bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characterizing patterns of disease progression in patients with genitourinary cancers treated with immune checkpoint inhibitors.
Authors: Patel Vaibhav G. , Qin Qian , Mellgard George , Parikh Anish B. , Wang Bo , Alerasool Parissa , Garcia Philip , Jaladanki Suraj , Leiter Amanda , Carroll Emily , Brooks Danielle , Shimol Jennifer Ben , Eisenberg Elliot , Gallagher Emily J. , Galsky Matt D. , Oh William K. , Tsao Che-Kai 
Published: February 2020

482 Background: Despite the widespread use of immune checkpoint inhibitors (ICIs), patterns of disease progression (POD) are poorly characterized. We aim to define these characteristics in patients (pts) with advanced urothelial carcinoma (UC) and renal cell carcinoma (RCC) treated with ICIs. Methods: We retrospectively reviewed charts of pts with advanced UC and RCC who received at least 2 ICI doses at our institution from 12/1/10 – 10/31/18. Demographics, medical history, ICI course, toxicity, and outcomes were recorded. Characteristics at the time of radiographic POD including location of metastases (mets), symptoms (sx), and hospitalization details were collected. Fisher’s exact test was used to study differences in pts with and without hospitalization at POD. Results: Of the 71 pts identified (UC N=53; RCC N=18), 59 pts had POD. At POD, 19 (32.2%) pts had new sites of disease involvement, while the remaining pts (N=40, 67.8%) had progression only at previously known sites of disease. Fourty-six (78.0%) pts had sx at POD: 1 sx (N=19, 32.2%), 2 sx (N=13, 22.0%), 3+ sx (N=14, 23.7%). Pain was the most common sx at POD (N=32, 54.2%), followed by loss of energy (N=18, 30.5%), and loss of appetite (N=14, 23.7%). Twenty-five (42.4%) pts were hospitalized at POD, most commonly for sepsis (N=8, 32%). No clinical factors were identified to predict for pts being hospitalized at POD. Conclusions: In our review of GU cancer patients on ICIs, a large proportion of pts reported clinical sx at POD, pain being the most frequent. Furthermore, a substantial number of pts were hospitalized at POD, most commonly for sepsis. Thus, further studies are warranted to confirm these findings, and potentially identify strategies to optimize patients’ quality-of-life and reduce rates of hospitalizations at the time of POD on ICIs.
Outcomes of patients with high-risk non-muscle invasive bladder cancer (NMIBC) who undergo radical cystectomy after BCG and subsequent salvage intravesical therapy.
Authors: Packiam Vignesh T. , Labbate Craig V. , Boorjian Stephen A. , Tarrell Robert F. , Adamic Brittany , Mahmoud Mohammad , Tsivian Matvey , Avulova Svetlana , Cheville John , Karnes R. Jeffrey , Tollefson Matthew K. , Werntz Ryan P. , Steinberg Gary D. , Frank Igor 
Published: February 2020

483 Background: We evaluate the impact of salvage intravesical therapy on survival in patients with NMIBC previously treated with BCG who ultimately underwent radical cystectomy (RC). Methods: We retrospectively identified patients with NMIBC who received at least 1 complete induction course of BCG and subsequently underwent RC for bladder cancer between 2000-2018. Patients were stratified by receipt of salvage intravesical therapy following BCG prior to RC. Oncologic outcomes were compared using Cox proportional hazards regression analysis and the Kaplan-Meier method. Results: We identified 371 patients who underwent RC after receiving BCG, of whom 55 (15%) received salvage intravesical therapy, most commonly Mitomycin C (n = 26), Valrubicin (n = 8), Gemcitabine (n = 7), and CG0070 (n = 6). Median follow-up among survivors was 1.1 (IQR 0-4.3) years. Patients who received salvage intravesical therapy were more likely to initially present with CIS (27% vs 17%) and less likely to present with T1 disease (33% vs 50%, both p < 0.05). Receipt of salvage intravesical therapy was not associated with increased risk of adverse pathology (≥pT2 or pN+) at RC (33% vs 41%, p = 0.27). Furthermore, on Kaplan-Meier analysis, receipt of salvage intravesical therapy was not associated with cancer-specific or overall survival. On multivariable Cox proportional hazards regression, clinical stage prior to RC, but not receipt of salvage intravesical therapy, was associated with inferior cancer-specific survival and overall survival. Conclusions: Our results suggest that RC following carefully managed salvage intravesical therapy after BCG is not associated with inferior oncologic outcomes, which can improve patient counseling. [Table: see text]
FORT-1: Phase II/III study of rogaratinib versus chemotherapy (CT) in patients (pts) with locally advanced or metastatic urothelial carcinoma (UC) selected based on FGFR1/3 mRNA expression.
Authors: Quinn David I. , Petrylak Daniel Peter , Bellmunt Joaquim , Necchi Andrea , Gurney Howard , Lee Jae-Lyun , Van Der Heijden Michiel Simon , Rosenbaum Eli , Penel Nicolas , Pang See-Tong , Li Jian-Ri , Garcia del Muro Xavier , Joly Florence , Papai Zsuzsanna , Ellinghaus Peter , Lu Chengxing , Nakajima Keiko , Ishida Tatiane , Nishiyama Hiroyuki , Sternberg Cora N. 
Published: February 2020

489 Background: Aberrant activation of fibroblast growth receptor (FGFR) signaling plays a role in UC. Rogaratinib, a pan-FGFR1-4 inhibitor, has promising efficacy and safety in pts with advanced muscle-invasive UC, selected based on FGFR1-3 mRNA overexpression and/or FGFR3-activating mutations/translocations. This Phase II/III, randomized, open-label study evaluated the efficacy of rogaratinib vs CT in pts with FGFR-positive advanced or metastatic UC who received prior platinum CT. We present an ORR analysis for rogaratinib vs CT. Methods: FGFR1/3 mRNA was tested by in situ hybridization of archival tissue. Pts were randomized 1:1 to 800 mg rogaratinib p.o. BID continuously or CT Q3W (i.v., docetaxel 75 mg/m2, paclitaxel 175 mg/m2, or vinflunine 320 mg/m2), and stratified by PIK3CA/ RAS-activating mutations, prior immunotherapy, and modified 4-factor Bellmunt risk score. Results: 87 pts were assigned to rogaratinib and 88 to CT. Overall, 82.9% were male, median age was 69.0 yrs (range: 36-89), 96.6% had stage IV disease, and 2.3% were stage IIIB. PIK3CA/ RAS-activating mutations were present in 11.4% of pts. ORRs of 19.5% and 19.3% (1-sided p=0.56) and disease control rates of 49.4% and 55.7% (p=0.84) were observed for rogaratinib and CT, respectively; median progression-free survival was 2.7 months (95% CI 1.6, 4.2) and 2.9 months (95% CI 2.6, 4.2). Grade 3-4 treatment-emergent adverse events occurred in 40/86 pts (47%) treated with rogaratinib and 46/82 pts (56%) with CT, most commonly anemia (3% vs 15%), neutropenia (1% vs 17%), asthenia (9% vs 1%), lipase increase (8% vs 2%), fatigue (2% vs 6%), and urinary tract infection (2% vs 6%). Exploratory analysis of pts with FGFR3 DNA alterations (4 spot mutations and fusions) showed ORRs of 52.4% with rogaratinib and 26.7% with CT. Conclusions: In pts with FGFR1/3 tumor mRNA-positive UC, rogaratinib had efficacy comparable with standard CT and an acceptable safety profile. Subgroup analysis suggests rogaratinib may be more active in pts with an FGFR3 DNA alteration. Sensitivity analysis of biomarker subgroups is ongoing. Clinical trial information: NCT03410693.
Clinical criteria predicting an overall survival benefit to platinum rechallenge (PR) in metastatic urothelial cancer (mUC).
Authors: Mussat Elodie , Jouinot Anne , Saldana Carolina , Joly Charlotte , Allory Yves , Nourieh Maya , Vordos Dimitri , Salomon Laurent , de la TAILLE Alexandre , Tournigand Christophe , Rousseau Benoit 
Published: February 2020

490 Background: In mUC, 2nd line treatments after platinum-based regimen have limited efficacy, such as vinca-alkaloid, taxan or immune checkpoint inhibitors. PR is proposed by ESMO guidelines if progression occurs >12 months after initial exposure with low level of evidence. Our objectives were to assess if PR was associated with better outcomes compared to other regimens and to identify parameters predicting its benefit in mUC. Methods: From a large monocentric cohort of mUC pts pretreated by 1st line platinum-based regimen, we retrospectively included pts who received a second line (PR, other cytotoxic drugs, immunotherapy). The primary end point was overall survival (OS). Survival analyses were performed using Cox models, weighted on a propension score to ensure groups comparability. Results: Among 155 consecutive pts firstly treated between 2006 and 2017, 55 pts were then treated by PR and 45 pts treated by other chemotherapy (n=37), immunotherapy (n=6) or targeted therapy (n=2). As PR is used in pts who benefited from platinum therapy, we restricted the analyses to pts who did not progressed during 1st line, resulting in 43 PR pts and 25 pts treated by other regimens. Univariate analyses identified main factors impairing OS at 2nd line initiation: time from prior chemotherapy <6 months, non-complete response to 1st line treatment and 2nd line treatment without platinum. These factors were subsequently used in a propension score to weigh survival analyses. PR was significantly associated with better OS than other regimens (HR=0.57, CI95% [0.37-0 .88], p=0.011). Median OS, median PFS and ORR were 16.5 vs 9.0 months (P=0.012), 5.8 vs 2.4 months (P=0.012) and 45 vs 15% (P=0.048) for PR and other regimens respectively. The most common grade 3 to 4 adverse events were hematologic toxicities: 54% for PR vs 22% for other treatments. ROC curve analysis of the best delay for PR since the end of 1st line was 5.7 months (sensitivity 60%, specificity 84%). Conclusions: PR is feasible and associated with significant OS improvement in second line treatment of mUC in pts that benefited initially from 1st line platinum and with Platinum-free interval >6 months. These results should be confirmed prospectively.
Interim results of PEANUT: pembrolizumab and nanoparticle albumin-bound paclitaxel (nab-paclitaxel) as salvage therapy for metastatic urothelial carcinoma (UC).
Authors: Necchi Andrea , Raggi Daniele , Bandini Marco , Farè Elena , Giannatempo Patrizia , Colecchia Maurizio , Pederzoli Filippo , Gallina Andrea , Marandino Laura , Calareso Giuseppina , Madison Russell , Briganti Alberto , Ross Jeffrey S. , Montorsi Francesco 
Published: February 2020

494 Background: Pembrolizumab (pembro) is a new standard of care in chemotherapy (CT) pre-treated patients (pts) with metastatic UC. Nab-paclitaxel (nPtx) demonstrated preliminary activity in advanced UC. In the PEANUT study (NCT03464734) we investigate their combination in advanced UC after CT failure. Methods: In an open-label, single-arm, phase 2 trial, pts receive 200 mg pembro, intravenously (IV), on D1 and 125 mg/m2 IV nPtx on D1 and D8, every 3 weeks, until disease progression (PD) or onset of unacceptable toxicity. Key inclusion criteria are: predominant UC histology, failure of ≤2 platinum-based CT for metastatic disease. Response is evaluated by RECIST v.1.1 criteria every 2 cycles. Biomarkers include PD-L1 expression with the combined positive score (CPS) and comprehensive genomic profiling on tumor and blood samples (FoundationONE and FoundationACT assay). The primary endpoint of the study is the progression-free survival (PFS). The target is to detect an improvement in the median PFS from ≤3.0 months (H0) to ≥5.0 months (H1). Results: Between 01 and 08/2019, PEANUT enrolled 46 pts evaluable for the study endpoint: 26% female, median age 66 y (range 43-78); 70% had failed 1 prior systemic therapy vs 30% 2 prior therapies; 24% had ECOG-performance status 1; 28% had liver metastases. The median TMB was 6.9 mut/Mb. After median follow-up of 5 months, 18 pts have relapsed (39%). The projected median PFS was 7 months (95%CI: 4-not achieved). The confirmed objective response-rate (ORR) was 47.8% (95%CI: 32.9-63.1): 18 partial responses and 4 complete responses (8.7%). Grade 3 treatment-related adverse events (TRAE) were seen in 6 pts (13%). Most common any-grade TRAE included alopecia (91%), asthenia (21.7%), and neutropenia (15%). Neither TMB nor CPS were significantly associated with PFS on univariable analyses. 7/8 pts with PI3KCA mutations in matched tumor/blood samples had an objective response (87.5%). Conclusions: Preliminary results from PEANUT study demonstrated a promising PFS and a clinically meaningful ORR in II-III line setting of advanced UC. Updated data, including mature PFS, duration of response and biomarkers will be presented. Clinical trial information: NCT03464734.
The role of previous radical local treatment (RLT) on the outcome of immune checkpoint inhibitors (ICI) in patients (pts) with metastatic urothelial carcinoma (mUC).
Authors: Morales-Barrera Rafael , Vidal Casinello Natalia , Domenech Montserrat , Bonfill Teresa , Puente Javier , Figols Mariona , Joaquin Julia Giner , Gonzalez Macarena , Lozano Fernando , Lopez Hector , Galante Isabel , Mast Richard , Serra Hernandez Ester , Semidey Maria Eugenia , Serrano Cesar , Gallardo Diaz Enrique , Suarez Rodriguez Cristina , Maldonado Xavier , Morote Juan , Carles Joan 
Published: February 2020

496 Background: There is a growing interest in local treatment for metastatic solid tumors. Recently, retrospective studies have reported the potential benefit of RLT to primary bladder cancer in pts with metastatic disease. We tested the impact of previous RLT in pts with mUC treated with ICI. Methods: Data from pts with mUC treated with ICI collected between May 2013 and May 2019 using a multi-institutional database was evaluated. Stratification was made according to previous RLT with ICI versus no RLT with ICI. We defined RLT as radical surgery (RS) or ≥50 Gy of radiotherapy (RT) delivered to the bladder. The X2 test was used to determine differences in rates. Overall survival (OS) between previous RLT plus ICI (group A) versus no RLT plus ICI (group B) generated using Kaplan-Meier method was compared by log-rank test. OS was calculated from the date of initiation of ICI to the date of death. Analyses were performed using SPSS v21. Results: A total of 115 pts with mUC were treated with ICI, 62 (53.9%) previously were treated with RS, 7(6.1%) RT and 46 (40%) no received RLT. ICI prescribed were atezolizumab (55.7%), pembrolizumab (16.5%), durvalumab (11.3%), durvalumab/tremelimumab (7.8%), nivolumab (5.2%) and avelumab (3.5%). The disease control rate (CR [6.9%] +PR [9.6%] +SD [14.1%]) was higher for pts with previous RLT compared to those pts who did not receive RLT (CR [3.2%] + PR [5.8%] + SD [6.4%](P=0.325). Median OS was 11.23 mo (95% CI; 6.02-16.44) and 7.95 mo (95%IC; 5.15-10.75) for group A and group B, respectively (P=0.481). Conclusions: This multicenter cohort suggests that previous RLT might play an impact for control disease in pts with mUC treated with ICI. Although this is hypothesis generating, the true value of this approach remains to be demonstrated in prospective studies.
The efficacy of two cycles of neoadjuvant chemotherapy for upper tract urothelial carcinoma patients.
Authors: Zennami Kenji , Takahara Kiyoshi , Fukaya Kosuke , Ichino Manabu , Fukami Naohiko , Sasaki Hitomi , Sumitomo Makoto , Kusaka Mamoru , Shiroki Ryoichi 
Published: February 2020

505 Background: Upper tract urothelial carcinoma (UTUC) is frequently upstaged after surgery and is associated with poor prognosis. However, the efficacy of neoadjuvant chemotherapy (NAC) and optimal No. of NAC cycles for UTUC have been poorly defined. In this study, we evaluated if two cycles of NAC improves survival of UTUC patients in our institute. Methods: A total of 167 patients who underwent radical nephroureterectomy at Fujita Health University between November 2005 and December 2018 were retrospectively analyzed. The study group comprised 114 patients with UTUC who received NAC followed by surgery. The control group consisted of 53 patients who underwent initial surgery without NAC. We compared two groups in overall survival (OS), cancer specific survival (CSS), recurrence free survival (RFS, urinary tract, visceral) and independent prognostic factors. Kaplan-Meier methods, log-rank test and cox proportional-hazards models were used for statistical analysis. Results: Median follow up was 1108 days, and there were no significant differences in preoperative patient characteristics between NAC group and initial surgery (IS) group. NAC had significantly improved 5-year OS (75% vs 55%, p=0.004) and 5-year CSS (84% vs 65%, p=0.024). That is more significant in the analysis with cT3 patients (p=0.0002). NAC also significantly improved visceral RFS (p=0.001). However, NAC does not affect urinary tract RFS (p=0.96) when compared to IS. pDS were observed in 55 out of 114 (48%) in NAC group, and 12 out of 53 (22%) in IS group. Comparison of OS between with pDS and without pDS demonstrated significantly better OS in with pDS group (p=0.0001). Multivariate cox proportional-hazards models identified NAC, pDS, resection margin, pN and cT3 as independent prognostic factors for OS. Conclusions: Two cycles of NAC induced pDS and improved survival of UTUC patients. Reduced number of NAC cycles may offer clinical benefits of low chemo-associated toxicity, appropriate surgery without delay in chemo-resistant case and sufficient cancer regression with pDS.
Prospective trial of adjuvant chemotherapy versus adjuvant radiation therapy for locally advanced bladder cancer after radical cystectomy.
Authors: Zaghloul Mohamed S. , Christodouleas John Paul , Zaghloul Tarek , Smith Andrew , Abdalla Ahmed , Khaled Hussein Mustafa , William Hany , Hwang Wei-Ting , Baumann Brian Christopher 
Published: February 2020

515 Background: Some chemotherapy-naïve patients with locally advanced bladder cancer (LABC) after radical cystectomy (RC) are sufficiently de-conditioned that they are not candidates for adjuvant chemo or decline it. Adjuvant radiotherapy (RT) is an alternative (or complementary) adjuvant therapy, but is rarely performed, with most of these patients being observed. In a prospective trial, we compared RT vs adjuvant chemo & hypothesized that RT can achieve comparable disease-free survival (DFS). Methods: A randomized phase III trial at the National Cancer Institute (Cairo) compared adjuvant RT (standard of care in Egypt) vs. chemo+RT after RC for LABC. A 3rd arm, adjuvant chemo, was added later (gemcitabine/cisplatin x 4). Herein, we report results of RT vs adjuvant chemo. Patients ≤70 y/o with ≥1 of the following (pT3b/T4a, grade 3 or pN+) with negative margins after RC were eligible. RT was delivered with 3-D conformal RT to the pelvis (45 Gy in 1.5 Gy BID). Routine follow-up & pelvic CT q 6 months were performed. Post hoc non-inferiority exploratory analysis was performed. Results: 123 were enrolled (78 RT/45 chemo). 51% had urothelial carcinoma; 49% had squamous cell carcinoma. The arms were well-balanced except for gender (p=0.06). Two-year outcomes & overall adjusted hazard ratios (HR) for RT vs chemo were 54% vs 47% for DFS [HR 0.65(95%CI 0.35-1.19, p=0.16]; 92% vs 69% for local-regional recurrence-free survival [HR 0.28(95%CI 0.10-0.82), p=0.02]; 75% vs 79% for distant metastasis-free survival [HR 2.39(95%CI 0.94-6.09), p=0.07]; 61% vs 60% for overall survival [HR 0.94(95%CI 0.52-1.69), p=0.83]. In the urothelial cohort, there were no differences in DFS or OS. Late grade ≥3 GI toxicity was observed in 6 RT patients (8%) & 1 chemo patient (2%). Based on our data, there is a >90% probability that the true difference in 2-year DFS is <10%, the prespecified non-inferiority margin. Conclusions: This prospective study demonstrates that adjuvant RT has superior local control vs adjuvant chemo with no statistically significant differences in DFS or OS. Results suggest that RT can be an option for patients with LABC after RC where an alternative to chemo is desired by the patient or physician. Clinical trial information: NCT01734798.
Alvimopan as an essential component of ERAS protocol to decrease length of hospital stay.
Authors: Hanna Peter , Kalapara Arveen , Regmi Subodh , Srujana Kalyana , Zabell Joseph , Randle Darrel , Kaizer Alexander , Patten Luke , Konety Badrinath R. , Wahr Joyce , Weight Christopher J. 
Published: February 2020

517 Background: Radical cystectomy for muscle invasive bladder cancer is the gold standard. However, it is frequently associated with a prolonged length of hospital stay (LOS). We study the effect of ERAS protocol implementations and Alvimopan use in patients undergoing radical cystectomy and its impact on length of hospital stay (LOS). Methods: Retrospective cohort study involving consecutive patients undergoing radical cystectomy for bladder cancer at our institution from 2010 through 2018. We evaluated Alvimopan use plus an ERAS protocol post radical cystectomy versus patients who underwent ERAS protocol alone versus those who were managed prior to ERAS protocol implementation. Primary outcome of interest was LOS, controlling for age, sex, smoking status and Charleson comorbidities index. Results: 146 patients (49.32 %) received standard care (non-ERAS) (group A), 102 patients (34.45 %) underwent ERAS protocol alone (group B) and 47 patients (15.87 %) underwent ERAS protocol plus Alvimopan (group C). There was no significant difference in length of stay between group A and group B (p=0.856). However, group C experienced a shorter LOS (16.6%) compared to group A (p=0.015). Similarly, group B was not significantly associated with the days to bowel movements compared to group A (p=0.112), however, group C demonstrated a significantly shorter time (16.3%) to bowel movements compared to group A (p=0.015). On other hand, group c wasn’t significantly associated with time tolerance to regular diet (p=0.068). Limitations include retrospective nature of some of the data, non-randomized approach and confounders such as a mix of robot and open approaches to cystectomy. Conclusions: Of all ERAS protocol components, Alvimopan appeared to be the most significant contributor in accelerating GI recovery and decrease LOS in our cohort.
Response to salvage chemotherapy after progression on immune checkpoint inhibitors in patients with advanced urothelial carcinoma.
Authors: Beom Seung-Hoon , Rha Sun Young , Ahn Joong Bae , Shin Sang Joon 
Published: February 2020

519 Background: Immune checkpoint inhibitors (ICI) are active in patients with advanced urothelial carcinoma which progressed to platinum-based chemotherapy. Recent data suggest that exposure to ICI improves response to salvage chemotherapy (SCT) in several cancer types. Here we evaluated whether PD-1/PD-L1 inhibitors affect the antitumor effects of SCT after ICI in patients with urothelial carcinoma. Methods: A retrospective study was conducted at Yonsei Cancer Center. Eligibility criteria were patients who received at least one SCT as 3rd-line or beyond, following progression after platinum-based chemotherapy and ICI and for whom efficacy data were available between January 2017 and September 2019. We evaluated efficacy outcomes to each therapy, including ORR by RECIST version 1.1, progression-free survival (PFS), and overall survival (OS). Results: In total, 35 patients met the inclusion criteria and were included in the analyses. ICIs were given as monotherapy and they were administrated as second-line in 48% and as later line in 52%. Twenty-six patients (74%) received a anti-PD-L1 inhibitor and 9 (26%) did a anti-PD-1 inhibitor. SCT included single paclitaxel (60%), MVAC (26%), gemcitabine/platinum combination (9%), and pemetrexed (6%). The ORR to SCT was 26%. Among 9 patients who received MVAC, 5 (55.5%) achieved a partial response. Median progression-free survival was 2.5 months and median overall survival was 7.8 months. A number of prior chemotherapy regimens was associated with response to SCT on univariate analysis. Conclusions: In urothelial cancer patients, the confirmed ORR (26%) to SCT after ICI exposure was higher as compared to historical data from the pre-ICI era. These data indicate that anti–PD-1/PD-L1 inhibitors could make tumors more vulnerable to subsequent chemotherapy.