bluuebunny/crossref_metadata_2025_split huggingface dataset:
Acute interstitial nephritis (AIN) following immune checkpoint inhibitor (ICI) therapy in metastatic RCC (mRCC) as a potential predictor of response.
Authors: Patel Viral M. , Elias Roy , Formella Joseph , Schwartzman William , Christie Alana , Hammers Hans J. , Brugarolas James 
Published: February 2020

674 Background: ICIs such as nivolumab (N) have improved outcomes in mRCC patients (pts), but are also associated with immune-related adverse events. As has been shown in melanoma, we hypothesized that pts experiencing an autoimmune reaction directed against the tissue of origin may be more likely to benefit from ICI. Specifically, we evaluated whether pts with nivolumab-induced AIN (N-AIN) exhibited improved outcomes. Methods: We identified all patients with mRCC at UT Southwestern Medical Center from 2014 - 2018 who received at least one dose of N. We extracted creatinine (Cr) values over the entirety of each pt's N treatment course from the electronic medical record. Pts with a 1.5 fold Cr increase over baseline were investigated. The diagnosis of N-AIN was made by biopsy or by clinical criteria (timing of kidney injury, laboratory analysis, and exclusion of other causes). Results: We identified 177 mRCC pts who received at least one dose of N, 36 of whom had at least a 1.5 fold increase in Cr over baseline while on treatment. Of those, two had biopsy-proven AIN and one was clinically diagnosed, resulting in an incidence of 1.7%. Two received N monotherapy after first line, and the third in combination with ipilimumab as initial therapy. The earliest case of N-AIN occurred 1.5 months from N onset, and the others were diagnosed at 11 and 12 months. Of the 3 pts, one had a partial response lasting 2 years, and the other two had a complete response which is ongoing in both pts with over 2 years of follow up. In all 3 cases, N-AIN was treated with cessation of N and prednisone with a return to baseline kidney function. None required dialysis. Conclusions: AIN is a rare event with N, but it may portend a higher likelihood of response. One possible explanation is antigenic crossover between normal renal tubular cells and mRCC, resulting in a robust immune response.
Pegilodecakin as monotherapy or in combination with anti-PD-1 or tyrosine kinase inhibitor in heavily pretreated patients with advanced renal cell carcinoma (RCC): Updated results from phase I/Ib IVY study.
Authors: Naing Aung , Papadopoulos Kyriakos P. , Wong Deborah J.L. , Aljumaily Raid , Hung Annie , Afable Manuel , Kim Jong Seok , Ferry David , Drakaki Alexandra , Bendell Johanna C. , Tannir Nizar M. 
Published: February 2020

679 Background: Pegilodecakin (PEG), a pegylated recombinant human interleukin-10, has demonstrated clinical benefit and manageable toxicity in advanced RCC (Naing et al. 2016 JCO, Naing et al. 2019 Lancet Oncol). As part of the multi-arm (arm A to J) phase 1 IVY study, PEG alone (Part A) or in combination with pazopanib (Part G) or anti-PD-1 (pembrolizumab or nivolumab; Parts H+I) were investigated in heavily pretreated RCC patients (pts). Methods: In a phase 1/1b study which enrolled 353 pts in the US from 2013 to 2017, we analyzed treatment-related adverse events (TRAEs) graded by CTCAE v 4.02, tumor response by irRC, progression-free survival (PFS), and overall survival (OS) for all the advanced RCC pts who received PEG-containing treatment (n=66). Data cut-off was February 19, 2019. Results: Sixty six heavily pretreated RCC pts received PEG alone (n=24, 1-20 µg/kg), with pazopanib (n=4, 10µg/kg), with pembrolizumab (n=9, 10-20 µg/kg), or with nivolumab (n=29, 10-20 µg/kg). Most pts were male (70%), median age 62.5 years, initially diagnosed as stage IV (42%) with clear cell histology (64%), ECOG performance status of 1 (58%), and intermediate/poor (73%/14%) risk per IMDC category. Patients received a median number of 2 prior therapies. Most common grade 3/4 TRAEs were anemia (32%), thrombocytopenia (15%), and hypertriglyceridemia (14%). No pts died due to a TRAE. Median follow-up was 31.5 months. Conclusions: PEG alone or in combination with anti-PD-1 or pazopanib suggested some clinical activity with manageable toxicity in advanced RCC pts. These findings support further ongoing studies of PEG combinations in RCC pts. Clinical trial information: NCT02009449 .[Table: see text]
Epidemiology and regional variation in the mortality of patients admitted with prostate cancer in the United States.
Authors: Mariam Roy Arya , Konda Manojna , Goel Akshay , Verma Rashmi 
Published: February 2020

69 Background: Prostate cancer is one of the most common cancers in men and one of the leading causes of death among men of all races worldwide. Prostate cancer prevalence and mortality vary substantially by race, ethnicity and geography. The reason behind the disparity is unclear, however, access to screening and treatment, variation in exposure to risk factors, genetic susceptibility, lifestyle practices are the suggested factors that affect the disparity. Methods: We conducted a retrospective analysis of the National Inpatient Sample Database for the year 2016. Patients who were admitted with a principal diagnosis of Malignant Neoplasm of Prostate (MNP) were identified using ICD-10 codes. The epidemiology, racial disparities and regional variations in the mortality of prostate cancer, trend in the cost and length of stay were studied. Results: A total of 39,853 hospitalizations were identified with a principal diagnosis of MNP. The prevalence of MNP was found to be 0.56% with mean age of diagnosis 71.36 ± 0.55. The prevalence of prostate cancer was found to be highest in African Americans (0.65%), followed by Caucasians (0.60%). The disease-specific mortality rate for MNP was 3.45% (n=1,375). African Americans (AA) had 32% more risk of dying with prostate cancer when compared to all the other groups (OR= 1.322, P= 0.001, 95% CI= 1.14-1.52). Caucasians had 25% less chance of dying and Hispanic had 28% less chance of dying with prostate cancer when compared to AA (OR= 0.755, P= 0.001, CI= 0.65-0.87 vs OR= 0.72, P= 0.016, CI= 0.56- 0.94). Those who admitted to West were 22% more likely to die and those admitted to Northeast were 18% more likely to die when compared to Midwest and south regions (OR= 1.22, P= 0.037, CI= 1.01- 1.47 vs OR= 1.18, P= 0.062, CI= 0.91-1.4). The length of stay and also cost of stay were found to be highest for African American population. Conclusions: The prevalence, mortality of prostate cancer, cost and length of inpatient stay were highest among African Americans. There was a statistically significant difference in the mortality rate of prostate cancer based on the hospital regions in the United States. More studies are needed to better understand the reasons behind the regional difference.
Clinical outcomes of metastatic renal carcinoma following disease progression to programmed death (PD)-1 or PD-L1 inhibitors (I-O): A Meet-URO group real-world study (Meet-Uro 7).
Authors: Santini Daniele , Stellato Marco , De Giorgi Ugo , Pignata Sandro , Pantano Francesco , De Lisi Delia , Casadei Chiara , Maruzzo Marco , Naglieri Emanuele , Buti Sebastiano , De Vivo Rocco , Di Lorenzo Giuseppe , Sbrana Andrea , Soraru' Mariella , Fornarini Giuseppe , Mucciarini Claudia , Grillone Francesco , Roviello Giandomenico , Vignani Francesca , Procopio Giuseppe 
Published: February 2020

691 Background: In metastatic renal cell carcinoma (mRCC), immune-oncology (IO), alone or in combination, (IO-IO or IO-TKI) has changed the therapeutic scenario. Few real-world data are available about safety and outcome after IO progression. Methods: Baseline characteristics, outcome data including progression-free survival (PFS) and toxicities were retrospectively collected from 162 eligible pts treated in 16 Italian referral centers adhering to the Meet-Uro group and progressing to IO. Results: 111 pts (68,5%) were treated after progression to IO. 142 (87.6%) pts received IO as second line, 5 pts as first line and 16 pts as further line. Subsequent therapy included cabozantinib (n = 79, 48.0%), everolimus (n = 11, 6.7%), sunitinib (n = 6, 3.7%) and others (n = 15, 9.25%). Median IO-PFS was 4 months (95%CI 3.1-4.8) with no difference in pts pretreated with pazopanib or sunitinib (4 months (95%CI 2.4-5.5) vs 3,9 months (95%CI 2.9-4.9) p = 0.5). PFS tends to be longer in pts reporting adverse events of any grade (5.03 (95%CI 3.8-6.1) vs 2,99 (95%CI 2.4-3.5) months p = 0.004) or without nephrectomy (4.1 vs 2.9 months p = 0.071). Median PFS, in pts treated post-IO, was 6.5 months (95%CI 5.1-7.8). In term of best response, 55 pts (49%) had stability of disease/partial response and 29 pts (26%) had progressive disease, for the other pts treatment is still ongoing. Pts with ECOG PS 0 at progression to IO, had longer PFS, 11 months (95%CI 5.7-17.5) as well as those treated with cabozantinib (7.6 months, 95%CI 5.2-10.1) compared to everolimus, (3.2 months, 95%CI 1.8-4.5) or other drugs (4.3 months, 95%CI 1.3-7.4) p = 0.001. All grade adverse events were reported in 83 pts (74%) with G3-G4 adverse events in 39 pts (35%). Median overall survival, from first line, was 41,1 months (95%CI 30.4-51.8). Conclusions: In our real world experience after progression to IO, most pts received VEGF-TKI and mTOR inhibitors that showed to be active and safe choices. Cabozantinib was associated with a longer mPFS.
Occurrence of tyrosine kinase inhibitors-induced renal impairment and its predictive value for the prognosis of patients with metastatic renal cell carcinoma.
Authors: Zhang Haoran , Zhang Xingming , Zhu Xudong , Zeng Hao , Li Zi , Shen Pengfei 
Published: February 2020

693 Background: To investigate the tyrosine kinase inhibitors (TKIs) related renal impairment (RI) on the therapy efficacy and survival of patients with metastatic renal cell carcinoma (mRCC). Methods: Clinical and pathological parameters of patients with mRCC treated with TKIs were retrospectively reviewed. Blood urea nitrogen (BUN), proteinuria(PU) and estimated glomerular filtration rate (eGFR) were defined as main renal function related parameters, and their levels at the time of pre- and post- TKIs treatment were recorded and analyzed. Abnormal BUN, PU and/or eGFR were defined as RI. Primary and secondary treatment outcomes were progression-free survival (PFS) and overall survival (OS), and tumor response was defined as secondary treatment outcome. SPSS 24.0 and GraphPad Prism 7.0a were used for statistical analyses. Results: A total of 110 patients were included in this study. At baseline, patients with abnormal BUN, abnormal eGFR and PU were 25 (22.7%), 27 (25.5%) and 30 (27.3%), respectively, which increased to 46 (41.8%), 55 (50.0%) and 64(58.2%) after TKI treatment. Survival analysis showed that baseline RI had no impact either on prognosis, or the effectiveness of TKIs. On the contrary, for post-treatment RI, PU level, elevated PU, and eGFR level were independently related to PFS and OS. Besides, eGFR decrease >10% was indicated for longer OS time (19.0 vs 41.0 months, p=0.034). Sub-analysis suggested that, among 51 patients without RI pre-TKI therapy, eGFR level (P=0.004), eGFR decrease > 10% (P=0.012), PU level (P=0.014) as well as elevated PU level (P=0.006) were statistically correlated with OS time. However, the similar trend was not identified in those with baseline RI. Furthermore, baseline eGFR level (P=0.020) and eGFR decrease > 10% (P=0.016) within 1y after TKI therapy were identified to be effective biomarkers predicting OS. Conclusions: The occurrence of TKI-induced RI was indicated for better tumor response and survival outcomes, and provide valuable information for the individual treatment of mRCC patients. Thus, routinely monitoring of renal function, especially eGFR and PU, was highly recommended in TKIs-treated mRCC patients.
Safety and efficacy of retreatment with immune checkpoint inhibitors (ICIs) in patients with metastatic RCC (mRCC) who have previously received an ICI.
Authors: Ravi Praful , Bakouny Ziad , Flippot Ronan , Braun David A. , Abou Alaiwi Sarah , Wei Xiao X. , McGregor Bradley Alexander , Kilbridge Kerry L. , Choudhury Atish Dipankar , Harshman Lauren Christine , Choueiri Toni K. 
Published: February 2020

698 Background: Several ICIs are approved for use in first and subsequent lines of therapy in mRCC, either alone or in combination with another ICI or targeted therapy. There is limited data on whether patients who receive an ICI derive benefit from a subsequent line of ICI-based therapy. Methods: We reviewed mRCC patients at our institution who were treated with an ICI between 2009 and 2018 having previously received ICI-based therapy. The primary outcomes of interest were radiologic response and time to treatment failure (TTF) on ICI retreatment. Immune-related adverse events (irAEs) were graded using CTCAE v5.0. Results: A total of 31 patients were retreated with an ICI, either alone (n=15) or in combination with another ICI (n=8), tyrosine kinase inhibitor (n=2) or investigational agent (n=6); reasons for discontinuation of prior ICI were disease progression (n=23), toxicity (n=7) and study completion (n=1). Median age at the start of first-line therapy was 62 years and the majority of patients (n=30, 90%) had International Metastatic RCC Database Consortium intermediate- or poor-risk disease; median follow-up was 3.4 years (95% CI 2.5-4.6). The median number of lines of therapy received prior to ICI retreatment was 3 (range 1-7). Of 27 evaluable patients, 3 (11%) had a partial response (PR) to ICI retreatment (2 with ICI-ICI combination therapy and 1 with single-agent ICI), 13 (48%) had stable disease, and 11 (41%) had progressive disease (PD) as their best response; of the 3 with a PR, 2 had a PR and 1 had SD to prior ICI therapy. In comparison, 13 of 31 patients (42%) had a PR or better to first ICI-based therapy, with 4 (13%) having PD. Median TTF on ICI retreatment was 3.2 months (95% CI 1.8-5.2), compared to 8.2 months (3.3-10.0) on prior ICI. 19 patients experienced an irAE with ICI retreatment, with 8 (26%) suffering a grade 3 or higher irAE. Conclusions: Retreatment with ICIs after prior therapy with an ICI was relatively safe but demonstrated limited efficacy. Additional data, ideally from prospective studies, assessing outcomes of retreating patients with ICIs are needed to determine whether using different ICIs in sequence has a role in treatment of mRCC.
Optimal sequence strategy with nivolumab and targeted therapy in patients with metastatic renal cell carcinoma (mRCC).
Authors: Logeart Juliette , Simonaggio Audrey , Elaidi Reza Thierry , Hans Sophie , Thibault Constance , Oudard Stephane , Vano Yann-Alexandre 
Published: February 2020

700 Background: Nivolumab is an approved standard tretatment for pts with mRCC after one VEGFR-TKI failure. Some reports suggest that Nibolumab provides similar response rate across treatment line. Nevetheless, no comparative data has been reported on the sequence of 2nd line Nivolumab followed by TKI vs TKI followed by Nivolumab in 3rd or later line. Objective: To determine the optimal sequence of Nivolumab monotherapy and anti-VEGFR-TKI in mRCC beginning from the 2nd line. Methods: We included in a French expert center all patients with mRCC who received real-life experienced of anti-PD1 nivolumab monotherapy in 2nd line setting or later were included in a French expert center. Clinical characteristics were prospectively recorded including IDMC prognostic factors. Patients who did not receive TKI on the 1st line were excluded. Survival outcomes and subgroups analysis were performed using log rank test and univariate cox regression analysis. Results: 91 patients with mRCC received Nivolumab between January 2006 and May 2018, 58 pts received nivolumab in 2nde line (63%) and 33 in 3rd line and more. Median follow-up was 18.9 [0.1;143] months starting from the beginning of the 2nd line. All received first line anti-VEGFR TKI, 83%/11% sunitinib/pazopanib. At the beginning of 2nd line, IMDC prognostic groups were Fav 19%/Int 56%/ Poor 24%, with similar repartition (p=0,8) between pts treated with Nivolumab vs others. PFS at 6 months for 2nd line was in favor of patients treated by targeted treatments with respectively 63% (IC95% [46%;80%]) and 34% (IC95% [23%;49%]), p=0,06. OS at 24 months for 2nd line was significatively higher for patients treated by targeted treatments with 72% (IC95% [56;87%]) and 46% (IC95% [31%;61%]), p=0,007. Conclusions: We report for the first time the optimal timing to sequence Nivolumab – targeted therapy in patients with mRCC. We found better PFS and OS when Nivolumab is given after the 2nde line of treatment. Subgroups analysis including IMDC prognostic groups and duration of fist line TKI will be presented at the meeting.
Differences in the exposure to sunitinib in the immediate and deferred cytoreductive nephrectomy (CN) arms of the randomized controlled trial SURTIME.
Authors: Abu-Ghanem Yasmin , Van Thienen Johannes V. , Blank Christian U. , Powles Thomas , TOMBAL Bertrand F. , Collette Laurence , Haanen John B. A. G. , Bex Axel 
Published: February 2020

703 Background: SURTIME compared immediate CN followed by sunitinib 50mg/day (4/2 weeks on-off) 4 weeks after surgery (n=50) versus 3 cycles sunitinib followed by CN in the absence of progression and continued sunitinib 4 weeks after surgery (n=49). In the intention to treat analysis, the hazard ratio of the secondary endpoint overall survival (OS) favored deferred CN [0.57 (CI: 0.34–0.95, p=0.032)] with a median OS of 32.4 (CI: 14.5-65.3) versus only 15.0 months (CI: 9.3–29.5), following immediate CN. We investigated differences in exposure to systemic therapy between the two arms. Methods: Post-hoc exploratory analysis of number of patients receiving sunitinib, overall response rate (ORR) by RECIST 1.1, length of drug exposure and dose intensity in the immediate and deferred arm. Descriptive methods and 95% confidence intervals (CI) were used. Results: In the deferred arm, 97.7% (CI: 89.3-99.6; n=48) received sunitinib versus only 80% (CI: 66.9-88.7, n=40) in the immediate arm. Following immediate CN, 19.6% had confirmed progression at an interval CT scan 4 weeks after CN compared to baseline and 25% started with sunitinib > 4 weeks after surgery. At week 16, 46.0% had progressed at metastatic sites in the immediate CN arm versus 32.7% in the deferred arm, who had a per-protocol recommendation against nephrectomy. In the deferred arm, 83% completed 3 cycles sunitinib with 77.1% at >90%-120% relative dose intensity and an ORR of 29%, reducing the median sum of target lesions from 162 to 127 mm prior to planned CN.Of the patients who started with sunitinib in the immediate (n=40) or continued in the deferred arm after CN (n=29) median duration of treatment was 140 versus 351 days. Conclusions: With immediate CN fewer patients receive systemic therapy, which is administered later and shorter compared to the deferred approach. Starting systemic therapy with sunitinib leads to early and more profound control of the disease and identification of progression prior to planned CN which may translate into the observed survival benefit. Clinical trial information: NCT01099423.
Nephrectomy after complete response to immune checkpoint inhibitors for metastatic renal cell carcinoma (mRCC): A new surgical challenge?
Authors: Pignot Geraldine , Thiery-Vuillemin Antoine , Walz Jochen , Lang Herve , Werle Pierre , Balssa Loic , Geoffrois Lionnel , Leblanc Louis , Albiges Laurence , Di Nunno Vincenzo , Bensalah Karim , Ladoire Sylvain , Gravis Gwenaelle , Barthelemy Philippe 
Published: February 2020

707 Background: In the current era of Immune checkpoint inhibitors (ICI), the role and timing of nephrectomy in the case of complete response on metastatic sites is still unknown. We aimed to evaluate the feasibility of nephrectomy for residual disease in patients with metastatic renal cell carcinoma (mRCC) and complete response (CR) on metastatic sites following ICI. Methods: Patients who underwent partial or radical nephrectomy after prior ICI between 2015 and 2018 were retrospectively included and clinicopathological data were reviewed. Perioperative data and postoperative outcomes were recorded. Results: Eleven patients without initial cytoreductive nephrectomy at diagnosis underwent delayed nephrectomy after long ICI administration because of complete response on metastatic sites. Median age was 59.8 years [38-67]. All patients had clear cell RCC on the initial biopsy. IMDC prognostic group was intermediate (81.8%) or poor (18.2%). ICI was administered as first-line therapy in 36.4% of cases (4/11) and as second-line option after TKI in 63.6% of cases (7/11). Treatments regimens were: nivolumab + ipilimumab (n = 3), nivolumab + tivozanib (n = 2) or nivolumab alone (n = 6). The median duration of ICI treatment was 10 months (range: 3-38 months) and the mean number of cycles was 27 (range: 6-75). Median operative time was 243 minutes [135-345] and mean blood loss was 909 cc [40-4000]. In 81.8% (n = 9) of the cases, surgeons experienced challenges for finding dissection planes due to inflammatory infiltration. The 30-day Clavien-Dindo postoperative complication rate was 54.6%, including 1 surgery-related death. Pathological report showed lymphocyte and/or macrophage infiltration in 54.6% and complete pathological response in 2 cases. Median follow-up was 15 months, with 73% of patients free from progression and 54% free from systemic treatment at 1 year. Conclusions: Nephrectomy following ICI for mRCC could allow achieving CR in selected patients. Due to technically complexity and complications rates, this surgery should be performed in centers with extensive experience.
A systematic review and network meta-analysis of first-line treatment options in patients metastatic renal cell carcinoma.
Authors: Riaz Irbaz Bin , Ryu Alexander J. , Yao Yuan , Siddiqi Rabbia , Mathew Jessey , Sipra Qurat Ul Ain Riaz , Zahoor Haris , Wang Zhen , Murad M. Hassan , Pagliaro Lance C. , Costello Brian Addis 
Published: February 2020

709 Background: Several immunotherapy (IMT) combinations either as an IMT doublet or IMT in combination with TKIs are now available for first-line therapy of metastatic renal cell carcinoma (mRCC). In the absence of head-to-head clinical trials, we performed an indirect comparison of frontline treatment options to provide clinical guidance. Methods: Medline, Embase and Cochrane Library were searched to identify relevant trials. Hazard ratios (HR) and confidence interval (CI) for primary outcome of progression-free survival (PFS) and secondary outcome of overall survival (OS) were abstracted. Network meta-analysis was performed using a multivariate, consistency model, random-effects meta-regression. Data on Grade 3 or higher AEs was abstracted and meta-analyzed. Pre-specified subgroup analyses were performed based on risk categories (high risk vs low and intermediate vs), history of prior nephrectomy, PD-L1 positivity, age and sex. Risk for bias(RoB) was assessed using the Cochrane Collaboration’s tool. Results: Nine studies were included for PFS analysis, and 6 studies for OS analysis. Avelumab-axitinib (AA) (HR 0.69, 0.48-0.96), and Pembrolizumab-Axitinib (PA) (HR 0.89, 0.50-0.96) significantly improved PFS, while there was no significant PFS benefit with atezolizumab-bevacizumab (AB) (HR 0.83, 0.62-1.13) and nivolumab-ipilimumab (NI) (HR 0.85, 0.63-1.15) as compared to Sunitinib. PA (HR 0.53, 0.38-0.75) and NI (HR 0.63, 0.44-0.90) significantly improved OS, while AB (HR 0.93, 0.75-1.12) showed no significant OS benefit as compared to Sunitinib. NI and AB had significantly fewer grade ≥3 AE than sunitinib. No significant interaction was found by risk group, age, sex or prior nephrectomy. Significant interaction was found by PD-L1 expression(p<0.001), with significant PFS improvement in PD-L1 positive (HR 0.62, 0.53-0.73) but not in PD-L1 negative patients (HR 0.92, 0.81-1.05). Overall, RoB was low amongst included studies. Conclusions: AA improved PFS, NI improved OS, whereas PA improve both PFS and OS as compared to sunitinib monotherapy. However, no IMT combination was superior to other combinations. Cost effectiveness analysis will be reported separately.