OS was 53 months (95%CI: 33-NA) in patients treated with ICI+ICI and was not reached (95%CI: 43-NA) with ICI+TKI (P = 0.24). Median PFS was significantly shorter for ICI+ICI (13 months, 95%CI: 7-25) than for ICI+TKI (25 months, 95%CI: 13-NA) (P = 0.047). There were no differences in second-line PFS for sequential therapy after 1st-line combinations of ICI+ICI or ICI+TKI (6 vs. 8 months, P = 0.6). There were no differences in ORR between the 2 groups (ICI+ICI: 51% vs. ICI+TKI: 55%, P = 0.8); the progressive disease (PD) rate was significantly higher in patients treated with the ICI+ICI combination (24% vs. 11%, P = 0.029). The rate of any grade TrAE was significantly higher in patients treated with ICI+TKI (71% vs. 85%, P = 0.016), but we found no differences in severe TrAE between the 2 groups (39% vs. 36%, P = 0.8). CONCLUSIONS: In a matched cohort of real-world data, we confirmed comparable OS benefits between ICI+ICI and ICI+TKI combinations. However, differential clinical behaviors in terms of PFS, PD rates, and TrAE between ICI-based combinations may enrich clinical decision-making.

TNFSF9 Is Associated with Favorable Tumor Immune Microenvironment in Patients with Renal Cell Carcinoma Who Are Treated with the Combination Therapy of Nivolumab and Ipilimumab.

Combination therapy of nivolumab and ipilimumab (NIVO + IPI) for metastatic renal cell carcinoma (mRCC) has shown efficacy, but approximately 20% of patients experience disease progression in the early stages of treatment. No useful biomarkers have been reported to date. Therefore, it is desirable to identify biomarkers to predict treatment responses in advance. We examined the tumor microenvironment (TME)-related gene expression in mRCC patients treated with NIVO + IPI, between the response and non-response groups, using tumor tissues, before administering NIVO + IPI. In TME-related genes, TNFSF9 expression was identified as a candidate for the predictive biomarker. Its expression discriminated between the response and non-response groups with 88.89% sensitivity and 87.50% specificity (AUC = 0.9444). We further analyzed the roles of TNFSF9 in TME using bioinformatics from The Cancer Genome Atlas (TCGA) cohort. An adaptive immune response was activated in the TNFSF9-high-expression tumors. Indeed, T follicular helper cells, plasma B cells, and tumor-infiltrating CD8+ T cells were increased in the tumors, which indicates the promotion of humoral immunity due to enhanced T-B interactions. However, as the number of regulatory T cells (Treg) increased in the tumors, the percentage of dysfunctional T cells also increased. This suggests that not only PD-1 but also CTLA-4 inhibition may have suppressed Treg activation and improved the therapeutic effect in the TNFSF9 high-expression tumors. Therefore, TNFSF9 may predict the therapeutic efficacy of NIVO + IPI for mRCC and allow more appropriate patient selection.

Right Atrial Mass and Severe Symptomatic Anemia as the Initial Presentation of Renal Cell Carcinoma.

We present a case of a 63-year-old male with a history significant for hypertension and a 45-pack-year smoking history who presented with severe symptomatic anemia. Rather quickly, upon imaging, he was found to have a 10 cm liver mass, a right renal mass, and a right atrial mass. A liver biopsy was performed and confirmed metastatic renal cell carcinoma (clear cell variant). Due to the extensive disease burden and patient preference, curative surgery was not pursued. This case highlights the rare but critical complications that can present as the initial presentation of renal cell carcinoma.

Prognostic value of systemic immune-inflammation index in patients with metastatic renal cell carcinoma treated with systemic therapy: a meta-analysis.

Objective: A novel systemic immune-inflammation index (SII), based on the neutrophils, lymphocytes, and platelet counts, is associated with the prognosis of several cancers, including non-metastatic renal cell carcinoma (RCC). In the present study, we evaluate the prognostic significance of SII in patients with metastatic RCC (mRCC) treated with systemic therapy. Method: Relevant studies were searched comprehensively from Web of Science, PubMed, Embase and the Cochrane Library up to January 2024. The pooled hazard ratio (HR) and 95% confidence interval (CI) were extracted from each study to evaluate the prognostic value of SII in patients with mRCC treated with tyrosine kinase inhibitor (TKI) or immune checkpoint inhibitor (ICI). Results: A total of 12 studies including 4,238 patients were included in the final analysis. High SII was significantly correlated to poor overall survival (OS, HR = 1.88; 95% CI 1.60-2.21; P < 0.001) and progression-free survival (PFS, HR = 1.66; 95% CI 1.39-1.99; P < 0.001). Stratified by therapy, high SII was also related to the poor OS (TKI: HR = 1.63, P < 0.001; ICI: HR = 2.27, P < 0.001) and PFS (TKI: HR = 1.67, P < 0.001; ICI: HR = 1.88, P = 0.002). Conclusion: In conclusion, high SII could serve as an unfavorable factor in patients with mRCC treated with systemic therapy. Stratified by therapies, the elevated SII was also associated with worse prognosis. Whereas, more prospective and large-scale studies are warranted to validate our findings. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42024522831, identifier CRD42024522831.

Design and Rationale of the Outcomes Database to Prospectively Assess the Changing Therapy Landscape in Renal Cell Carcinoma Registry: A Multi-institutional, Prospective Study of Patients with Metastatic Renal Cell Carcinoma.

Introduction and hypotheses: The Outcomes Database to prospectivelY aSSEss the changing TherapY landscape in Renal Cell Carcinoma (ODYSSEY RCC) Registry is a large, nationally representative prospective registry of patients with metastatic renal cell carcinoma (mRCC) that aims to provide a real-world picture of longitudinal clinical management and patient experiences that impact clinical outcomes. The primary goal of this study is to understand the cancer management and health-related quality of life in patients with mRCC in routine real-world clinical practice in the USA. Design: This is an observational, phase 4 study with planned enrollment of up to 800 patients aged ≥19 yr with mRCC in the USA. Patients will be identified through electronic health record (EHR) data from the PCORnet network of sites for care received at collaborating sites. A unique aspect of the study is the multiple data sources that will be linked to the EHR data. These include: (1) Medicare claims data, (2) laboratory results, (3) tissue specimens, (4) radiographic images, and (5) patient-reported outcomes, physicians' treatment selection, and discontinuation surveys. Protocol overview: We created a novel data resource that can inform patient care. Investigators have the opportunity to use these to study novel research questions after submitting an ancillary proposal and upon approval of the executive committee. Limitations include the potential for selection bias, residual confounding, and missing information. Summary: The ODYSSEY Registry will provide an advanced data resource that can examine numerous clinical questions related to patient and physician choice, and support methodological research related to omics and artificial intelligence. Patient summary: Cancer medications and treatments are changing rapidly. Collecting data on real-world clinical practice and patient-answered questionnaires will help us better understand cancer management and health-related quality of life while receiving metastatic renal cell carcinoma-specific treatment.

Real-world experience of second-line axitinib in metastatic renal cell carcinoma: analysis of the Swedish population.

Aim: Assess the time-to-treatment discontinuation (TTD) and overall survival (OS) in a Swedish metastatic renal cell carcinoma (mRCC) nationwide cohort who received second-line axitinib.Methods: Retrospective analysis of 110 patients with mRCC treated with second-line axitinib in Sweden (2012-2019). Patients included in the study received axitinib after mainly first-line sunitinib or pazopanib.Results: The median (95% CI) TTD of patients who received second-line axitinib was 5.2 (3.7-6.1) months with 6 (5.5%) patients still receiving treatment at the time of analysis. Median (95% CI) OS was 12.2 (7.7-14.2) months.Conclusion: The results are consistent with previous findings in mRCC and add to the evidence demonstrating efficacy of second-line axitinib, after failure of a prior anti-angiogenic therapy in a real-world setting.Clinical Trial Registration: NCT04669366 (ClinicalTrials.gov).

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International multicenter real-world REGistry for patients with metastatic renAL cell carcinoma - Meet-URO 33 study (REGAL study).

BACKGROUND: Nowadays, different therapeutic options are available for the first-line treatment of metastatic renal cell carcinoma (mRCC). Immuno-combinations are the standard first-line therapy in all mRCC patients regardless of the International Metastatic RCC Database Consortium (IMDC) risk category, even though TKI monotherapy is still a therapeutic option in selected patients. However, comparisons between the different first-line treatment strategies are lacking and few real-world data are available in this setting. For this reason, the regimen choice represents an important issue in clinical practice and the optimal treatment sequence remains unclear. METHODS: The REGAL study is a multicentric prospective observational study enrolling mRCC patients treated with first-line systemic therapy according to clinical practice in a real-world setting. A retrospective cohort of mRCC patients who received first-line systemic therapy from the 1st of January 2021 will also be included. The primary objective is to identify potential prognostic and predictive factors that could help guide the treatment choice; secondary objectives included the assessment of the prognostic performance of the novel prognostic Meet-URO score (IMDC score + neutrophil-to-lymphocyte ratio + bone metastases) compared with the IMDC score and the comparison between treatment strategies according to response and survival outcomes and toxicity profile. DISCUSSION: Considering the high number of therapeutic first-line strategies available for mRCC, the identification of clinical prognostic and predictive factors to candidate patients to a preferable systemic therapy is still an unmet clinical need. The Meet-URO 33 study aims to provide a large-scale real-world database on mRCC patients, to identify the clinical predictive and prognostic factors and the different performances between the ICI-based combinations according to response, survival and toxicity. TRIAL REGISTRATION: CESC IOV 2023-78.

First-Line Immune Combination Therapies for Nonclear Cell Versus Clear Cell Metastatic Renal Cell Carcinoma: Real-World Multicenter Data From Germany.

INTRODUCTION: The aim was to compare treatment outcomes of clear cell metastatic renal cell carcinoma (ccmRCC) versus non-ccmRCC (nccmRCC) patients who received first-line immune combination therapies. MATERIALS AND METHODS: Within our retrospective multi-institutional consecutive database of eight tertiary-care centers, we identified mRCC patients treated with first-line immune combination therapies between 11/2017 and 12/2022. Using log-rank analysis and multivariable Cox regression, we tested for differences in overall survival (OS) and progression-free survival (PFS) of nccmRCC versus ccmRCC patients. Covariables consisted of age at diagnosis, sex, International Metastatic Renal Cell Carcinoma Database Consortium risk groups, Eastern Cooperative Oncology Group status, and sarcomatoid feature. RESULTS: Of 289 study patients, 39 (13%) patients harbored nccmRCC. Median OS was 37 months versus not reached for ccmRCC versus nccmRCC patients (P = .6). Median PFS was 13 versus 15 months (P = .9). Multivariable Cox regression models did not identify nccmRCC as an independent predictor of higher overall mortality in mRCC patients (hazard ratio [HR]: 1.23; P = .6) or a higher progression rate (HR: 1.0; P = 1.0). CONCLUSION: In our real-world multi-institutional study, no differences in OS and PFS between ccmRCC and nccmRCC patients receiving first-line immune combination treatment were observed, even after adjustment for important patient and tumor characteristics. More prospective trials in nccmRCC patients are needed.