bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison between oncological outcomes of primary versus salvage radical cystectomy for urothelial carcinoma of the bladder.
Authors: Ladi Seyedian Seyedeh Sanam , Bateni Zhoobin , Bazargani Soroush T. , Zainfeld Daniel , Cai Jie , Miranda Gus , Ballas Leslie , Bhanvadia Sumeet , Schuckman Anne K. , Djaladat Hooman , Daneshmand Siamak
Published: February 2020

585

Background: This study aims to compare oncologic outcomes among patients who underwent salvage radical cystectomy (sRC) for recurrent urothelial carcinoma (UC) of the bladder following radiotherapy (RT) with primary radical cystectomy (pRC). Methods: We retrospectively reviewed the data of 3705 primary consented cystectomy patients of our IRB-approved bladder cancer database from Jan 1971 to June 2017 who underwent radical cystectomy for urothelial carcinoma of the bladder. Clinical and pathological data at the time of both RT and RC was collected. Patients with non-UCs and those receiving radiation for non-UCs were excluded. Multivariate analyses was performed to identify prognostic factors after RC for overall survival and recurrence-free survival. Results: 3050 patients were identified who underwent radical cystectomy for UC of the bladder. Of these, 128 patients (4.2%) underwent sRC following radiotherapy (RT). Patient characteristics including age, BMI, gender, and comorbidities were similar between the groups. Complications rates between the groups were similar at 30 days (43% sRC vs 39% pRC patients, p=0.41) and 90 days (52% sRC vs 48% pRC, p=0.42). Patients receiving sRC were less likely to receive a continent diversion (p<0.001). Five-year overall survival following sRC was 47% in comparison to 63% for those undergoing pRC (p<0.001) (Fig 1). However, no significant difference in five-year recurrence free survival was found (61% sRC vs 68% pRC; p=0.15). On multivariate analysis, sRC (HR 1.37, p=0.048), pathologic tumor stage ≥pT3a (HR 2.6, P < 0.001) and lymph node metastases (HR 2.5, P < 0.001) were associated with increased risk of local recurrence after radical cystectomy. Conclusions: Patients undergoing sRC are less likely to receive a continent urinary diversion and are at increased risk of local recurrence following cystectomy in comparison to patients receiving primary cystectomy.
Salivary proteomic profile of patients with renal cell carcinoma.
Authors: Balasubramanian Adithya , Zhou Weidong , Petricoin Emanuel , Streckfus Charles F. , Klein John R , Qiao Wei , Wood Christopher G. , Karam Jose A. , Lozano Marisa , Matin Surena F.
Published: February 2020

622

Background: We aimed to explore the salivary proteomic profile (SPP) of patients undergoing surgery for suspected renal cell carcinoma (RCC), then evaluate any significant findings in a validation cohort. Methods: Prospective IRB approved trial of consecutive patients with suspected RCC undergoing curative surgery. Saliva was collected pre- and postoperatively, and from healthy volunteers. Saliva was mixed with sodium orthovanadate and protease inhibitor, aliquoted, and frozen at -80oC. SPP performed using biomarker concentrated saliva via core-shell hydrogel nanoparticles functionalized with molecular baits coupled to high resolution MS/MS electrospray mass spectrometry analysis; output represented as spectral counts. Wilcoxon Rank Sum test was used for comparisons; p-values were adjusted using false discovery rate (FDR) for multiple testing. Results: Exploratory phase: saliva was collected from 27 volunteers and 34 RCC patients (24 clear cell (cc)RCC, 6 chromophobe (ch)RCC, 4 other). Evaluation of cc vs chRCC revealed differential counts for 56 proteins; none were significant after adjustment by FDR. Comparison of matched pre/post-operative SPP in 14 ccRCC patients identified differential counts of 3 proteins: basic salivary proline-rich protein 3 precursor; prolactin-inducible protein precursor; and submaxillary gland androgen-regulated protein 3B precursor. These were not affected by patient age, partial/radical nephrectomy, or tumor size/stage/grade. Validation phase: power analyses indicated a sample size of 38/53 patients = 90% power = effect size of 0.6/0.5, respectively, 2-sided Type 1 error of 0.025. 49 ccRCC patients were enrolled with pre/postop saliva. 611 proteins were identified; none had differential counts after FDR. Conclusions: Using a unique biomarker technology coupled to high resolution MS, interesting SPP’s were seen between RCC subtypes and before/after ccRCC curative resection. We were unable to show significant differences in pre/post-op levels. More research is needed to further study the SPP in RCC patients and the factors impacting their differential expression. In order to aid such efforts, the raw data will be made available for future researchers.
Renal tumor biopsy to reduce overtreatment of renal oncocytomas.
Authors: Neves Joana B. , Withington John , Varley Rebecca , Agnesi Stefano , Capitanio Umberto , Grant Lee , Tran-Dang My-Anh , El-Sheikh Soha , Walkden Miles , Yuminaga Yuigi , Patki Prasad , Barod Ravi , Mumtaz Faiz , Bex Axel , Tran Maxine Gia Binh
Published: February 2020

623

Background: Up to 30% of renal masses are benign tumours, the most common of which is renal oncocytomas (RO). Our practice is to offer renal tumour biopsy (RTB) for small renal masses (SRM; ≤4cm) as part of a multi-disciplinary pathway. Our objective was to determine whether RTB influenced the management of RO. Methods: Retrospective descriptive analysis of the management of all sporadic cases with a histological diagnosis of RO (biopsy or surgical) at a high-volume tertiary centre from January/2012 to June/2019. Results: 170 patients (66% male; median age 67 years; median age-related Charlson comorbidity index 3) were diagnosed with 177 RO (median size 36mm). 70% (124) of RO were diagnosed using tumour biopsy (median size 33mm), of which 116 (93.4%) embarked on active surveillance (AS; 101) or watchful waiting (15). 53 (30%) RO were diagnosed after surgical excision (median size 50mm; 15 partial and 38 radical nephrectomies), of which 4 lesions were initially managed with AS. Median follow-up on AS was 20 months (2 to 84 months), with a median decrease in estimated glomerular filtration rate of 3 ml/min/1.73m2 over this period. 79% of RO on AS were SRMs. Median overall lesion size change was 1.1mm/year during follow up. Overall 62.6% of lesions grew, a quarter of which at a rate >5mm/year. Nine cases of RO on AS changed to intervention due to lesion growth or patient choice. No metastases were reported in the whole cohort. Three patients on AS died (stroke, respiratory arrest secondary to food inhalation, and unknown cause). One patient who had had surgical excision of RO died of unknown cause. Conclusions: Surgical risks for benign renal lesions are not different to those taken for renal cell carcinoma. RTB reduces the use of unnecessary surgery and its incumbent morbidity for benign renal lesions, such as RO. AS is a safe management option for patients with RO and can be used to reduce overtreatment-associated harm.
Treatment response comparisons between ATM and BRCA2 germline carriers for mCRPC.
Authors: Sokolova Alexandra , Marshall Catherine Handy , Lozano Rebeca , Grivas Petros , Higano Celestia S. , Lotan Tamara L. , Montgomery Robert B. , Nelson Peter , Olmos David , Schweizer Michael Thomas , Yezefski Todd , Yu Evan Y. , Paller Channing Judith , Castro Elena , Antonarakis Emmanuel S. , Cheng Heather H.
Published: February 2020

63

Background: Over 10% of men with metastatic prostate cancer (PC) have germline DNA damage response gene alterations; most studies have reported BRCA2 alone or an aggregate of BRCA1, BRCA2 and ATM. Emerging data suggest ATM mutations have distinct effects and warrant individual gene evaluation. We hypothesize that, compared to patients (pts) carrying germline BRCA2 mutations (g BRCA2mut), pts carrying germline ATM mutations (g ATMmut) may have different treatment response to androgen-receptor-targeted agents, docetaxel, platinum therapy and PARP inhibitors (PARPi). Methods: This is an international, multicenter, retrospective case-control study of pts with PC who underwent clinical germline genetic testing between 2014-2019. We identified pts with g ATMmut and matched pts with g BRCA2mut by stage at diagnosis and year of testing. IRB-approved medical records review, χ² and log rank tests were performed. Results: 39 g ATMmut cases and 39 matched g BRCA2mut cases were identified for total of 78. A third (13/39) of pts in each cohort had metastases at diagnosis. Of those diagnosed with localized stage, 81% (21/26) of gATMmut and 73% (19/26) of g BRCA2mut developed metastasis (median times to metastasis 69 vs 49 months, respectively (p=0.1)). Pts in g ATMmut and g BRCA2mut cohorts had similar age, Gleason grade, and PSA at diagnosis. We did not observe a difference in PSA50 response rates to abiraterone, enzalutamide, docetaxel, or carboplatin for mCRPC (Table). g BRCA2mut pts were more likely to respond to PARPi for mCRPC; where available, somatic loss of heterozygosity (LOH) data will be reported at final presentation. Conclusions: While response to standard therapies appears similar between g ATMmut and g BRCA2mut cohorts, response to PARPi in g ATMmut appears to be attenuated compared to g BRCA2mut. More studies are needed and pts with g ATMmut warrant prioritization for novel treatment strategies.[Table: see text]
Safety and efficacy of tivozanib in first-line metastatic renal cell carcinoma: A multicenter compassionate use study.
Authors: Basso Umberto , Procopio Giuseppe , Fornarini Giuseppe , Massari Francesco , Bearz Alessandra , Fratino Lucia , Milella Michele , Bassanelli Maria , Sacco Cosimo , Bimbatti Davide , Verzoni Elena , Rizzo Mimma , Porta Camillo
Published: February 2020

632

Background: Tivozanib-TIVO is a potent and selective tyrosine kinase inhibitor of vascular endothelial growth factor receptor 1 (VEGFR1), VEGFR-2, and VEGFR-3. TIVO was recently approved in Europe for the first line treatment of metastatic Renal Cell Carcinoma-RCC after a randomized trial demonstrated improved PFS and different safety profile compared to sorafenib. Methods: Retrospective analysis of safety and activity of TIVO administered within a compassionate use program to pts with metastatic RCC with no prior systemic treatment. Results: From Aug 2018 to Apr 2019, 64 pts have started TIVO at 1,34 mg daily (three weeks on, 1 week off) in 9 Italian Oncology Units. Median age was 67.5 years (range 40 to 85), 61% males, median creatinine clearance 63 ml/min(range 30-97). According to IDMC criteria, 27.5 % of pts were good prognosis, 60% intermediate and 10.5 % poor. Primary tumor had been removed in 70.5% of pts. Histology was clear cell 89.5%, papillary 4.5%, unclassified 6%. Response rate was 46.5%, stable disease 37.5%, progression 16%. Grade 3-4 toxicities were 4.5% hypertension, 3% mucositis, 1.5% diarrhea and 1.5% anorexia. Dose reduction to 0.89 mg was applied to 15.5% of pts. PFS and OS data will be presented at the Meeting. Conclusions: TIVO showed good activity and favorable safety profile in a real world cohort of unselected pts with metastatic RCC. Predictive biomarkers of response to antiangiogenic therapy are urgently needed in order to identify RCC pts who should receive VEGFR inhibitors in the first line.
Immune checkpoint inhibitors (ICI) in clear cell renal cell carcinoma (ccRCC) following high-dose interleukin-2 (IL-2).
Authors: Elias Roy , Bowman Isaac Alexander , Hammers Hans J. , Brugarolas James
Published: February 2020

635

Background: IL-2 can be curative in a small subset of ccRCC patients (pts). Recent data suggest that ICIs may lead to long lasting responses, and ICI therapy following progression on IL-2 seems reasonable. However, data regarding the safety and efficacy of ICI following IL-2 is limited. Methods: ccRCC pts treated with ICI after first line were identified at UT Southwestern Medical Center from 2014 – 2018 and assessed by comparison to IL-2 naïve pts at the time of ICI initiation. Outcomes included objective response rates (ORR) determined by RECIST v1.1, time to next treatment (TNT) and overall survival (OS). Immune-related adverse events (irAEs) were graded per CTCAE v4.0. Comparisons were performed using Pearson Chi-square, independent t-tests, and Fischer’s exact tests as appropriate. The log-rank test was utilized for Kaplan-Meier survival analyses. Results: We identified 127 ccRCC pts treated with ICI after first line, 17.3% (22) who had received prior IL-2 and 83.7% (105) who were IL-2 naïve. Pts in the IL-2 group were younger (mean age, 56 vs. 63 years; p=0.003), and more heavily pretreated (median 2 prior lines vs. 1; p <0.0001). The distribution by IMDC criteria was similar with 86.4% (19) and 76.4% (81) in intermediate/ poor group in IL-2 vs. IL-2 naïve groups, respectively (p = 0.431). The ORR was 9.1% (2/22) vs. 21.2% (22/104) in the IL-2 vs. IL-2 naïve groups, respectively (p=0.244). The median TNT was 7.5 (95% CI: 1.8 to 13.2) vs. 9.2 (95% CI: 6.0 – 12.4; p= 0.667) months in the IL-2 vs. IL-2 naïve groups, respectively. The median OS was 26.4 (95% CI: 17.3 – 35.5) vs. 29.8 (23.1 to 36.4) months in the IL-2 vs. IL-2 naïve group, respectively. 18.2% (4) vs. 21.9% (23) pts developed a grade 3/4 irAE in the IL-2 vs. IL-2 naïve group, respectively (p=0.698). Conclusions: Our study suggests that ICI therapy following treatment with high-dose IL-2 remains efficacious and is not associated with an increased risk of irAEs.
Efficacy and safety of lenvatinib in combination with everolimus in metastatic renal cell carcinoma resistant to antiangiogenic targeted therapy: Russian multicenter observational study ROSLERCM.
Authors: Volkova Maria , Abdelgafur Ahmed , Amoev Zurab , Aivazov Magomed , Babina Ksenia Gennadievna , Borisov Pavel S. , Evstigneeva Irina , Samuseva Olga Igorevna , Kalpynsky Alexei , Karabina Elena , Kirdakova Natalia , Kuzmina Evgeniya , Latipova Dilorom H. , Ovchinnikova Elena G. , Olshanskaya Anna Sergeevna , Protsenko Svetlana , Semiglazova Tatiana , Smirnov Roman , Usynin Evgeny , Chernyakova Irina ,   ROSLERCM
Published: February 2020

644

Background: an assessment of efficacy and safety of lenvatinib in combination with everolimus in unselected patients with metastatic renal cell carcinoma (mRCC) progressed during or following ≥1 line of antiangiogenic targeted therapy. Methods: Russian multicenter observational study included 73 consecutive patients with morphologically verified mRCC progressed during or following ≥1 line of antiangiogenic targeted therapy, treated with lenvatinib (18 mg/d) and everolimus (5 mg/d) in 20 Russian centers. Median age of the patients was 59 (23-73) years, a male-to-female ratio - 3:1. Most common histological type of kidney cancer was clear-cell RCC (71 (95.8%)). More than 2 lines of previous treatment were administered in 45 (61.6%) cases. Most patients were diagnosed with multiple metastases (71 (97.3%)) in >1 site (61 (83.6%)). Nephrectomy was performed in 87.7% (64/73) of cases. At the combined therapy start ECOG PS 2-4 was registered in 16 (20.5%), poor prognosis according to IMDC score – in 33 (45.2%) patients. Median follow-up was 9.7 (1-26) months. Results: objective response rate was 11% (8/73); tumor control was reached in 93.2% (68/73) of cases. Median objective response duration was 10.5 (4.3-16.8) months, tumor control duration – 10.0 (2.5-17.5) months. Median progression-free survival (PFS) achieved 16.9 (95% confidence intervals (CI): 12.1-20.6), overall survival (OS) – 20.8 (95% CI: 15.7-25.9) months. Any adverse events (AE) developed in 83.6% (61/73), AE grade 3-5 - in 23.3% (17/73) of cases. Most frequent AE grade 3-4 were diarrhea (10 (13.6%)) and arterial hypertension (6 (8.2%)). Unacceptable toxicity demanded treatment cancellation in 4.2% (3/73), therapy interruption – in 30.1% (22/73) and dose reduction – in 32.9% (24/73) of patients. Conclusions: unselected mRCC patients administered with combined targeted therapy in the real world practice were registered with lower objective response rate, similar survival and better tolerability comparing with population assigned for lenvatinib plus everolimus in the randomized phase II trial.
A novel multiplex score to predict outcomes of partial nephrectomy for multiple tumors.
Authors: Chalfin Heather , Yerram Nitin , Gurram Sandeep , Linehan W. Marston , Ball Mark Wayne
Published: February 2020

656

Background: The RENAL nephrometry score (RNS) is widely used to describe renal mass complexity and inform patient counseling for partial nephrectomy (PN). However, in cases with multiple lesions (commonly seen in hereditary cancer syndromes) it is unknown which features drive postoperative complications. Here, we employed a novel scoring equation (Multiplex Score, MS) derived from RNS and assessed outcomes of multiplex PN at our institution. Methods: The MS was defined a priori as a weighted score (# low risk (LR) lesions) + 2*(# intermediate risk (IR)) + 4*(# high risk (HR)) based on published Clavien-Dindo III-V complication rates of 6.4%, 11.1%, and 21.9% for LR, IR, and HR RNS respectively. MS was dichotomized into favorable/unfavorable based on median score. Patient outcomes were maintained prospectively. Binary outcomes were evaluated with logistic regression and continuous outcomes were evaluated with linear regression. Results: From 10/2017-8/2019, 62 consecutive multiplex PN (median (range) # tumors = 4 (2-11), 65% robotic) were performed by a single surgeon. Median (range) MS was 6 (2-20). Of 13 complications, urine leak (N = 5, 8%) and bleed requiring embolization (N = 4, 6%) were the most common. Only 1 complication occurred in the favorable score group and MS was significantly associated with perioperative complication (OR 1.21, p = 0.018) and blood loss (242.42 mL, p < 0.001). Hilar clamping was omitted in 32 (52%) cases with median 18.5 min when used. Every 1 additional HR or IR tumor was associated with a 2 minute increase in clamp time (2.01, p = 0.048). Median clamp time for favorable/unfavorable cases was 0 vs. 10 minutes. Change in renal function was negligible in our cohort (median ΔCr 0 mg/dL, IQR -0.61–0.1). There were no conversions from partial to radical nephrectomy and open conversion was only done in 3 (7.5%) cases, all assigned unfavorable MS. Conclusions: The novel Multiplex Score associated well with complications, blood loss, and open conversion. This tool may facilitate standardized reporting of complexity for multiplex series, with special relevance for hereditary cancer syndromes.
Neutrophil-to-lymphocyte ratio as a predictor of oncologic outcomes in locally advanced non-metastatic clear cell renal carcinoma.
Authors: Rodrigues Gilberto , Sierra Pablo , Albuquerque Emanuel , Gallucci Fabio Pescarmona , Ilario Eder Nisi , de Carvalho Paulo Afonso , Muniz David Queiroz Borges , Sarkis Alvaro , Coelho Rafael , Cordeiro Mauricio , Nahas William Carlos
Published: February 2020

661

Background: An elevated neutrophil-to-lymphocyte ratio (NLR) has been associated with worse oncologic outcomes in several malignancies, its prognostic role in kidney cancer, specifically in the non metastatic setting is controversial. We aimed to evaluate if an elevated NLR in patients with locally advanced non metastatic clear cell renal cell carcinoma (CCRCC) is associated with a worse survival and/or a higher cancer recurrence rate. Methods: We retrospectively identified 880 nephrectomies performed between 01/2009 to 12/2016 in a single center, reviewed data from 478 consecutive radical nephrectomies (RN) for kidney tumors and identified 187 patients with locally advanced non-metastatic CCRCC patients (pT3-T4 N0M0). The cut-off point of NLR = 2.5 was obtained using the receiver operating curve analysis (ROC). NLR was obtained preoperatively and calculated by dividing absolute neutrophil count by absolute lymphocyte count. Overall survival (OS) and recurrence-free survival (RFS) were evaluated using the Kaplan-Meier method. Cox regression models were utilized to evaluate predictors of recurrence and survival. Results: Median follow up was 48.7 months. The 3 year OS was significantly lower for patients with NLR ≥ 2.5 than those with NLR < 2.5 (70% vs 85%, p = 0.049). In patients with a Fuhrman nuclear grade of differentiation of 3-4, the median time to recurrence was significantly shorter for patients with NLR ≥ compared to those with NLR < 4 (24 vs 55 months p 0.045). On multivariable analysis adjusted for NLR ≥ 2.5, microvascular invasion, sarcomatoid differentiation, tumor size and body mass index, only nuclear grade of differentiation was found to be an independent predictor for recurrence (hazard ratio= 2.18; 95% confidence interval [CI]: 1.07 – 4.92, p = 0.03). Conclusions: Patients with non-metastatic CCRCC with higher nuclear grade of differentiation and a high preoperative NLR have shorter RFS and worse OS compared to patients with lower NLR.
Does delay in time to surgery impact outcome in renal cell carcinoma: Analysis based on tumor size utilizing the National Cancer Database.
Authors: Patel Devin , Ghali Fady , Meagher Margaret , Bradshaw Aaron , Patel Sunil , Murphy James Don , Derweesh Ithaar
Published: February 2020

664

Background: The impact of delay in treatment for localized renal cell carcinoma (RCC) is controversial. We sought to determine the survival impact of time to definitive surgical treatment stratified by tumor size in a group of young, healthy patients from the National Cancer Database (NCDB). Methods: The NCDB was queried for cases of localized RCC (cT1-T3N0M0) in patients <60 years of age with Charlson comorbidity score of 0 from 2004-2015. Quartiles were formed from the range of time to surgery of the entire cohort in days, with delayed treatment as the fourth quartile. Tumors were stratified into size of <2 cm, 2-4 cm, 4-7 cm and >10 cm. Overall survival (OS) between early and delayed groups was calculated with Kaplan-Meier analysis (KMA) and multivariable cox proportional hazards (MVA) and stratified by tumor size. Logistic regression was performed to determine factors associated with delay in surgical care. Results: 44,149 patients were analyzed. Median time to treatment was 35 days (IQR 19-61). Early (n = 33,144) and delayed (>61 days, n =11,005) groups had a mean follow-up of 61.5 and 57.5 months, respectively (p < 0.001). KMA showed worse 5-yr OS in patients with surgery delay versus no delay for tumors 2-4 cm in size (5-yr OS 49% vs. 54%; p<0.001), 4-7 cm (5-yr OS 47% vs. 53%; p<0.001), >7 cm (5-yr OS 45% vs. 49%;p=0.0002), but not for tumors <2 cm (5 yr OS 49% vs. 51%: p=0.5848). MVA showed worse OS with surgery delay compared to no surgery delay in patients with tumor size 2-4 cm (HR 1.24; 95%CI 1.09-1.42), 4-7 cm (HR 1.32; 95%CI 1.16- 1.50) and >7 cm (HR 1.14; 95%CI 1.01-1.30) but not tumors <2 cm (HR 0.83; 95% CI 0.65-1.05). Delay in treatment was higher with older age (OR 1.01; p<0.001), male gender (1.11; p<0.001), non-private insurance (OR 1.44; p<0.001), black race (OR 1.60; p<0.001), decreased education (OR 1.11; p<0.001) and tumors >2 cm (OR 1.23; p<0.001). Conclusions: In patients <60 years of age and CCI of 0, delay in treatment was associated with worse OS for tumors >2 cm but not for RCC <2 cm in size. While these findings support data suggesting that active surveillance for RCC < 2 cm in size is appropriate even in young and healthy patients, caution should be exercised in patients with tumors > 2 cm.
Prognostic understanding in advanced genitourinary cancer and its association with clinical characteristics.
Authors: Bergerot Cristiane Decat , Philip Errol James , Bergerot Paulo Gustavo , Salgia Nicholas , Salgia Meghan , Hsu Joann , Dizman Nazli , Pal Sumanta K.
Published: February 2020

665

Background: Despite promotion of a shared decision-making model of care in oncology, studies suggest that many patients with advanced cancer still possess inaccurate perceptions of their prognosis. Such inaccuracies can influence treatment choices, patient satisfaction and care planning. Novel immunotherapies and targeted treatments, which can yield exceptional responses in a small proportion of patients, are making the difficult task of discussing prognosis with patients even more challenging. We sought to identify clinical factors associated with expectations of cure. Methods: A cross-sectional survey study was conducted among patients diagnosed with incurable genitourinary cancers. Patients’ expectations of cure were assessed based on 4 quartiles: (1) cure is very likely and is in the range of 76 to 100% certainty, (2) cure is likely and is in the range of 51 to 75% certainty, (3) cure is possible but not likely and is in the range of 26 to 50% certainty, and (4) cure is not at all likely and is in the range of 0 to 25% certainty. Linear regression was used to identify clinical factors associated with such expectations. Results: A total of 145 patients were enrolled in the study from July 2017 to September 2019. Most patients were male (76%), white (70%), married (81%) and well-educated (76%). Patients were diagnosed with advanced kidney (66%), bladder (20%) or prostate (14%) cancers. A high proportion of patients (73%) were receiving first or second line (1L/2L) therapy; predominantly immunotherapy (53%) and targeted therapy (24%). Overall, 47% had an inaccurate expectation of cure (in the range of 26 to 100%). Inaccurate expectations of cure were associated with older age (P=0.04) and were also more likely to be reported among patients receiving 1L/2L compared to those receiving later courses of therapy (P=0.009). Conclusions: Our findings highlight the high proportion of patients harboring inaccurate perceptions regarding prognosis, more pronounced with older age and within the first two lines of therapy for metastatic disease. These groups may be ideal target populations for more extensive counseling around prognosis.
Impact of facility volume on complications from immunotherapy for renal cell carcinoma.
Authors: Cone Eugene Blanchard , Wang Ye , Reese Stephen , Chang Steven Lee
Published: February 2020

672

Background: Better outcomes have been generally associated with higher volume providers/hospitals. Recent work found an association between higher volume facilities and survival for advanced cancer patients. Volume and treatment complications for medical cancer therapy is unexplored. We studied a retrospective cohort of patients with metastatic renal cell carcinoma receiving immunotherapy at high and low volume hospitals. Methods: We used Premier Healthcare Data, which includes administrative data from all payors at over 700 community and academic hospitals, and captures 20% of all hospital discharges in the US, including infusions performed in hospital clinics. Using ICD9 codes we identified patients with metastatic renal cell carcinoma treated with nivolumab from 2015-17. Clinicodemographic data were obtained for patients and hospitals. The primary exposure was dichotomized hospital treatment volume (top quartile = high volume). Outcomes were immunotherapy-related complications for which the patient re-presented to the Emergency Department or was readmitted, and readmission for other cause. We performed mixed effects logistic regression adjusting for complex survey design to achieve national representation. Results: We included 15,724 weighted hospital encounters (5,835 at low-volume hospitals and 9,889 at high-volume hospitals). Urban, teaching hospitals were more likely to be high volume, but all patient factors were balanced. We observed 1,457 complications at high volume hospitals and 1,734 at low volume hospitals. There were no significant differences by volume of hospital in overall rates of complications (OR 0.92, 95% CI 0.82-1.09) or in rates of individual complications, with the exception of ocular complications (n=11, all low volume hospitals). We observed that high volume hospitals significantly reduced odds for readmission (OR 0.09, 0.03-0.24) unrelated to immunotherapy complications. Conclusions: We found no difference in immunotherapy-related complication rates by facility volume. This is reassuring for community administration of immunotherapy. Further study is needed to elucidate why we saw significantly more therapy-unrelated readmissions at lower volume hospitals.
Relative risk of pneumonitis associated with first-line use of immune checkpoint inhibitors in advanced renal cell carcinoma.
Authors: Jahan Nusrat , Mogollon-Duffo Francis , Meda Srikala , Hardwicke Fred L. , Tijani Lukman Aderoju
Published: February 2020

676

Background: After approval in 2006, sunitinib remained the standard for the first line treatment of advanced renal cell carcinoma (aRCC) for a decade. Immune checkpoint inhibitors (ICI) have changed the landscape of aRCC management in recent years. Pneumonitis is a significant immune related adverse event (iRAE) associated with ICIs causing morbidity, mortality and treatment interruption. We conducted a meta-analysis of phase 3 randomized controlled trials (RCTs) to determine the relative risk of pneumonitis associated with first line use of ICIs for aRCCs. Methods: We conducted a systematic search using PUBMED, MEDLINE, EMBASE, and meeting abstracts as per PRISMA guidelines from inception until May 2019. Phase 3 RCTs using ICIs in the intervention arm for the first line treatment of aRCC and reporting the number of pneumonitis for both intervention and control arms were included in the analysis. We used the Mantel-Haenszel (MH) method utilizing random effects model to calculate pooled risk ratio (RR) with 95% confidence interval (CI). Heterogeneity was tested with I2 value. Results: Three phase 3 RCTs, CheckMate 214, IMmotion151 and KEYNOTE-426, randomizing 2833 patients (1427 in the ICI arms and 1406 in the control arms) were included in the analysis. ICI regimens used in the study arms were as follows — CheckMate 214: nivolumab and ipilimumab, IMmotion151: atezolizumab and bevacizumab, and KEYNOTE-426: pembrolizumab and axitinib. Sunitinib was used for all the control arms. Randomization was 1:1 in all three studies. Pneumonitis of any-grade was reported in 56 (3.92%) patients in the ICI arms versus 1 (0.07%) patient in the control arms. The pooled RR of any grade pneumonitis was 22.11 (95% CI: 5.34-91.55, P<0.0001, I2=0%). Grade 3 and above pneumonitis was reported in 12 (0.84%) patients in the ICI arms versus 0 (0%) patient in the control arms with pooled RR of 8.39 (95% CI: 1.54-45.80, P=0.01, I2=0%). Conclusions: The relative risk of any-grade as well as high-grade pneumonitis are significantly higher with ICI based regimens compared to sunitinib for aRCC. Early detection and prompt intervention are vital to reduce morbidy and mortality associated with this iRAE.
Financial hardship among Medicare beneficiaries prescribed oral targeted therapies for advanced prostate cancer.
Authors: Caram Megan Veresh , Oerline Mary , Dusetzina Stacie , Modi Parth K. , Herrel Lindsey A. , Skolarus Ted A. , Hollenbeck Brent K. , Shahinian Vahakn B.
Published: February 2020

68

Background: Abiraterone and enzalutamide are increasingly being used to treat advanced prostate cancer. Understanding barriers to adhering to treatment is of paramount importance in ensuring continued access to these important therapies. Patients with limited resources or insufficient access to mechanisms that lower their out-of-pocket cost are likely to suffer from significant financial toxicity and may engage in coping mechanisms such as rationing or abandoning their medication. Methods: To address the variability in measures of financial hardship, we performed a retrospective cohort study on a 20% sample of patients eligible for Medicare Part D who received their first fill of abiraterone or enzalutamide between July 2013 and June 2015. Patients were assigned to a provider based on their first prescription, and a hospital referral region (HRR) based on their ZIP code. The primary outcomes were to determine the proportion of days covered (PDC), overall prescription adherence, and average monthly out-of-pocket cost to patients prescribed abiraterone or enzalutamide, all within the first six months of treatment. Results: From mid-2013 to mid-2015, 4529 patients filled abiraterone or enzalutamide through Medicare Part D, within 305 HRRs. There was substantial variability in PDC, adherence, and out-of-pocket cost to patients among HRRs. The mean PDC was 84% with mean adherence of 73%, which included the 393 (8.7%) of patients who abandoned oral therapy after 1-2 fills. The median standard monthly out-of-pocket cost was $707, ranging between $0 and $3505. Among patients with low-income subsidies, median out-of-pocket cost by HRR ranged from $0 to $2815. We observed that PDC tracked closely with socioeconomic status – HRRs that included a higher proportion of patients eligible for Medicaid had lower PDCs and adherence, but lower standard out-of-pocket cost. Conclusions: This investigation demonstrated significant variation in PDC, adherence, and out-of-pocket cost among different HRRs for patients prescribed abiraterone and enzalutamide and that much of the variability in financial hardship measures among HRRs may be due to socioeconomic variables and regional variability.
Real-world data of cabozantinib in patients with VEGF-refractory metastatic renal cell carcinoma (mRCC): Results from the French Early Access Program (CABOREAL).
Authors: Gross-Goupil Marine , Flechon Aude , Chevreau Christine , Topart Delphine , Gravis Gwenaelle , Oudard Stephane , Tourani Jean-Marc , Geoffrois Lionnel , Meriaux Emeline , Thiery-Vuillemin Antoine , Barthelemy Philippe , Ladoire Sylvain , Laguerre Brigitte , Perrot Valérie , Billard Anais , Escudier Bernard , Albiges Laurence
Published: February 2020

683

Background: Cabozantinib (Cabo) is approved in Europe for the treatment of mRCC in first line and after failure of tyrosine kinase inhibitors (TKI). We report the results from real-world use of Cabo in the French Early Access Program (EAP) (CABOREAL [NCT03744585]). Methods: Data were retrospectively collected from 26 centers. Patients (pts) were treated with Cabo during the Temporary Authorization for Use (ATU) period from Sep 12, 2016 to licensing in Feb 19, 2018. Pts were eligible after 2 prior VEGFR TKI unless clinical decision for 2nd line (L). The aim was to evaluate the use and activity of Cabo in real-life conditions. Overall survival (OS) was calculated from initiation of Cabo. Results: Overall, 410 pts were included. Median age was 63 years, 85% had clear-cell histology, 41% and 32% were intermediate/poor IMDC risk, respectively. Pts were mostly ECOG 1 (42%) or 2 (30%); 229 (56%) pts had bone metastasis (mets). Median follow-up was 14.4 months (m). Cabo was used as 2L, 3L and 4L or beyond for 101 (25%), 137 (33%) and 172 (41%) pts respectively; 204 pts (50%) were pretreated with nivolumab (Nivo). Activity results and dose reduction are summarized in the table. Starting dose was 60 mg (290 pts, 71%), 40 mg (109 pts, 27%) and 20 mg (8 pts, 2%). Treatment interruption occurred for 267 pts (65%), dose modification for 240 pts (59%) and schedule change for 64 pts (16%). Median daily dose was 40 mg/day. Treatment discontinuation occurred for 348 (85%) pts, with 86 (25%) due to adverse events. Notably, 184 (54%) pts received a subsequent systemic therapy. Conclusions: We report the largest real-world study of Cabo in mRCC to date. CABOREAL demonstrates that using dose modification, median Cabo duration was 7.6 m in a heavily pretreated population, with the longest treatment duration in patients with prior Nivo exposure. Clinical trial information: NCT03744585. [Table: see text]
Comparative cost-effectiveness analysis of avelumab plus axitinib versus pembrolizumab plus axitinib, ipilimumab plus nivolumab, and sunitnib for advanced renal cell carcinoma in the U.K. Perspective.
Authors: De Mello Ramon Andrade , Ayoub Emili , Castelo-Branco Pedro , De Almeida Zia Victor Andre , Savio Andre , Pozza Daniel Humberto , Tadokoro Hakaru , Teich Nelson
Published: February 2020

689

Background: Avelulmab plus axitinib showed to improve clinical outcomes for patients with advanced renal cell carcinoma (aRCC) in the JAVELIN RENAL 101 trial. Several other immunocheckpints inihibitos (ICIs) options acquired a main role in the aRCC treatment, such as nivolumab plus ipilimumab and pembrolizumab plus axitinib. Our aim is to evaluate the cost effectiveness of avelumab/axitinib versus other FDA approved options for previously untreated patients with aRCC. Methods: A Markov model was used to estimate the costs and health outcomes of treatment of aRCC with sunitinib, or avelumab plus axitinib. Univariable and probabilistic sensitivity analyses were performed to determine the robustness of the model outcomes. The primary outputs of the model included the total cost, life-years (LYs), quality-adjusted LYs (QALYs), and incremental cost-effectiveness ratio (ICER). Results: Avelumab plus axitinib provided and 4.77 additional QALY benefit. Total cost per patient was US$ 174,725 for avelumab/axitinib, US$ 178,725 for pembrolizumab/axitinib, US$ 169,390 for ipilimumab/nivolumab and US$ 97,846 for sunitnib. Avelumab/axitinib showed to be more cost-effective (ICER US$ 28,011/QALY) when compared to pembrolizumab/axitinib (ICER US$ 47,916/QALY) and ipilumumab/nivolumab (ICER US$ 95,392/QALY). Conclusions: Avelumab/axitinib is likely to be more cost-effective than ipilimumab/nivolumab, pembrolizumab/axitinib and sunitinib in the UK perspective. However further models, market discounts and stakeholders price negotiations could lead to variations of this scenario across the globe.
Phase II efficacy trial of pazopanib in nonclear cell metastatic renal cell cancer (mRCC): PINCR.
Authors: Costello Brian Addis , Ho Thai Huu , Perez Burbano Gabriela , Hillman David W. , Quevedo Fernando , Pitot Henry C. , Pagliaro Lance C. , Bryce Alan Haruo , Tan Winston , Joseph Richard Wayne , Leibovich Bradley C. , Castle Erik P. , Dronca Roxana Stefania , Kohli Manish
Published: February 2020

696

Background: A number of treatments for metastatic renal cell carcinoma (RCC) have been FDA approved since December, 2005. Trials evaluating these agents excluded non-clear cell histologies and therefore the efficacy of these treatments remains unclear in patients (pts) with metastatic non-clear cell RCC (mncRCC). Methods: This is a single arm Phase II study designed to determine the efficacy of pazopanib in mncRCC. Treatment was pazopanib 800 mg by mouth daily until progression or intolerability of treatment. Dose reductions were allowed for toxicity with dose level -1 being 600 mg daily and dose level -2, 400 mg daily. Cycles were every 28 days. Main eligibility criteria included: (1) age ³ 18 years old; (2) histologic confirmation of ncRCC; (3) ECOG Performance Status (PS) 0, 1, or 2; (4) up to one prior treatment for mncRCC (5) measurable or non-measurable metastatic disease per RECIST criteria. The primary endpoint was overall survival rate at 12 months. Secondary endpoints were best tumor response rates after two cycles, PFS, OS and toxicity. Results: 38 pts were enrolled between May 16, 2013 and February 1, 2018. 35 pts were evaluable for primary endpoint. Median age 63 years old and 22/35 (62.9%) were male. Most common histology was papillary RCC, 14/35 (40%), and most common number of metastatic sites was 1. 29/35 (82.9%) had prior nephrectomy and 30/35 (85.7%) had no prior systemic therapy. Median number of cycles was 5. 12-month OS was 65.7% (90% CI, 50.5-78.9%). Best response in first 2 cycles: PR 11%, SD 60%, PD 9%, not evaluated 20%. Median PFS was 7.5 months (90% CI, 5.0-11.0); median OS 18.9 months (90% CI, 13.0-NE). Grade 3 / 4 AEs seen in 25 pts with hypertension, transaminitis and abdominal pain being most common (seen in >10%). Conclusions: There are limited data about the efficacy of available therapies for mncRCC. This study shows that pazopanib has similar efficacy compared to historical data in clinical trials using other TKIs in mncRCC. The safety profile of pazopanib in pts with mncRCC was found to be similar to that found in prior clinical trials studying pazopanib. Our findings warrant further investigation into the utility of pazopanib in metastatic ncRCC. Clinical trial information: NCT01767636.
Association of abiraterone and higher odds of cardiac complications compared to enzalutamide.
Authors: Cone Eugene Blanchard , Reese Stephen , Marchese Maya , Nabi Junaid , Kilbridge Kerry L. , Trinh Quoc-Dien
Published: February 2020

70

Background: The standard of care for advanced prostate cancer is androgen deprivation therapy (ADT). The novel second generation agents abiraterone and enzalutamide were initially approved in castration resistant disease, but are now being used in the hormone sensitive setting. The FDA issued a 2010 warning about cardiovascular risks associated with ADT, but the risk of novel agents is less well understood, especially in comparison to each other. We sought to define the comparative cardiac risk profile of enzalutamide and abiraterone. Methods: We used VigiBase, the World Health Organization database of individual case safety reports, which collects data from more than 130 countries to identify drug associated adverse events (AE). Using Medical Dictionary for Regulatory Activities terminology, we identified cardiac AEs related to abiraterone or enzalutamide therapy for prostate cancer. To explore a possible relationship we used the reporting odds ratio (ROR), a surrogate measure of association using all other reactions as non-cases. A lower bound of a 95% confidence interval of ROR > 1 reflects a disproportionality signal that more AEs are observed than expected due to chance. Results: Vigibase contained 8203 AEs for abiraterone and 26024 for enzalutamide; 808 (9.9%) were cardiac-related for abiraterone, and 1000 for enzalutamide (3.8%). We found no disproportionality signal for cardiac events or any subtype for enzalutamide, but identified significantly higher odds of overall cardiac events (ROR 1.64, 95% CI 1.53—1.76), myocardial infarction (1.34, 1.17—1.58), arrythmia (2.09, 1.87—2.34), and heart failure (3.35, 2.92—3.85) for patients taking abiraterone. Conclusions: Using validated pharmacovigilance methodology, we found significantly increased odds of cardiac events for abiraterone but not for enzalutamide. Clinicians may need to consider these findings in the context of their patients’ comorbidities when prescribing ADT.
Impact of age in advanced renal cell carcinoma treated with immune checkpoint inhibitors.
Authors: Carretero-González Alberto , Lora David , Carril Ajuria Lucía , Martin Soberón Maria Cruz , Castellano Daniel , de Velasco Guillermo
Published: February 2020

702

Background: Immune checkpoint inhibitors (ICIs) are beneficial in a subset of metastatic renal cell carcinoma (mRCC) patients. Elderly patients are usually under-represented in pivotal trials. Importantly, aging has been pointed as a potential detrimental factor for the benefit with ICIs as a consequence of the “immunosenescence” which could decrease the efficacy of these treatments. Methods: We assessed the potential role of aging according to Cochrane Collaboration's Guidelines. Search of randomized clinical trials (RCTs) comparing ICIs (monotherapy or in combination with other therapies) to standard of care (SoC) in mRCC patients was performed. Trials must have included subgroup analysis evaluating the selected outcome (overall survival-OS-) in different subsets of patients according to age. Additionally, a retrospective series of mRCC patients treated with ICIs from our institution was also reviewed to assess the impact of age. Results: A total of 3415 patients (4 studies) were included in the meta-analysis (ICIs arm: 1709 patients; SoC arm: 1706 patients). Altogether, OS results favored ICIs. Older patients (aged more than 75 years-old) seem to present a less clear benefit with ICIs compared to SoC in comparison with younger patients (aged up to 75 years-old; p-value for difference between subgroups: 0.006) (Table). No differences between subgroups were found when considering 65 years-old as the borderline (p-value: 0.179). A similar trend was found in our series, with a numerically better median OS in patients younger than 65 years-old compared to those older than 65 years-old (31,6 vs. 23,6 months); the effect of age on outcomes was maintained along all International Metastatic RCC Database Consortium (IMDC) score subgroups. Conclusions: Elderly patients with mRCC, particularly older than 75 years-old, could benefit to a lesser extent compared to younger counterparts from receiving ICIs.[Table: see text]
Immune checkpoint inhibitors plus tyrosine kinase inhibitors combination in the first-line setting of metastatic clear cell renal cell carcinoma: A meta-analysis of randomized clinical trials.
Authors: Martin Soberón Maria Cruz , Carretero-González Alberto , de Velasco Guillermo , Carril Lucia , Castellano Daniel
Published: February 2020

704

Background: ICIs + TKIs have shown to improve outcomes in treatment-naïve metastatic clear-cell renal cell carcinoma (ccRCC). We aimed to analize the efficacy of all combinations published including the subgroup analysis based on age, sex and IMDC prognostic factors score. Methods: We searched published RCTs in MEDLINE and EMBASE comparing ICIs + TKIs vs TKIs in 1L metastatic ccRCC. Outcomes selected to assess efficacy were progression-free survival (PFS), overall survival (OS) and objective response rate (ORR) in the intent-to-treat population. Hazard ratios (HR) for PFS and OS, and relative risk (RR) for ORR with 95% confidence intervals (CI) were used as efficacy measures. Subgroup-based meta-analysis was afterwards performed according to randomized-effect model. Results: We identified two eligible RCTs of ICIs + TKIs (avelumab [avelu] or pembrolizumab [pembro] + axitinib [axi]) versus TKIs (sunitinib). Combined sample size was 1,747 patients (avelu + axi arm 442 patients; pembro + axi arm 432 patients; sunitinib arm 873 patients). Globally, three outcomes favored the combination. Improved HRs for PFS (0.69), OS (0.64) and ORR (1.81) were found for combination (Table). Regarding subgroup analysis HRs for PFS were favorable for combination in male (0.665) and female (0.66). Benefit in combination arms was confirmed in terms of age < 65 years (0.68) and ≥ 65 years (0.66). Intermediate and poor IMDC subgroups showed statistically significant benefit for combination (HR 0.68 and 0.56), whereas PFS in favorable group (0.68) was not statistically significant. Conclusions: ICIs + TKIs combination therapy has consistently demonstrated to be superior in terms of OS, PFS and ORR in 1L ccRCC to TKIs alone. We hereby confirm statistically significant benefit per subgroups except for favorable IMDC subgroup.[Table: see text]