bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy of first-line combination therapy in metastatic renal cell carcinoma (mRCC) patients (pts) with poor performance status (PS).
Authors: Carril Lucia , Colomba Emeline , Romero-Ferreiro Carmen , Cerbone Luigi , Ratta Raffaele , Barthélémy Philippe , Vindry Clarisse , Cherifi Francois , Boughalem Elouen , Linassier Claude , Fornarini Giuseppe , Gross-Goupil Marine , Saldana Carolina , Martin Soberón Maria Cruz , de Velasco Guillermo , Pernaut Cristina , Alves Costa Silva Carolina , Flippot Ronan , Escudier Bernard , Albiges Laurence 
Published: February 2022

320 Background: Immune checkpoint combination therapy (ICI-combo) is the new standard of care for mRCC in first-line setting. However, pts with poor PS (≥2) were excluded from pivotal trials. Hence, the activity and safety of ICI-combo in this group of pts is still unknown. Methods: We performed a multicentre retrospective study of PS≥2 mRCC pts who received ICI-combo, either nivolumab-ipilimumab (NI) or pembrolizumab-axitinib (PA) as first-line treatment between 2017-2021. Patient’s characteristics, clinical outcomes and toxicity were retrospectively reviewed. We analysed overall response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS) and grade ≥3 treatment-related adverse events (G≥3 AEs) in pts treated with NI or PA. The association between LIPI (Lung Immune Prognostic Index) and ORR, PFS and OS was also evaluated. Results: We identified 56 mRCC pts with PS≥2 treated with ICI-combo across 13 institutions. Thirty-six and 20 pts were treated with NI and PA respectively. Median age at diagnosis was 64 (31-83) years, 38 (68%) were male, 16 (29%) had prior nephrectomy and 40 (71%) had synchronous metastatic disease at diagnosis. Respectively, 19 (34%) and 37 (66%) pts were intermediate and poor risk according to IMDC. Fifty pts (89%) were clear cell RCC, and only 4 pts had sarcomatoid features reported. At the time of analysis (median follow-up 11.1 months(mo)) 45% pts were dead. The ORR for the entire cohort was 27%; ORR was numerically higher with PA (42%) than with NI (20%) but did not reach statistical significancy (p=0.157). Median PFS (mPFS) and mOS in the entire cohort were 4.4 mo and 15.9 mo respectively. No significant differences in PFS, OS or the rate of G≥3AEs were seen between the NI and PA groups. Efficacy and toxicity outcomes are described in the table below. No significant differences in OS or PFS according to the IMDC risk score were observed (p=0.818). However, LIPI was significantly associated with OS (poor LIPI: HR=8.18; p=0.004) and PFS (Intermediate LIPI: HR=2.4; p=0.048 and poor LIPI: HR=8.59; p<0.001). LIPI was predictive of response in patients treated with NI (p=0.024). Conclusions: We report the first cohort of PS≥2 mRCC pts treated with ICI-combo in first-line setting. No significant differences in ORR, PFS or OS were seen between NI and PA. LIPI was significantly associated with both OS and PFS, and was predictive of ORR in the NI group. Prospective real-world studies are needed to confirm these results.[Table: see text]
Cost effectiveness of adjuvant pembrolizumab after nephrectomy for RCC: Insights for patient selection from a Markov model.
Authors: Sharma Vidit , Wymer Kevin M , Joyce Daniel D. , Moriarty James P. , Borah Bijan J , Thompson R. Houston , Costello Brian Addis , Leibovich Bradley C. , Boorjian Stephen A. 
Published: February 2022

321 Background: KEYNOTE-564 demonstrated that adjuvant pembrolizumab after nephrectomy for high-risk clear cell renal cell carcinoma (RCC) decreased the risk of disease progression and – albeit with immature follow-up (2 years) – found a signal of improved overall survival as well. Herein, we used extrapolations from a Markov-model, accounting for the costs and toxicities of pembrolizumab relative to its efficacy, to investigate its utility at a population level. Methods: A decision-analytic Markov Model was used to conduct a cost-utility analysis of adjuvant pembrolizumab versus placebo after nephrectomy for high risk RCC, using data from KEYNOTE-564 to inform model probabilities. Transition probabilities not found in KEYNOTE-564, in addition to utility values, were extracted from the literature. Base case analyses were conducted with 5-year and 15-year time horizons (using extrapolations from 2-year outcomes), and 3-week time cycles. Primary outcomes were Quality-adjusted life years (QALYs), 2021 US Medicare costs, and Incremental cost-effectiveness ratios (ICERs). The willingness-to-pay threshold was set at $100,000/QALY. One-way sensitivity analyses were used to identify cost-effectiveness thresholds of individual parameters while probabilistic sensitivity analyses with 100,000 Monte-Carlo simulations were used to simultaneously vary all model inputs. Results: Pembrolizumab was associated with higher QALYs and costs relative to placebo (Table). Pembrolizumab was not cost-effective at a 5-year time horizon but was cost-effective at 15 years and beyond. One-way sensitivity analysis noted that pembrolizumab became cost-effective at 5-years if: 1) its administration cost was less than $5,064 (base = $10,278) or 2) if the 5-year risk of progression was 18.8% higher in placebo vs pembrolizumab (base = 9%). Using pembrolizumab’s reported hazard ratio of 0.68 for progression from KEYNOTE-564, we estimated that pembrolizumab would be cost-effective at 5-years for all patients with a Mayo Progression Free Survival Score of 10 or higher. Probabilistic sensitivity analysis found that pembrolizumab was cost-effective for 29% and 58% of microsimulations at 5 and 15 years, respectively. Conclusions: At current prices, adjuvant pembrolizumab was not cost-effective for all trial patients at a population level at 5-years after treatment but may be cost-effective for time horizons over 15 years. Instead, adjuvant pembrolizumab was found to be cost-effective only for the highest risk subsets of RCC at 5-years. Longer term trial data of progression-free survival and overall survival are necessary to confirm these extrapolations.[Table: see text]
Does presence of diabetes mellitus impact patient oncological outcomes in renal cell carcinoma: A multicenter analysis.
Authors: Saidian Ava , Walia Arman , Patil Dattatraya , Saito Kazutaka , Patel Devin , Nguyen Mimi Vu , Chakoumakos Madison , Ghali Fady , Narasimhan Rekha S , Perry John M , Meagher Margaret , Yasuda Yosuke , Fujii Yasuhisa , Master Viraj A. 
Published: February 2022

325 Background: Diabetes mellitus (DM) has been hypothesized to be a risk factor for development of renal cell carcinoma (RCC). We evaluated impact of DM on survival outcomes in RCC. Methods: We performed a retrospective analysis of the International Marker Consortium for Renal Cancer (INMARC). The cohort was divided into three subgroups (patients with stage I vs. stage II vs. stage III RCC) for descriptive, survival and multivariable analysis of outcomes. Kaplan Meier Analysis (KMA) was used to compare diabetic and non-diabetic patients in the different stage subgroups to evaluate overall survival (OS), cancer-specific survival (CSS) and progression-free survival (PFS). Cox Regression multivariable analysis (MVA) was used to elucidate independent risk factors for all-cause mortality (ACM). Results: 2,927 patients with stage I RCC (709-DM/ 2218 non-DM), 2,513 with stage II RCC (688 DM/1825 non-DM) and 460 with stage 3 RCC (355 DM/ 105 non-DM) were analyzed. MVA revealed DMII having no impact on CSM (p=0.118) or PFS (p=0.316) across all stages. MVA for ACM revealed age (HR 1.026, p<0.001), male sex (HR=1.425, p<0.001), hypertension (HR=1.693, p <0.001) and tumor size (HR=1.064, p<0.001) as independent risk factors. KMA identified increased ACM in stage I (p<0.001) and stage III (p<0.001) RCC patients with non-DM compared to diabetic patients. Conclusions: Our findings suggest that DM may have impact on survival of in RCC, but this impact is mostly driven by non-oncologic, as opposed to oncologic effects. Further investigation is requisite.
The survival outcomes of the metastatic renal cell carcinoma with rhabdoid differentiation in immunotherapy era: Princess Margaret Cancer Center experience.
Authors: Al-Ezzi Esmail Mutahar , Mittal Abhenil , Wilson Brooke , Iafolla Marco , Spiliopoulou Pavlina , Sridhar Srikala S. , Fallah-Rad Nazanin , Chung Peter W. M. , Perlis Nathan , Hansen Aaron Richard 
Published: February 2022

333 Background: Patients (pts) diagnosed with metastatic renal cell carcinoma (mRCC) with rhabdoid differentiation (RD) have a poor prognosis due to aggressive tumor behavior and inherent treatment resistance to targeted therapies. However, recent data has demonstrated the survival benefit of immunotherapy (IO) in mRCC. Here, we report survival outcomes of pts with mRCC with RD treated with targeted therapy and or IO. Methods: This retrospective survival analysis was performed in pts with mRCC and RD treated with targeted treatment and IO at Princess Margaret Cancer Centre (PM), Toronto. Demographics, disease characteristics and survival outcomes were collected. Overall survival (OS) was calculated using the Kaplan-Meier method (log-rank). OS hazard ratio (HR) were calculated using cox proportional hazards model. IBM SPSS Statistics v26 was used to conduct statistical analyses. Results: We identified 474 pts diagnosed with mRCC at PM between 2002 and 2019. A total of 57 (12%) pts diagnosed with mRCC had RD and were treated with targeted and or IO agents. Of these, 42 (73.7%) pts had pure RD and 15 (26.3%) pts had mixed RD and sarcomatoid features. Median age was 62 yrs (35-86yrs) and 42 (73.7%) were male. Overall, as per the IMDC score, 5(8.8%), 27(47.4%) and 25(43.8%) pts were categorized as good, intermediate, and poor risk, respectively. In total, 34 (59.6%) pts were treated with targeted therapy only during their first and second line treatment course and 23 (40.4%) pts received IO alone or in combination with targeted treatment in the first or second line. With a median follow up of 53.4 months (range, 38.3-68.4 months), the median OS for the whole mRCC with RD cohort was 23.1 months (95% CI: 14.6-31.5). The median OS in all pts treated with targeted therapy only vs IO receipt was 13.1 months (95%CI: 5.4-20.8 months) vs not reached; p = 0.026, respectively. HR for OS was 0.44 (95%CI: 0.22-0.93; p = 0.03) favoring IO receipt. Conclusions: While the number of pts included in our retrospective review was small, our analysis has suggested that pts with mRCC and RD have poor survival outcomes that may be improved with IO treatment. RD is a histopathological feature that could identify pts who may benefit from IO therapy. Further analysis is needed to explore the impact of RD on IO treatment response.
Network meta-analysis (NMA) of second-line (2L) treatment options in metastatic renal cell carcinoma.
Authors: Recio-Boiles Alejandro , Obeng-Kusi Mavis , Choi Briana , Abraham Ivo 
Published: February 2022

337 Background: Immune checkpoint inhibitors, in combination either with a cytotoxic T-lymphocyte-associated protein 4 or tyrosine kinase inhibitor are approved for first-line (1L) therapy of metastatic renal cell carcinoma (mRCC). Of those, several have been shown to improve median progression-free survival (mPFS) in the 2L. A recent NMA by Irbaz et al. (PMID 33824031) identified the most effective 1L treatments for mRCC. In the absence of head-to-head randomized clinical trials (RCT), we performed an indirect comparison of 2L treatments for mRCC. Methods: We conducted literature searches in Medline, Embase, Cochrane Library, and Google Scholar to identify RCTs evaluating 2L treatments in mRCC. We extracted the mPFS hazard ratios (HR) and 95% confidence intervals (CI). We used a normal likelihood model that incorporates log HRs of the treatment differences for conducting the NMA. P-scores, measuring the certainty that one treatment is better than another averaged over all competing treatments, were used to rank treatments. Higher p scores indicate better outcomes. Data were analyzed with R netmeta package v.1.5-0. Results: All 8 therapies included in this analysis showed benefits in mPFS over placebo (Table). The combination of lenvatinib+everolimus had the lowest hazard of disease progression or death and pazopanib was the highest compared to placebo. Lenvatinib+everolimus ranked highest with a p-score of 0.96 followed by cabozantinib (0.88), and lenvatinib (0.79); with others having p-scores of 0.60 or less (placebo p-score 0.00). Conclusions: This NMA revealed that lenvatinib+everolimus and cabozantinib are most likely to produce the highest PFS benefit in 2L in mRCC. Future studies are needed to evaluate 1L and 2L sequencing options to further inform clinical practice. [Table: see text]
Efficacy and safety of nivolumab in renal cell carcinoma patients with BONE metastases: Results of the GETUG: AFU 26 nivoren multicenter phase II study.
Authors: Velev Maud , Dalban Cécile , Chevreau Christine , Gravis Gwenaelle , Negrier Sylvie , Laguerre Brigitte , Gross-Goupil Marine , Ladoire Sylvain , Ferrari Victoria , Geoffrois Lionnel , Curcio Hubert , Priou Frank , Thomas Quentin Dominique , Mione Cécile , Barthélémy Philippe , Tantot Florence , Escudier Bernard , Chabaud Sylvie , Albiges Laurence , Thibault Constance 
Published: February 2022

342 Background: Bone metastases (BM) in renal cell carcinoma (RCC) are associated with a poor prognosis based on retrospective studies in which patients were treated with antiangiogenic agents. Since the development of immune checkpoint inhibitors, few data are available regarding the prognosis impact of BM or the efficacy and safety of checkpoint inhibitors in patients with bones metastatic RCC. GETUG-AFU26-NIVOREN (NIVOREN) is a French multicenter prospective study in which patients were treated with nivolumab after failure of one or more antiangiogenic tyrosine kinase inhibitors. We therefore aim to evaluate the impact of BM on prognosis, and the efficacy and safety of nivolumab in patients with BM enrolled in NIVOREN trial. Methods: All adult patients with BM at inclusion were included in our study. The primary endpoint of this ancillary study was overall survival (OS). Secondary endpoints were progression-free survival (PFS), objective response rate (ORR), safety, and skeletal-related events (SRE) in patients with BM. Clinical data were collected prospectively, except for SRE data which were collected retrospectively in a complementary consent report form. Results: Among 720 patients treated with nivolumab in the NIVOREN study, 194 had BM at inclusion. After a median follow-up of 23.9 months, the median OS was 17.9 months in patients with BM versus 26.1 months in patients without BM (HR = 1.42 CI95% [1.13-1.79], p = 0.0023). After adjustment on sex, age, IMDC group and line of treatments, the difference was not significant (HR = 1.24, CI95% [0.98-1.56], p = 0.0707). The median PFS was shorter in patients with BM even after adjustment (2.8 versus 4.6 months, HR = 1.30 CI95% [1.08-1.56]), as well as the ORR (14.8% versus 23.3%). The safety profile was similar between patients with or without BM at inclusion. The incidence of SRE in the BM population was 36% during the treatment period with nivolumab. A post-hoc analysis evaluating the impact of bone-targeting agents in association with nivolumab on SRE incidence was performed. There was a statistically significant benefit in patients treated with bone-targeting agents on the incidence of SRE (OR = 0.367, CI95% [0.151-0.895], p = 0.0276). Conclusions: Nivolumab is associated with shorter OS, PFS, and lower ORR in patients with BM. Our study confirms, in the era of immunotherapy that patients with BM are associated with poorer prognosis and suggests that association with bone-targeting agents decreases the incidence of SRE. Clinical trial information: 2015-004117-24.
The role of cytoreductive nephrectomy and systemic therapy in the management of tumor thrombus in patients with metastatic renal cell carcinoma.
Authors: Mittal Abhenil , Al-Ezzi Esmail Mutahar , Li Xuan , Wilson Brooke , Spiliopoulou Pavlina , Sridhar Srikala S. , Fallah-Rad Nazanin , Chung Peter W. M. , Hamilton Robert James , Hansen Aaron Richard 
Published: February 2022

345 Background: Patients (pts) with metastatic renal cell carcinoma (mRCC) and tumor thrombus have historically been treated with cytoreductive nephrectomy (CN), however, their outcomes remain poor. Recent phase III data suggest the role for cytoreductive nephrectomy (CN) in mRCC is limited. To date, only case-reports have described thrombus response to systemic therapy. Here, we describe response and survival outcomes of de novo mRCC patients with thrombi treated with systemic therapy with or without CN. Methods: Pts with de novo mRCC at the Princess Margaret Cancer Centre were identified. Demographics, disease characteristics (including the presence of thrombus) and survival outcomes were collected. Progression free survival (PFS) and overall survival (OS) in months (m) was calculated using the Kaplan-Meier method (log-rank). Results: We identified 226 pts with de novo mRCC between 2002 and 2019. Pt demographics are listed in the table. In total, 157 pts underwent a CN and 69 received only systemic therapy. Of the total cohort, 64 pts (28%) had tumor thrombus at presentation (46 CN, 18 no CN). Of the 18 patients with tumor thrombus treated with only systemic therapy, 17 received first-line angiogenesis inhibitors and 1 had chemotherapy (medullary histology). Six (33%) had thrombus progression, 8 (44%) had stable disease and four (22%) had an objective response. Median PFS and OS for patients with and without tumor thrombus treated with systemic therapy only was not significantly different [5.3m (95% CI 3.6-11.7) vs 4.1m (95% CI 3.1-5.9)), p=0.33; OS: 12.1m (95% CI 8.8-27.7) vs 13.9m (95% CI 7.9-21.5), p=0.87). PFS for patients with tumor thrombus who had CN was similar to those treated with systemic therapy alone [8.4m (95% CI: 5.7-13.4) vs 5.3m (95% CI 3.6-11.7), p=0.57] but OS was significantly better favoring CN [29.4m (95% CI: 17.4-48.9) vs 12.1m (95% CI 8.8-27.7), p=0.01). Conclusions: In this largest series of patients with mRCC and thrombus treated with systemic therapy +/- CN, CN appears to plays an important role. More data is needed for patients with tumor thrombus treated with immunotherapy to confirm these findings and elucidate the role of surgery in those cohorts. Bias due to the retrospective study design is an important limitation.[Table: see text]
Efficacy of tyrosine kinase inhibitors (TKI) after combination ipilimumab plus nivolumab (I/N) in metastatic clear cell renal cell carcinoma (ccmRCC) patients: Results from the Canadian Kidney Cancer Information System (CKCis).
Authors: Kalirai Austin , Joy Isaiah , Ghosh Sunita , Kollmannsberger Christian K. , Hansen Aaron Richard , Thana Myuran , Graham Jeffrey , Heng Daniel Yick Chin , Castonguay Vincent , Bjarnason Georg A. , Breau Rodney H. , Kapoor Anil , Pouliot Frederic , Wood Lori , Basappa Naveen S. 
Published: February 2022

346 Background: The use of I/N is a proven first-line option for patients with intermediate/poor IMDC prognostic criteria. The use of vascular endothelial growth factor inhibitors such as sunitinib have shown activity in the treatment of ccmRCC, but their effectiveness post I/N needs better characterization. This study aims to demonstrate the efficacy of sunitinib, and other TKI agents post I/N in ccmRCC in a real world setting. Methods: Patients with ccmRCC who had received I/N and were subsequently treated with TKI between Jan 1, 2011 and December 31, 2019 were identified from CKCis. Time to treatment failure (TTF – time from start of first subsequent TKI to discontinuation for any reason) and overall survival (OS) – time from first subsequent TKI to death) were calculated using the Kaplan-Meier method. Cox regression was performed to adjust for IMDC criteria. RECIST criteria was used to determine best overall response (ORR) of TKI radiographically. Results: 64 patients were treated with TKI post I/N. Characteristics and outcomes are listed in the table. Of the second-line TKI patients, 51 received sunitinib, 10 received pazopanib and 3 received other TKI. Reasons for second-line TKI discontinuation are: 28% toxicity, 34% progression, 7% other reasons while 31% remain on treatment. Median follow-up time was 12.9m. ORR for second-line TKI overall and second-line sunitinib was 30.0% and 29.4%, respectively. Conclusions: These data show that TKI are active after I/N in ccmRCC. TTF may underestimate PFS due to the large number of patients discontinuing treatment for toxicity and not progression. Efficacy of second-line TKI post I/N in this dataset is similar that of first-line sunitinib from recent randomized phase III trials, suggesting that there may be no significant loss of TKI activity after having received first-line I/N. Overall, these data support the use of TKI after I/N.[Table: see text]
Association of adrenal metastases with outcomes in patients with metastatic clear cell renal cell carcinoma (mccRCC) treated with nivolumab in the GETUG-AFU-26 NIVOREN phase II trial.
Authors: Billon Emilien , Dalban Cécile , Oudard Stephane , Chevreau Christine , Laguerre Brigitte , Barthélémy Philippe , Borchiellini Delphine , Geoffrois Lionnel , Negrier Sylvie , Joly Florence , Thiery-Vuillemin Antoine , Gross-Goupil Marine , Rolland Frederic , Priou Frank , Mahammedi Hakim , Tantot Florence , Escudier Bernard , Chabaud Sylvie , Albiges Laurence , Gravis Gwenaelle 
Published: February 2022

348 Background: Glandular metastases (GMs) (adrenal, pancreas, thyroid, ovary, breast, or prostate) are rare in mccRCC. Several studies have observed significantly longer overall survival (OS) for GM patients treated with anti-angiogenic therapy. This study assesses outcomes from mccRCC treated with nivolumab with or without GMs. Methods: The GETUG-AFU 26 NIVOREN, phase II trial assessed the activity and safety of nivolumab in pts with mccRCC who failed antiangiogenic therapies (NCT03013335). Pts were stratified in two subgroups according to the presence of at least one GM. Specific analyzes were performed for pancreatic and adrenal metastases. Primary endpoint was OS, secondary endpoint were progression free survival (PFS) and overall response rate (ORR). Results: Between February 2016 and July 2017, among 720 patients treated by nivolumab 217 patients had GM (151: adrenal and 86: pancreatic metastases). Clinical characteristics were comparable between the two subgroups except for IMDC poor subgroup (19% vs 28%) and for Furhman grade IV (13.5% vs 23.4%) for GM and non GM respectively. Median time between metastatic disease and nivolumab was 3.2 years (y) vs 2 y for GM and non GM respectively and 2.8 vs 2.1 y with or without adrenal metastasis. There was no statistical difference in outcomes between pts with or without GMs. However, pts with adrenal metastases had worse OS (12-months survival: 64% vs 71.1%; HR 1.51 (1.19-1.92)); shorter PFS (6-months survival: 27.2% vs 36.6%; HR 1.29 (1.07-1.57)) and lower ORR (12.5% [7.6%; 19.0%] vs 23.2% [19.8%; 27.0%]; p = 0.005) than non-adrenal metastases. Conversely, patients with pancreatic metastases had significantly longer overall survival (12-months survival: 82.3% vs 67.9%; HR 0.59 (0.40-0.85)) in univariate analysis compared to non-pancreatic metastases. In multivariate analysis, only adrenal metastasis remained associated with dismal prognosis (Table). Conclusions: Adrenal metastasis is an independent poor prognostic factor for response and survival in the GETUG-AFU 26 NIVOREN phase II trial. Limited activity with nivolumab is observed for patients with adrenal metastases from mccRCC without difference with previous anti angiogenic therapy. Molecular characterization could help to identify the angiogenic profile of adrenal metastases. Clinical trial information: NCT03013335. [Table: see text]