bluuebunny/crossref_metadata_2025_split huggingface dataset:
IMmotion150: A phase II trial in untreated metastatic renal cell carcinoma (mRCC) patients (pts) of atezolizumab (atezo) and bevacizumab (bev) vs and following atezo or sunitinib (sun).
Authors: Atkins Michael B. , McDermott David F. , Powles Thomas , Motzer Robert J. , Rini Brian I. , Fong Lawrence , Joseph Richard Wayne , Pal Sumanta K. , Sznol Mario , Hainsworth John D. , Stadler Walter Michael , Hutson Thomas E. , Ravaud Alain , Bracarda Sergio , Suarez Cristina , Choueiri Toni K. , Qiu Jiaheng , Huseni Mahrukh A. , Schiff Christina , Escudier Bernard J. 
Published: September 2018

4505 Background: While inhibiting VEGF improves outcomes in mRCC pts, most develop resistance, often within a year. Here, we report results from a Ph II study of atezo (anti–PD-L1) and bev (anti-VEGF) vs and following atezo or sun (TKI) in mRCC pts. Methods: Pts with untreated mRCC were enrolled in the hypothesis generating IMmotion150 study (NCT01984242) and randomized to atezo 1200 mg IV q3w + bev 15 mg/kg IV q3w, atezo alone or sun 50 mg PO QD 4 wk on/2 wk off. After progression on atezo or sun, crossover to atezo + bev was allowed. PD-L1 status was scored on tumor-infiltrating immune cells (IC, SP142 IHC assay). The primary analysis was modified prior to final analysis to reflect the coprimary endpoints of IRF-assessed PFS (RECIST v1.1) in ITT pts and pts with PD-L1 expression on ≥ 1% of IC (PD-L1+). Results: 54% of pts were PD-L1+. In PD-L1+ pts 1L treatment resulted in a PFS hazard ratio (HR) of 0.64 for atezo + bev vs sun (table). After 1L treatment, 78% of sun and 60% of atezo pts who progressed subsequently received atezo + bev and achieved ORRs of 28% and 24%, respectively (table). Safety was comparable to the known individual profiles of atezo and bev. Additional clinical, safety and biomarker data will be presented. Conclusions: Atezo + bev resulted in encouraging antitumor activity in 1L pts with PD-L1+ mRCC. Preliminary activity in the 2L setting was demonstrated in pts who crossed over to atezo + bev, regardless of prior therapy. 1L atezo + bev vs sun is being evaluated in the ongoing Ph III study IMmotion151 (NCT02420821). Clinical trial information: NCT01984242. [Table: see text]
A phase I/II study to assess the safety and efficacy of pazopanib (PAZ) and pembrolizumab (PEM) in patients (pts) with advanced renal cell carcinoma (aRCC).
Authors: Chowdhury Simon , McDermott David F. , Voss Martin Henner , Hawkins Robert E. , Aimone Paola , Voi Maurizio , Isabelle Naëije , Wu Yi , Infante Jeffrey R. 
Published: September 2018

4506 Background: PAZ is indicated for the treatment of aRCC. The combination of an anti-angiogenic agent and immunotherapy may improve anti-tumor activity. We report preliminary safety and efficacy results of the phase I part of the study. Methods: Twenty pts were originally enrolled in cohorts A and B assessing PAZ 800 mg and 600 mg, respectively, both with 2mg/kg (Q2W and then Q3W) PEM to determine the maximum tolerated dose. Due to dose limiting liver toxicity, cohort C was opened to assess if the sequential schedule of 9 weeks PAZ run-in followed by PAZ+PEM would improve safety. Strict safety criteria for initiating PAZ+PEM were set. The data from this ongoing study are presented given the limited information available on the combination of TKI + PD-1 inhibitors in RCC. Results: Overall, 35 pts were treated; 5 out of 15 pts in cohort C received PAZ+PEM at the data cut-off. Three dose-limiting toxicities (DLT) occurred in cohort C in pts receiving PAZ+PEM; updated DLTs in all cohorts are reported in Table. G3/4 AEs were observed in 90% of pts in cohorts A and B and in 80% of pts in cohort C receiving PAZ+PEM. No G3/4 ALT/AST elevation was reported in cohort C PAZ+PEM while they were observed in 70% and 60% in cohorts A and B, respectively. Best overall response (CR+PR) was reported in 6, 2 and 1 pts receiving PAZ+PEM in cohorts A, B and C, respectively. Conclusions: Results from cohorts A and B showed significant hepatotoxicity. The sequential schedule PAZ → PAZ+PEM has shown reduced hepatotoxicity and preliminary signs of efficacy but overall limited tolerability. PAZ+PEM is not suitable to test in a larger cohort. Clinical trial information: 2013-003785-14. [Table: see text]
Epacadostat plus pembrolizumab in patients with advanced RCC: Preliminary phase I/II results from ECHO-202/KEYNOTE-037.
Authors: Lara Primo , Bauer Todd Michael , Hamid Omid , Smith David C. , Gajewski Thomas , Gangadhar Tara C. , Somer Bradley G. , Schmidt Emmett V. , Zhao Yufan , Gowda Hema , Olszanski Anthony J. 
Published: September 2018

4515 Background: Epacadostat (E) is a potent oral inhibitor of indoleamine 2,3-dioxygenase 1 (IDO1), a tryptophan-catabolizing enzyme that induces immune tolerance by T-cell suppression. Preclinical and clinical data suggest that epacadostat has antitumor activity when combined with checkpoint inhibitors, including the PD-1 inhibitor pembrolizumab (P). ECHO-202/KEYNOTE-037 is an ongoing open-label, phase 1/2 (P1/2) study evaluating E + P in multiple tumor types. We report preliminary P1/2 efficacy and safety data for the advanced renal cell carcinoma (RCC) cohort as of a 29OCT2016 data cutoff. Methods: Eligible patients (pts) had advanced clear-cell RCC, prior antiangiogenic therapy (tx), and no prior checkpoint inhibitor tx. In P1 dose escalation (3+3+3), pts received E (25, 50, 100, or 300 mg PO BID) + P (2 mg/kg or 200 mg IV Q3W); MTD was not exceeded. E (100 mg BID) + P (200 mg Q3W) dosing was selected for P2 cohort expansion. Response was assessed in RECIST 1.1 evaluable pts. Safety/tolerability was assessed in pts receiving ≥1 E + P dose. Results: 33 pts (P1, n = 11; P2, n = 22) were enrolled (median age, 63 years; 70% men; 97% white; MSKCC criteria of favorable, intermediate, and poor in 6%, 64%, and 12% of pts, respectively). Of 30 efficacy-evaluable pts, 63% (n = 19) had 0–1 prior tx and 37% (n = 11) had ≥2 prior tx for advanced disease. ORR (CR+PR) and DCR (CR+PR+SD) for pts with 0–1 prior tx was 47% (9/19; 1 CR, 8 PR) and 58% (11/19; 1 CR, 8 PR, 2 SD), respectively; for pts with ≥2 prior tx, ORR and DCR were 0% and 36% (4/11; all SD). At data cutoff, 9/9 responses were ongoing (range, 1+ to 372+ days). PFS and biomarker analyses are ongoing. TRAEs occurring in ≥10% of the 33 pts included fatigue and rash (36% each); and arthralgia, diarrhea, pruritus, and pyrexia (12% each). Grade ≥3 TRAEs occurred in 15% of pts (none in > 1 pt). Two pts discontinued due to TRAEs (grade 3 autoimmune hepatitis, n = 1; grade 3 aseptic meningitis/headache/nausea/vomiting/anxiety, n = 1). Conclusions: E + P was generally well tolerated and associated with encouraging response outcomes in advanced RCC pts with 0–1 prior line of tx. E + P represents a novel immunotherapeutic strategy. A phase 3 RCC study is planned. Clinical trial information: NCT02178722.
Updated efficacy and safety of avelumab in metastatic urothelial carcinoma (mUC): Pooled analysis from 2 cohorts of the phase 1b Javelin solid tumor study.
Authors: Apolo Andrea B. , Ellerton John Allan , Infante Jeffrey R. , Agrawal Manish , Gordon Michael S. , Aljumaily Raid , Britten Carolyn D. , Dirix Luc Yves , Lee Keun-Wook , Taylor Matthew H. , Schöffski Patrick , Wang Ding , Ravaud Alain , Gelb Arnold , Xiong Junyuan , Rosen Galit , Patel Manish R. 
Published: September 2018

4528 Background: Avelumab, a fully human anti‒PD-L1 IgG1 antibody, has shown promising efficacy and safety in 2 cohorts of patients (pts) with mUC. We now report updated data from a pooled analysis of these pts with mUC from JAVELIN Solid Tumor (NCT01772004) and further characterize the clinical activity of avelumab in this disease. Methods: Pts with mUC progressed after platinum-based therapy or cisplatin ineligible received avelumab 10 mg/kg 1-hour IV Q2W. Tumors were assessed every 6 weeks by independent review (RECIST v1.1). Endpoints included objective response rate (ORR), duration of response (DOR), progression-free survival (PFS), overall survival (OS), safety (NCI CTCAE v4.0), and tumor PD-L1 expression. Results: As of Jun 9, 2016, 249 pts had received avelumab for a median of 12 weeks (range 2-92) and were followed up for a minimum of 6 weeks. Primary tumor site was upper tract (renal pelvis/ureter) in 23.3% and lower tract (bladder/urethra) in 76.7%. 242 pts (97.2%) had progressed on prior platinum therapy and 7 pts (2.8%) were platinum naive. In 161 post-platinum pts with ≥6 months of follow-up, confirmed ORR was 17.4% (95% CI 11.9-24.1; complete response in 6.2%) with a disease control rate of 39.8%. Response was ongoing in 23/28 responders at data cut (82.1%; median DOR not reached), and the 24-week durable response rate was 92.3% (95% CI 72.6-98.0). Responses occurred across PD-L1 expression levels tested (≥5% and < 5% tumor cell‒staining [25.4% and 13.2%]). In all post-platinum pts (n = 242), median PFS was 6.6 weeks (95% CI 6.1-11.6), median OS was 7.4 months (95% CI 5.7-10.3) and 6-month OS rate was 54.9 (95% CI 47.7-61.7). Treatment-related adverse events (TRAE) of any grade occurred in 166/249 pts (66.7%); most common (≥10%) were infusion-related reaction (22.9%, all grade ≤2) and fatigue (16.1%). 21 pts (8.4%) had a grade ≥3 TRAE (fatigue [1.6%] and asthenia [0.8%] in > 1 pt). 34 pts (13.7%) had an immune-related AE (grade ≥3 in 2.4%). There was 1 treatment-related death (pneumonitis). Conclusions: Avelumab was well tolerated and showed durable responses in heavily pretreated pts with mUC, irrespective of tumor PD-L1 expression status. Clinical trial information: NCT01772004.
Health-related quality of life (HRQoL) of pembrolizumab (pembro) vs chemotherapy (chemo) for previously treated advanced urothelial cancer (UC) in KEYNOTE-045.
Authors: De Wit Ronald , Bajorin Dean F. , Bellmunt Joaquim , Fradet Yves , Lee Jae-Lyun , Fong Lawrence , Vogelzang Nicholas J. , Climent Miguel Ángel , Petrylak Daniel Peter , Choueiri Toni K. , Necchi Andrea , Gerritsen Winald R. , Gurney Howard , Quinn David I. , Culine Stephane , Sternberg Cora N. , Mai Yabing , Li Haojie , Perini Rodolfo F. , Vaughn David J. 
Published: September 2018

4530 Background: In KEYNOTE-045 (NCT02256436) (N = 542), pembro 200 mg Q3W significantly improved OS over investigator’s choice of paclitaxel, docetaxel, or vinflunine as second-line therapy for advanced UC following platinum-based chemo (HR 0.73; P = 0.0022). Fewer treatment-related AEs were reported with pembro. We present results of the prespecified HRQoL analysis of KEYNOTE-045. Methods: The EORTC QLQ-C30 HRQoL instrument was administered electronically at cycles 1–4, then every 2 cycles for up to 1 y and 30 d after discontinuation. The key HRQoL end points were 1) change from baseline to wk 15 and 2) time to deterioration (TTD) (defined as ≥10-point decrease from baseline) in the QLQ-C30 global health status/QoL score. HRQoL was assessed in patients (pts) who received ≥1 dose of assigned study treatment and completed ≥1 HRQoL instrument (N = 520). Score change from baseline was compared using a constrained longitudinal data analysis model. TTD was compared using a stratified log-rank test and Cox proportional hazards model. Results: Baseline global health status/QoL scores were similar between arms. HRQoL compliance at wk 15 was 88% for both arms. From baseline to wk 15, scores were stable for pembro (n = 266) (least squares [LS] mean +0.75 [95% CI –2.34 to +3.83]) but worsened for chemo (n = 254) (LS mean –8.30 [95% CI –11.76 to –4.83]); the difference in LS means between arms was 9.05 (95% CI 4.61-13.48; nominal 2-sided P < 0.001). At wk 15, pts without PD had improved scores with pembro but worsened scores with chemo (LS mean +5.97 vs –4.31), while pts with PD had less worsening with pembro (LS mean –3.54 vs –13.95). TTD was prolonged with pembro (HR 0.70; 95% CI 0.55-0.90; nominal 1-sided P = 0.002; median 3.5 mo vs 2.2 mo). Rates of improvement (defined as ≥10-point increase from baseline) at wk 15 were 31.2% with pembro and 22.0% with chemo; rates of deterioration were 28.9% and 40.6%, respectively. Conclusions: Pembro was associated with substantially better HRQoL for a longer duration than investigator-choice chemo in pts with previously treated advanced UC. Along with superior OS, these data support pembro as a new standard-of-care in this population. Clinical trial information: NCT02256436.
Predictors of urinary diversion choice in patients with bladder cancer in integrated care settings.
Authors: Kwan Marilyn L. , Leo Michael C , Lee Valerie S. , Danforth Kim N. , Weinmann Sheila , O'Keeffe-Rosetti Maureen Cecelia , Yi David , Wendel Christopher S. , Bulkley Joanna E. , Hornbrook Mark C. , Krouse Robert S. , Gilbert Scott Michael , McMullen Carmit K. 
Published: September 2018

4543 Background: Annually over 10,000 people with bladder cancer in the US have cystectomy surgery with urinary diversion (UD). While ileal conduit (IC) is most common, neobladder (NB) and continent pouch (CP) are options to retain urinary continence. Few studies in community settings have examined patient and clinician factors associated with UD choice. Methods: Eligible patients were age ≥21 with a cystectomy and UD for bladder cancer from 1/2010 to 6/2015 in 3 West coast Kaiser Permanente regions. Data were obtained from the EHR and chart review.We useda mixed effects logistic regression model with surgeon as a random effect, and region as a fixed effect, to identify patient factors associated with UD choice (IC vs NB/CP). We also examined whether surgeon factors were associated with UD choice above and beyond patient factors. Results: Among 1063 patients, 80% had an IC. IC patients were older (mean age 72 vs. 62), more likely female (24% vs. 16%), more likely diagnosed with AJCC stage III/IV (41% vs. 28%), and had higher Charlson comorbidity score (median 4 vs. 3) than NB/CP patients. Surgeons accounted for a sizable portion of the variability in UD choice (ICC = .26). The model with patient factors showed good fit (AUC = .93, Hosmer-Lemeshow test p = .22). Including surgeon factors (annual cystectomy volume, specialty training, clinical tenure) did not improve model fit (p = .32). Female sex, eGFR < 45, 4+ comorbidities, and stage III/IV tumors were associated with higher odds of receiving an IC vs. NB/CP (Table). Conclusions: Patient factors predict much of the variability in UD choice. The high ICC indicates that surgeons also contribute to this process, but surgeon factors we examined were not uniquely associated with IC. Future studies should explore more nuanced surgeon factors, such as how UD choice is shaped by personal beliefs about UD and likely outcomes. [Table: see text]
Inter and intra-tumor heterogeneity of PD-L1 and MET expression in metastatic renal cell carcinoma (mRCC).
Authors: Derosa Lisa , Le Teuff Gwenael , Khordahi Manal , Chanez Brice , Zalcman Emanuelle , Gravis Gwenaelle , Negrier Sylvie , Radulescu Camelia , Albiges Laurence , Merabet Zahira , Escudier Bernard J. 
Published: September 2018

4569 Background: Although inhibition of PD-1/PD-L1 and MET receptors have clinical efficacy in mRCC, their expression is not a predictive biomarker. Heterogeneity between the sites of disease might be one explanation. The aim of our study was to evaluate PD-L1 and MET expression in primary and metastases (brain (BM)/pancreas (PM)) RCC lesions and their correlation with clinicopathologic characteristics. Methods: RCC specimen from different institutions were collected. Clinicopathologic characteristics were assessed by revision of samples. PD-L1 and MET expression in tumor cells (TC) and immune cells (IC) ( > 1%) were assessed by immunohistochemistry. Results: 180resected RCC specimen were successful collected (42 primary tumors and 138 metastases (87 BM/51 PM)). Overall, 22%, 51% and 23% of patients had at least one specimen expressing PD-L1 TC, IC and MET, respectively. In primary tumours, the proportion was 12%, 50% and 0%, respectively. In metastasis, the proportion of PD-L1 TC was 22% (23% in BM vs 19% in PM, p = 0.631), PD-L1 IC was 48% (47% in BM vs 49% in PM, p = 0.821) and MET was 24% (35% in BM vs 2% in PM, p < 0.001). Comparing paired samples (primary tumour and metastasis) there was discordances of PD-L1 in TC or IC and of MET expression in 30%, 27% and 24% of samples, respectively. These two first disagreements seem varied over time. The discordance in PD-L1 TC or IC and MET between primary tumor and PM (BM) was 15% (40%), 33% (22%) and 0% (67%), respectively. Some correlations were observed between MET and PD-L1 and clinicopathologic characteristics. Conclusions: In this largest analysis, evaluating heterogeneity between primary tumor and metastases (brain/pancreatic lesions) in mRCC, PD-L1 and MET expression suggests that the assessment as predictive biomarkers may require analysis of metastatic lesions. [Table: see text]
Nivolumab treatment for patients with non-clear cell renal cell carcinoma: A multicenter retrospective analysis.
Authors: Koshkin Vadim S. , Barata Pedro C. , Vogelzang Nicholas J. , Pal Sumanta K. , Hsu Joann , Allman Kimberly D , Gilligan Timothy D. , Rini Brian I. 
Published: September 2018

4586 Background: Nivolumab (Nivo) is approved for metastatic renal cell carcinoma (mRCC) refractory to prior antiangiogenic therapy. However, the clinical activity of Nivo in non-clear cell RCC subtypes remains unknown as these patients were not part of the trial population. Methods: Patients (pts) from 3 centers who received at least one dose of Nivo as monotherapy for mRCC between 12/2015 and 01/2017 were identified. All patients had histologically-confirmed non-clear cell histology. A retrospective analysis focusing on patient and treatment characteristics, objective response according to RECIST v1.1 and adverse events (AEs) was undertaken. Results: Twenty-three patients were identified. Median age was 59 years (33-82), 78% were male, 61% were white, 30% black and 9% Hispanic. MSKCC risk groups were 19% favorable, 67% intermediate, 14% poor. Most common histologies were Unclassified (48%) and Papillary (44%), followed by Collecting duct and Mucinous tubular and spindle cell carcinoma (MTSCC) (4% each). The majority of pts had ECOG PS 0 (57%) or 1 (33%). At diagnosis, 65% had metastatic disease; most common sites were lung (57%), retroperitoneal lymph nodes (35%), and liver or bone (26% each). Most pts (74%) had prior nephrectomy and had received one (74%) or > 1 (26%) prior systemic therapy, most commonly sunitinib (65%), pazopanib (30%) or axitinib (17%). No pts had prior IL-2, but one pt had atezolizumab on trial. After a median follow-up of 6.5 months (mos) and 8 Nivo doses, median PFS was 4.2 mos and median OS was not reached. Among 21 pts evaluable for best response, 6 (29%) had PR and 4 (19%) had SD. Median time to best response was 5.1 mos. At the time of analysis, 9 pts were still on Nivo, 2 were on treatment break, 8 pts had subsequent treatment after PD on Nivo, and 2 were lost to follow-up. Two of 23 pts died. Most common AEs ( > 10%, any grade) were fever (13%) and fatigue (13%). Nivo treatments were postponed in 6 pts due to intolerance and stopped in3 pts. There were no treatment-related deaths. Conclusions: Nivolumab monotherapy demonstrated a substantial objective response rate and was well tolerated in a heterogeneous population of treatment-refractory patients who had mRCC with non-clear cell histology.
Development and validation of a novel clinical-genomic risk group classification for prostate cancer incorporating genomic and clinicopathologic risk.
Authors: Spratt Daniel Eidelberg , Zhang Jingbin , Santiago-Jimenez Maria , Davis John W. , Den Robert Benjamin , Dicker Adam , Kane Christopher J. , Pollack Alan , Ross Ashley , du Plessis Marguerite , Choeurng Voleak , Yousefi Kasra , Haddad Zaid , Davicioni Elai , Weinmann Sheila , Schaeffer Edward M. , Klein Eric A. , Karnes R. Jeffrey , Feng Felix Yi-Chung , Nguyen Paul L. 
Published: September 2018

5000 Background: It is clinically challenging to integrate genomic classifier results that report a continuous numerical risk of recurrence into treatment decisions for prostate cancer (PCa). We aimed to develop a novel clinical-genomic risk system that can readily be incorporated into treatment guidelines for localized PCa. Methods: Four multi-center cohorts (n = 6928 men; 5937 prospective samples and 991 retrospective samples with long-term follow-up) were utilized to identify and validate our clinical-genomic risk system in radical prostatectomy (RP) samples and subsequently in pre-treatment biopsy samples. All patients’ FFPE tissue underwent microarray analysis, and the expression values for 22 prespecified biomarkers that constitute Decipher were extracted. Cumulative incidence curves were constructed to estimate metastasis risk. C-indices were calculated to compare NCCN and CAPRA score to our clinical-genomic system. Results: With a median follow-up of 8 years for men in our RP cohort, the 10-year distant metastasis rates for NCCN low, favorable-intermediate, unfavorable-intermediate, and high-risk were 7.8%, 9.4%, 40.1%, and 41.4%, respectively. Our 3-tier clinical-genomic risk groups had 10-year distant metastasis rates of 3.7%, 30.7%, and 57.7%, for low, intermediate, and high-risk, which were validated in our pre-treatment biopsy cohort with 10-year rate of distant metastasis of 0%, 30.3%, and 63.2%, respectively. C-indices for the clinical-genomic system (0.84, 95%CI 0.62-0.92) were significantly improved over NCCN (0.71, 95%CI 0.59-0.84) and CAPRA (0.71, 95%CI 0.60-0.81) score. A total of 33.4% of men would be reclassified by the clinical-genomic system, and specifically 17.1%, 41.3%, and 19.4% of men in NCCN low, intermediate and high risk groups would be reclassified by our new system. Conclusions: The use of a readily available genomic classifier in combination with clinicopathologic variables can generate a simple to use 3-tier clinical-genomic risk system that is highly prognostic for distant metastasis, is more accurate than clinical risk, and can be easily incorporated into NCCN guidelines to inform treatment decisions.