bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sunitinib versus cabozantinib, crizotinib or savolitinib in metastatic papillary renal cell carcinoma (pRCC): Results from the randomized phase II SWOG 1500 study.
Authors: Pal Sumanta K. , Tangen Catherine , Thompson Ian Murchie , Haas Naomi B. , George Daniel J. , Heng Daniel Yick Chin , Shuch Brian M. , Stein Mark N. , Tretiakova Maria S. , Humphrey Peter , Adeniran Adebowale , Narayan Vivek , Bjarnason Georg A. , Vaishampayan Ulka N. , Alva Ajjai Shivaram , Zhang Tian , Cole Scott Wesley , Plets Melissa , Wright John , Lara Primo "Lucky" N. 
Published: March 2021

270 Background: MET signaling is a key molecular driver in pRCC. Given that there is no optimal therapy for metastatic pRCC, we sought to compare an existing standard (sunitinib) to putative MET kinase inhibitors. Methods: Eligible patients had pathologically verified pRCC, Zubrod performance status 0-1, and measurable metastatic disease. Patients may have received up to 1 prior systemic therapy excluding VEGF-directed agents. Patients were randomized 1:1:1:1 to receive either sunitinib 50 mg po qd (4 wks on/2 wks off), cabozantinib 60 mg po qd, crizotinib 250 mg po bid, or savolitinib 600 mg po qd. Patients were stratified by prior therapy and pRCC subtype (I vs II vs not otherwise specified [NOS]) based on local review. The primary objective was to compare progression-free survival (PFS) for each experimental arm versus sunitinib. With 41 eligible patients per arm, we estimated 85% power to detect a 75% improvement in median PFS with a 1-sided alpha of 0.10 using intent-to-treat analysis. A pre-planned futility analysis was performed after 50% of PFS events occurred. Secondary endpoints included toxicity, response rate, and overall survival. Results: Between 4/2016 and 12/2019, 152 patients were enrolled; 5 were ineligible. Median age was 66 (range:29-89) and 76% were male; 92% had no prior therapy. By local pathologic review, 18%, 54% and 28% of patients were characterized as having type I, type II and NOS histology, respectively. In contrast, the frequency of type I, type II, and NOS by central review was 30%, 45% and 25%, respectively. Accrual to the savolitinib and crizotinib arms was halted early for futility (PFS hazard ratio > 1.0 for both); accrual continued to completion in the sunitinib and cabozantinib arms. Median PFS was significantly higher with cabozantinib relative to sunitinib (Table). Grade 3 or 4 adverse events occurred in 69%, 72%, 37% and 39% of patients receiving sunitinib, cabozantinib, crizotinib and savolitinib, respectively; one grade 5 adverse event was seen with cabozantinib. Overall survival and response data will be presented. Conclusions: In this multi-arm randomized trial, only cabozantinib resulted in a statistically significant and clinically meaningful prolongation of PFS in pRCC patients compared to sunitinib. These data support cabozantinib as a reference standard for eligible patients with metastatic pRCC. Clinical trial information: NCT02761057 . [Table: see text]
Patterns and predictors of oral anticancer agent utilization in diverse metastatic renal cell carcinoma patients.
Authors: Wheeler Stephanie B. , Spees Lisa , Jackson Bradford E , Baggett Christopher , Wilson Lauren E , Greiner Melissa A. , George Daniel J. , Scales Charles D. , Pritchard Jessica , Dinan Michaela Ann 
Published: March 2021

279 Background: Availability of targeted oral anti-cancer agents (OAA) has transformed care delivery for metastatic renal cell carcinoma (RCC) patients. Our objective was to identify patterns and predictors of OAA use within the 12 months after metastatic RCC was detected to understand the extent of real-world adoption of these treatment advances. Methods: We used a novel, North Carolina, registry-linked multi-payer claims data resource to examine patterns of use of sorafenib, sunitinib, pazopanib, everolimus, axitinib, cabozantinib, and levantinib in a cohort of metastatic RCC patients diagnosed over 10 years (2006-2015, with claims through 2016). Patients were required to have 12 months of pre- and post-metastatic-index-date continuous enrollment. Log-Poisson models estimated unadjusted and adjusted risk ratios (RRs) and 95% confidence limits (CLs) for associations between patient characteristics and OAA use. In sensitivity analyses, we used a competing risk framework to estimate adjusted risk differences (RD) in OAA use. Results: Our population-based study of 713 patients demonstrated relatively low (37%) OAA use at any time during the 12 months post-metastatic-index date among publicly and privately insured patients, with shifting patterns of use consistent with regulatory approvals over time. Lower OAA use was observed among patients who were older, frailer, and with greater comorbidity burden. Other patient-level characteristics, such as sex, race, rurality and type of insurance were not significant predictors of OAA use. Conclusions: These data underscore the importance of distinguishing clinically appropriate from potentially poor-quality care and warrant additional studies to understand in more depth the system, provider and patient level drivers of these patterns.
Real-world treatment patterns and sequencing for metastatic renal cell carcinoma (mRCC): Results from the Flatiron database.
Authors: George Saby , Faccone Jillian , Huo Stephen , Zhang Ying , Stwalley Brian , Hamilton Melissa , Le Trong Kim , Ejzykowicz Flavia 
Published: March 2021

286 Background: RCC accounts for ~80%‒90% of all kidney cancers worldwide. The mRCC treatment landscape is rapidly changing with the approval of new therapies; data describing real-world (RW) treatment patterns and sequencing are limited. This study investigates the characteristics, treatment patterns, and sequencing for mRCC patients in the RW (December 2015‒May 2020) and post-dual immuno-oncology therapy (IO-IO) approval in the United States (April 2018‒May 2020). Methods: Adults diagnosed with mRCC between December 2015 and May 2020 were selected from the Flatiron electronic medical record database for this retrospective study. The study cohort was required to have ≥ 1 month of medical data from the initial mRCC diagnosis date (index date). We used descriptive statistics to analyze baseline patient characteristics, treatment patterns, and sequencing. Results: Of 3,524 patients with mRCC (overall cohort, December 2015–May 2020), most were male (68.5%) and had clear cell histology (68.2%). The median age at metastatic diagnosis was 68 years (range, 23–85) and the median follow-up from index date was 328 days. Based on IMDC risk score, 75.8% of patients were categorized as intermediate/poor risk and 23.2% as favorable risk (1% missing). Systemic therapy for RCC was initiated in 79.1% (N = 2788) of patients. The most common treatments for first-line (1L) therapy were tyrosine kinase inhibitor (TKI) monotherapy (mono; 56.4%), IO-IO (19.1%), IO-TKI (9.5%), IO mono (6.9%), and others (8.1%). Second-line (2L) therapy was received by 1303 patients; treatment sequences are presented in the table below. Among patients who received IO-based therapy in the 1L (N = 990), 11% were retreated with IO on any subsequent line. When stratified by clear cell and non-clear cell histology, similar treatment patterns and sequences were observed. Among patients who initiated 1L treatment post-April 2018 (N = 1395), the most common treatments for 1L therapy were IO-IO (36.9%) and TKI mono (32.7%). Among patients who received 2L treatment after initiating 1L post-April 2018 (N = 486), TKI mono followed by IO mono, and IO-IO followed by TKI mono were the most prescribed sequences (Table). Conclusions: Following approval of IO-based therapies for 1L, RW treatment patterns for mRCC are evolving; IO-IO has become the most common 1L therapy received by all patients initiating treatment for mRCC. [Table: see text]
Use of nivolumab (N) and cabozantinib (C) for treatment of the metastatic renal cell carcinoma (mRCC) in the Veneto region: Results of AMOUR study.
Authors: Maruzzo Marco , Bortolami Alberto , Palleschi Dario , Zivi Andrea , Nicodemo Maurizio , Sartori Donata , De Vivo Rocco , Zustovich Fable , Bimbatti Davide , Pastorelli Davide , Vultaggio Giuseppe Dione , Soraru' Mariella , Ballestrin Melissa , Zanchetta Giulia , Modonesi Caterina , Randisi Paola , Barile Carmen , Perri Gino , Basso Umberto , Zagonel Vittorina 
Published: March 2021

290 Background: Second (2L) or third-line (3L) treatment options for mRCC have dramatically changed in the last years. The standard of care as per Italian Regulatory Agencies approvals is N or C. To date, there are no criteria for the choice between N and C, which both demonstrated OS gain in the pivotal trials. Methods: We planned a retrospective, real world analysis of the use of N and C as 2L and 3L treatment in 17 Oncology Units of Veneto Region. All consecutive patients (pts) with mRCC treated in advanced setting in 2017-2018 were included. Results: We identified 170 pts, 73% males, median age 68.4 years. All pts started a 2L treatment while only 59% received a 3L treatment. In our cohort, patients with NLR > 3 at treatment start had a shorter OS (43 vs 90 months (mos), p < 0.0001); IMDC classification maintained its prognostic role. In 2L, N was administrated in 108 pts (63%), C in 29 pts (17%); in 3L N was administrated in 42 pts (25%), C in 49 pts (29%). Reported oncologists’ reasons for 2L choice were: change of mechanism of action compared to first line (28%), response to previous TKI (21.2%), intolerance to TKI (17.6%), previous toxicity (12.9%), tumor burden (11.2%), age of the patient (4.1%). Median OS and PFS in 2L were 28.4 and 6.6 mos for N, 16.8 and 6.6 mos for 2L C. Median OS and PFS in 3L were 27 and 5.2 mos for N, 16.6 and 7.5 mos for C. 46 pts received the sequence of drugs N > C, 12 the opposite sequence C > N. Median OS for N > C vs C > N were 96.6 vs 36 mos (p > 0.0001); median PFS for both the sequences were similar at 5.7 mos (p = ns). The cost per patient of the sequence N > C is 51.606 € while for the sequence C > N is 31.480,00 €. Between the two sequences a cost effectiveness per month of survival analysis was performed: the cost per month of OS for the sequence N > C was 534,18 € while for the sequence C > N was 874,46 €, heavily higher. Conclusions: In our real-world setting cohort, most of the pts received N as 2L treatment and a minority received C. Outcome of single drug are superimposable to published literature. With the limits of the retrospective nature of the study, with a cost per month of OS lower a much longer OS, the sequence N > C appear to be a better treatment strategy.
Evaluation of germline genetic testing criteria in early-onset kidney cancer.
Authors: Truong Hong , Sheikh Rania , Kotecha Ritesh , Kemel Yelena , Khurram Aliya , Reisz Peter , Lenis Andrew Thomas , Joseph Vijai , Mandelker Diana , Lee Chung-Han , Feldman Darren R. , Voss Martin H , Coleman Jonathan , Russo Paul , Stadler Zsofia Kinga , Hakimi A. Ari , Motzer Robert J. , Offit Kenneth , Patil Sujata , Carlo Maria Isabel 
Published: March 2021

296 Background: An estimated 5% of kidney cancers are associated with hereditary RCC syndromes. Current germline genetic testing guidelines for patients with kidney cancer were developed to identify carriers of known RCC-associated genes and have evolved in the panel-testing era. We evaluated the utility of the recent National Comprehensive Cancer Network (NCCN) recommendation of testing all patients with early-onset RCC (defined as age of diagnosis ≤ 46 years) for germline variants in genes implicated in hereditary RCC syndromes. Methods: We retrospectively identified patients with RCC diagnosed at age ≤ 46 years who underwent targeted germline testing at our institution through referral to clinical genetics service (n = 68, 29%) or through broad germline testing of ≥77 cancer susceptibility genes using next generation sequencing as part of a prospective matched tumor-normal genomic profiling initiative (n = 165, 71%). Diagnostic performance of referral criteria was assessed by the presence of pathogenic/likely pathogenic (P/LP) germline variants in RCC-associated genes and incidental cancer susceptibility genes. Results: Of 233 patients, 61% were male, 74% were Caucasian, 15% had family history of RCC, 15% had RCC-syndromic features, including 9% with multifocal renal tumors. Most patients (54%) had clear cell RCC (ccRCC). P/LP germline variants were identified in 42 (18%) patients but only 21 (9%) had mutations in RCC genes (12 FH, 4 VHL, 2 SDHB, 1 each in BAP1, TSC1, and FLCN). All 21 early-onset patients with germline variants in an RCC-associated gene also had one of the following risk factors: non-ccRCC histology, family history, or syndromic features. In 91 patients (39%) with a non-RCC germline variants or no alteration, none of these three risk factors were found. Of 21 patients with non-RCC P/LP germline variants, 9 had mutations in moderate/high penetrance genes ( BRCA1 [2], ATM [2], CHEK2 [1], TP53 [2] , PALB2 [1], and RET [1]); 8/9 (89%) met standard criteria for testing for those genes independent of early-onset RCC diagnosis. Conclusions: Patients with early-onset clear cell RCC and no suspicious personal or family history are unlikely to have an RCC-associated germline mutation. RCC-gene panel testing has highest utility in early-onset patients with either non-ccRCC histology, family history of RCC, or RCC-associated syndromic features. Given the high frequency of non-RCC P/LP variants, early-onset RCC patients should be counseled regarding broader testing beyond RCC-associated genes.
Efficacy of avelumab plus axitinib (A + Ax) versus sunitinib (S) by number of IMDC risk factors and tumor sites at baseline in advanced renal cell carcinoma (aRCC): Extended follow-up results from JAVELIN Renal 101.
Authors: Tomita Yoshihiko , Motzer Robert J. , Choueiri Toni K. , Rini Brian I. , Miyake Hideaki , Oya Mototsugu , Albiges Laurence , Fujii Yosuke , Umeyama Yoshiko , Wang Jing , Di Pietro Alessandra , Schmidinger Manuela 
Published: March 2021

302 Background: In the phase III JAVELIN Renal 101 trial (NCT02684006), A + Ax demonstrated progression-free survival (PFS) and objective response rate (ORR) benefit across IMDC risk groups (favorable, intermediate, and poor) vs S in patients with previously untreated aRCC. Here we report efficacy of A + Ax vs S by number of IMDC risk factors (0, 1, 2, 3, and 4-6) and target tumor sites (1, 2, 3, and ≥4) at baseline from the second interim analysis of overall survival (OS). Methods: Patients were randomized 1:1 to receive A 10 mg/kg intravenously every 2 wk + Ax 5 mg orally twice daily or S 50 mg orally once daily for 4 wk (6-wk cycle). PFS and ORR per independent central review (RECIST 1.1) and OS were assessed. Results: At data cut-off (Jan 2019), median (m) follow-up for OS and PFS was 19.3 vs 19.2 mo and 16.8 vs 15.2 mo for the A + Ax vs S arm, respectively. The table shows OS, PFS, and ORR by number of IMDC risk factors and target tumor sites at baseline. A + Ax generally demonstrated efficacy benefit vs S across subgroups. Conclusions: With extended follow-up, A + Ax generally demonstrated efficacy benefit vs S across the number of IMDC risk factors and tumor sites at baseline in aRCC. OS was still immature; follow-up for the final analysis is ongoing. Clinical trial information: NCT02684006 . [Table: see text]
The efficacy of bevacizumab plus erlotinib (B+E) in patients (pts) with renal medullary carcinoma (RMC).
Authors: Wiele Andrew James , Surasi Devaki Shilpa , Rao Priya , Sircar Kanishka , Bathala Tharakeswara , Shah Amishi Yogesh , Jonasch Eric , Cataldo Vince David , Genovese Giannicola , Karam Jose A. , Wood Christopher G. , Tannir Nizar M. , Msaouel Pavlos 
Published: March 2021

303 Background: RMC is a rare and highly aggressive malignancy with a median overall survival (OS) of only 13 months from diagnosis. RMC is thought to be completely refractory to the targeted therapies used against clear cell renal cell carcinoma and the recommended standard of care therapy is platinum-based cytotoxic chemotherapy, which only produces a best response rate of 29% in the first line setting (Shah et al. BJU Int., 2017). Comprehensive molecular profiling of RMC tissues revealed a decrease in genes related to the tricarboxylic acid (TCA) cycle and oxidative phosphorylation and an increase in genes involved in fatty acid synthesis, demonstrating a reliance on aerobic glycolysis to meet cellular bioenergetics needs (Msaouel et al. Cancer Cell, 2020). The combination of B+E is particularly effective in tumors such as fumarate hydratate – deficient renal cell carcinomas, which also rely on aerobic glycolysis. We therefore hypothesized that B+E would show clinical efficacy against RMC. Methods: We analyzed 10 pts with RMC treated with B+E at our institution. A blinded board-certified radiologist reviewed all restaging images to assess best radiographic response as defined by RECIST v1.1 and, when applicable, date of progression. Adverse events (AEs) were evaluated using the CTCAE version 5.0 grading estimated from chart documentation. Clinical-grade next generation genome sequencing for gene mutations, copy number alterations and fusions was performed in 6/10 pts using the Oncomine platform. Results: Between 05/2005 and 09/2020, we identified 10 pts with RMC that were treated with B+E (Table). B+E produced a partial response in 2/10 pts (20%) and stable disease as best response in 6/10 pts (60%), resulting in a median progression-free survival of 3.5 months (mo) with 95% CI 1.8 – 5.2 mo. Decrease in tumor burden was noted even in patients that had received 3+ prior therapies and irrespective of genomic alterations. The median overall survival (OS) from B+E initiation was 7.3 mo (95% CI 5.4 – 9.1) and the median OS from diagnosis was 20.8 mo (95% CI 15.4 – 26.1). B+E was well tolerated with no grade ≥ 4 AEs and only one grade 3 AE (skin rash). Dose reduction was only needed in 1/10 pts. Conclusions: B+E is clinically active and well tolerated in heavily pre-treated pts with RMC and is therefore a viable therapeutic option for this lethal disease. However, pts ultimately relapse and further investigation is needed to elucidate mechanisms of resistance and determine how to optimally target metabolic vulnerabilities in RMC. [Table: see text]
Activity and safety of cabozantinib (cabo) in brain metastases (BM) from metastatic renal cell carcinoma (mRCC): An international multicenter study.
Authors: Hirsch Laure , Martinez Chanza Nieves , Farah Subrina , Flippot Ronan , Rathi Nityam , Collier Katharine , de Velasco Guillermo , Seront Emmanuel , Beuselinck Benoit , Xu Wenxin , Bowman Isaac Alexander , Lam Elaine Tat , Dzimitrowicz Hannah Elizabeth , Zakharia Yousef , McKay Rana R. , Bilen Mehmet Asim , Albiges Laurence , Xie Wanling , Harshman Lauren C , Choueiri Toni K. 
Published: March 2021

310 Background: Cabo shows robust clinical activity in mRCC. Patients (pts) with BM have been underrepresented in clinical trials and effective systemic therapy is lacking. We retrospectively characterized the clinical activity and toxicity of cabo in pts with BM from RCC. Methods: Consecutive medical records from mRCC pts with BM treated with cabo monotherapy across 15 institutions were reviewed. Pts were grouped by radiologic presence (cohort 1) or absence (cohort 2) of progressing intracranial metastases. Brain-directed local therapy was allowed but radiological confirmation of intracranial progression at cabo start was required in cohort 1. Radiological response rate was investigator-assessed by modified RECIST 1.1 for intracranial and RECIST 1.1 for extracranial responses. Time to treatment failure (TTF) and overall survival (OS) were estimated by Kaplan-Meier. Results: We identified 69 pts with BM from RCC, 25 (36%) in cohort 1 and 44 (64%) in cohort 2. Majority were IMDC intermediate/poor (87%) and received cabo as ≥2nd line (75%). Median time from mRCC diagnosis to BM was 19.1 months (mos) (IQR 4.4-39.5). Overall, median number of BM was 3 (range 1-27) and median size of largest lesion was 1.2 cm (range 0.2-6.6) with frontal (62%) and parietal (48%) as the most frequent localizations. Prior brain directed therapy was used in 65% and 93% of pts in cohort 1 and 2 respectively. Median follow-up after cabo initiation was 11 mos (range 4-72). Twenty three percent of pts remained on therapy while 52% discontinued for progression and 9% for toxicity. Intracranial response rate was 61% (95%CI 39%-80%), with 3 complete responses, for cohort 1 and 57% (95%CI 41%-72%) for cohort 2. Only 10% (n = 7) had intracranial progression as best response. For cohort 1, extracranial response was 52% (95%CI 31%-72%), median TTF was 9.9 mos (95%CI 5.9-14.0) and OS was 14.7 mos (95%CI 7.7-23.0). For cohort 2, extracranial response was 41% (95%CI 26%-57%), TTF was 9.0 mos (95%CI 4.6-11.4) and OS was 14.1 mos (95%CI 11.0-22.0). Most common adverse events were fatigue (77%) and diarrhea (46%). Eight pts received concomitant brain-directed treatment during cabo therapy without neurological toxicities. Conclusions: Cabo shows significant intracranial activity and acceptable safety profile in pts with BM from RCC. [Table: see text]
A pilot study of preoperative nivolumab in high-risk nonmetastatic renal cell carcinoma.
Authors: Carlo Maria Isabel , Attalla Kyrollis , Patil Sujata , Murray Samuel J. , Chen Ying-Bei , Kotecha Ritesh , Durack Jeremy C. , Motzer Robert J. , Hakimi A. Ari , Voss Martin H 
Published: March 2021

323 Background: Immunotherapy improves survival in patients with advanced renal cell carcinoma (RCC), but has no established role for perioperative use in patients with localized RCC. Neoadjuvant immunotherapy is a promising strategy in several cancers, and may leverage the primary tumor as antigen source. Methods: We conducted a single institution pilot study of neoadjuvant nivolumab in patients with RCC undergoing nephrectomy with curative intent. Patients were eligible if their risk of metastatic recurrence within the first 12 years was >20% by an established nomogram. After confirmatory biopsy and renal MRI, patients were treated with standard dose nivolumab every 2 weeks for 4 treatments, with a follow-up renal MRI prior to nephrectomy. The primary end points of the study were safety and feasibility defined as being able to complete 3/4 treatments without surgical delay. We evaluated adverse events by CTCAE, surgical safety by Clavien-Dindo classification, and tumor radiographic response by RECIST 1.1. Results: Eighteen (11 men, 7 women; median age 60) were enrolled. All patients had clear cell RCC, median tumor size at baseline was 8.8cm (range 6.4-14.2cm). Median predicted 12-year probability of recurrence was 45% (range 25-71%). All received at least 1 dose of nivolumab; 16/18 patients completed all 4 doses. 17/18 (94%) patients completed at least 3 doses. No patient had notable delay in the timing of their nephrectomy. 4 patients had surgical complications per Clavien-Dindo classification, including 2 with grade 3a chylous ascites after lymphadenectomy. Two patients had nivolumab discontinued for immune-related adverse events, including grade 3 transaminitis and grade 2 arthralgias; a third patient developed grade 4 colitis 4 months after completing nivolumab. All patients had stable disease as the best response prior to surgery. Recurrence-free survival at 2 years was 0.74 (95%CI 0.45-0.90). We analyzed an additional 21 patients with metastatic RCC (20 ccRCC, 1 epithelioid AML) who subsequently had nephrectomy after standard immunotherapy. 15 patients had received ipilimumab+nivolumab, 6 received single-agent PD-1 or PD-L1 inhibitors. 3 (14%) patients achieved a near or complete pathologic response, including a patient with epithelioid AML. Analysis of radiologic and pathologic biomarkers of response are ongoing and will be presented at conference. Conclusions: In this pilot study, there were no new safety signals or delays in surgery with preoperative nivolumab. Neoadjuvant immunotherapy shows preliminary evidence of safety, feasibility and efficacy; biomarker studies may help identify individuals who may have a higher likelihood of response. Clinical trial information: NCT02595918 .