bluuebunny/crossref_metadata_2025_split huggingface dataset:
Real-world outcomes in patients (pts) with metastatic urothelial carcinoma (mUC) who received first- or second-line immunotherapies (IO) in the United States (US).
Authors: Boyd Marley , Annavarapu Srinivas , Doshi Gurjyot K. , Imai Kentaro , Sbar Eric , Godwin James Luke , Li Haojie , Sonpavde Guru 
Published: February 2020

457 Background: Benefit of IO (PD1 and PD-L1 inhibitors) for mUC was observed in clinical trials but real-world evidence for benefit and clinical outcomes is limited. Methods: This was a retrospective study of adult pts with mUC who initiated IO regardless of PD-L1 expression in the first- (1L cohort) or second-line (2L cohort) setting between 5/1/2016-1/31/2019 in the US Oncology Network (USON), a network of community oncology practices. Descriptive and Kaplan-Meier analyses to evaluate baseline characteristics, treatment patterns and clinical outcomes were conducted using data from USON’s electronic heath record. Results: Among 393 pts in the 1L cohort, median (range) age at IO initiation was 77 (42, 90+), 74% were male, 69% were White, and 19.1% and 4.1% had ECOG performance status (PS) 2 and 3/4, respectively. Among the 366 pts in the 2L cohort, median (range) age at IO initiation was 70 (29, 90+), 74% were male, 71% were White, and 19.7% and 1.4% had ECOG PS 2 and 3, respectively. Median (range) follow-up durations from IO initiation were 4.2 (0, 34.1; 1L cohort) and 4.1 (0, 31.3; 2L cohort) months (mo), during which time 43.1% (1L cohort) and 44.4% (2L cohort) of pts died. Median overall survival (OS) from IO initiation (95% confidence interval [CI]) was 10.6 (9.7, 13.2) mo for the 1L cohort and 9.4 (7.1, 11.5) mo for the 2L cohort; 1-year survival probabilities (95% CI) were 46.6% (40.1%, 52.8%; 1L cohort) and 43.4% (36.8%, 49.8%; 2L cohort). By the end of the follow-up, 48.1% of 1L pts and 47.8% of 2L pts were alive and did not advance to next line of therapy, and 13.5% of 1L and 13.4% of 2L cohort pts advanced to the next line of therapy. Median (95% CI) treatment durations were 2.6 (2.1, 2.9) and 2.8 (2.2, 3.5) mo for the 1L and 2L cohorts, respectively; 6-mo ongoing treatment probabilities (95% CI) were 26.6% (22.2%, 31.2%; 1L cohort) and 31.4% (26.4%, 36.4%; 2L cohort). Conclusions: OS of pts in the real world receiving 1L and 2L IO appears consistent with clinical trial results, although survival follow-up is limited. A minority of pts received post-IO therapy. Future research should examine influence of pt characteristics and PD-L1 expression on treatment choice and outcomes.
Real-world outcomes in patients with locally advanced or metastatic urothelial carcinoma receiving taxane monotherapy following platinum and anti-PD-1/L1 therapy.
Authors: Hepp Zsolt , Shah Sonali , Tan Katherine , Balakrishna Shreya 
Published: February 2020

458 Background: There are currently limited options for patients with locally advanced or metastatic urothelial carcinoma (la/mUC) following progression on platinum chemotherapy and anti-programmed death 1/death-ligand 1 (PD-1/L1) therapy. Further, limited data are available from clinical trials or real-world studies on outcomes in this population. This retrospective analysis investigated clinical outcomes in patients treated with taxane monotherapy, a commonly used and NCCN guideline-recommended option in this setting. Methods: Patients aged ≥18 years with histologically-confirmed diagnosis of la/mUC on or after 2011, ≥2 clinical visits, and sufficient relevant unstructured data were included from the de-identified nationwide Flatiron Health electronic health record-derived database. The study cohort included patients treated with taxane monotherapy (docetaxel, paclitaxel, or nab-paclitaxel) following anti-PD-1/L1 therapy and who have received prior platinum containing chemotherapy. Baseline characteristics, overall survival (OS), real-world progression-free survival (rwPFS) based on clinician documentation of disease status, and real-world response (rwR) based on clinician-confirmed radiologic assessments were reported. Patients were followed until death, data cutoff, or loss to follow up. Results: Among 276 patients treated following anti-PD-1/L1 therapy and who met all of the inclusion/exclusion criteria, 72 were treated with taxanes and also had documented prior platinum chemotherapy. Patients were mostly male (75%) and Caucasian (74%), with a mean age of 73 years. 65% had > 2 sites of metastasis at index (start date of taxane). Post index, median OS = 7.6 months (95% CI 5.2, 14.4) and median rwPFS = 2.9 months (95% CI, 2.4, 4.0). Among the 50 patients with ≥1 rwR assessment, confirmed rwR = 18% (95% CI: 9%, 32%). Conclusions: In the real-world setting, limited responses to taxanes and short duration of PFS and OS were observed in patients with la/mUC previously treated with a platinum and anti-PD-1/L1 therapy. There is a need for more effective therapies to improve clinical outcomes for this patient population.
Practice trends and attitudes of medical oncologists on new therapies in urothelial carcinoma.
Authors: Rosenthal Kristen , Galsky Matt D. , Milowsky Matthew I. , Howson Alexandra , Quill Timothy A. , Obholz Kevin 
Published: February 2020

472 Background: Treatment options for patients with metastatic urothelial carcinoma (mUC) have dramatically changed. The goal of this study was to assess the worldwide impact and use of new therapeutic developments in clinical practice. Methods: The study consisted of qualitative telephone interviews (3/25/19-4/5/19) and a quantitative online survey (3/20/19-5/27/19) with questions designed to determine current practice trends and specific challenges faced by clinicians. Participants were recruited via email and answers were compared with those of experts and guideline recommendations. Results: A total of 30 US-based clinicians completed the interviews and 491 participants (US, n = 156; ex-US, n = 335) completed the online survey. Most participants (69%) treated ≤ 10 patients with UC per month. For newly diagnosed mUC, many participants failed to select appropriate first-line therapy based on creatinine clearance (CrCl) and PD-L1 expression (Table). Only 58% of clinicians correctly selected SoC cisplatin-based chemotherapy for eligible patients based on CrCl. For cisplatin-ineligible patients, 60% of clinicians indicated use of an immune checkpoint inhibitor (ICI) despite low PD-L1 expression. Many clinicians were also unfamiliar with novel agents. Only 56% recognized the mechanism of action (MoA) of erdafitinib, an FGFR inhibitor approved during the survey period, and 31% recognized the MoA of enfortumab vedotin, an investigational agent with FDA breakthrough therapy designation. About 40% of US clinicians and < 20% of ex-US clinicians indicated confidence to use these agents in clinical practice if available. Conclusions: This study highlights the need for ongoing education on the optimal use of novel therapeutic strategies to care for patients with mUC. [Table: see text]
Relationship between hyperphosphatemia with infigratinib (BGJ398) and efficacy in FGFR3-altered advanced/metastatic urothelial carcinoma (aUC).
Authors: Lyou Yung , Grivas Petros , Rosenberg Jonathan E. , Hoffman-Censits Jean H. , Quinn David I. , Petrylak Daniel Peter , Galsky Matt D. , Vaishampayan Ulka N. , De Giorgi Ugo , Gupta Sumati , Burris Howard A. , Rearden Jessica , Ye Yining , Wang Hao , Moran Susan , Daneshmand Siamak , Bajorin Dean F. , Pal Sumanta K. 
Published: February 2020

576 Background: Infigratinib (BGJ398) is a potent and selective FGFR1–3 inhibitor with significant clinical activity in aUC bearing FGFR3 alterations. A common adverse event is hyperphosphatemia, a class effect associated with FGFR1 inhibition. We sought to better understand the relationship between hyperphosphatemia and response to infigratinib in patients with aUC. Methods: Eligible patients had aUC with activating FGFR3 mutations/fusions and had received prior platinum-based chemotherapy, unless contraindicated. Patients received infigratinib 125 mg orally daily (3w on/1w off) until disease progression or unacceptable toxicity. Calcium and phosphate levels within normal limits were required at enrollment. Efficacy was assessed by overall response rate (ORR) and disease control rate (DCR) based on RECIST 1.0 criteria. All patients received prophylaxis with the oral phosphate binder sevelamer. Hyperphosphatemia was defined as serum phosphorous >5.5 mg/dL, consistent with the threshold for action in the protocol. Results: Of the 67 patients enrolled, 48 (71.6%) had hyperphosphatemia on ≥1 post-baseline lab test. Efficacy findings in patients with vs without hyperphosphatemia were: ORR 33.3% (95% CI 20.4–48.4) vs 5.3% (95% CI 0.1–26.0), mPFS 4.9 months (95% CI 3.65–5.98) vs 1.84 months (95% CI 1.28–3.48), and mOS 8.74 months (95% CI 5.72–13.67) vs 7.62 months (95% CI 2.53–15.57). Median treatment length was 4.1 vs 1.4 months and mDOR was 5.0 vs 3.7 months for patients with vs without hyperphosphatemia, respectively. A landmark analysis at the 1-month mark was performed, and hyperphosphatemia (Y/N) was determined based on lab tests within the first month. The differences in efficacy outcomes were still observed. Conclusions: Hyperphosphatemia is a well-described class effect and pharmacodynamic biomarker of FGFR inhibitors, including infigratinib, and is generally reversible/easily managed with diet and phosphate binders. Our data support prior observations with FGFR inhibitors, suggesting that hyperphosphatemia is associated with treatment response and is not negatively associated with treatment length. Clinical trial information: NCT01004224.
Combination of dual immune checkpoint inhibition (ICI) with stereotactic radiation (SBRT) in metastatic renal cell carcinoma (mRCC) (RADVAX RCC).
Authors: Hammers Hans J. , Vonmerveldt Dendra , Ahn Chul , Nadal Rosa Maria , Drake Charles G. , Folkert Michael Ryan , Laine Aaron Michael , Courtney Kevin Dale , Brugarolas James , Song Daniel Y. , Hannan Raquibul , Carducci Michael Anthony 
Published: February 2020

614 Background: Dual ICI with nivolumab/ipilimumab (N/I) has become a standard of care (SOC) for patients (pts) with mRCC. Since the failure to respond to ICI may be due to a lack of immune recognition, novel vaccination approaches and stimulation of the innate immune system (e.g. stimulator of interferon genes (STING) agonists) are being pursued in clinical trials. Because preclinical studies using SBRT have demonstrated the a.) release of tumor antigens, b.) STING pathway activation and c.) synergy with ICI, we have conducted a study to explore the safety and efficacy of this approach in mRCC pts. Methods: Pts with clear cell mRCC were screened and enrolled at two sites (UT Southwestern and Johns Hopkins). Prior treatment with tyrosine kinase inhibitors (TKI) and IL2 were allowed. Enrolled pts received standard of care dosing with Nivolumab (3 mg/kg) and Ipilimumab (1mg/kg) IV q3weeks followed by nivolumab monotherapy. SBRT was administered to 1-2 disease sites with a dose of 50 Gy in 5 fractions between the first and the second dose of N/I. The primary goals of this exploratory study were to determine the safety and tolerability as well as the objective response rate (ORR) by RECIST 1.1 of non-irradiated lesions. Results: A total of 29 pts were screened and 25 pts were enrolled. 11 (44%) of pts received at least one prior systemic therapy: 4 (16%) pts received IL2 and 7 (28%) TKI therapy. The cohort was primarily intermediate and poor risk pts (favorable risk n = 2 (8%), intermediate risk n = 20 (80%), poor risk n = 3 (12%)). 10 (40%) pts required immune suppressive therapy with prednisone for classic immune related adverse events as seen with dual ICI. Radiation pneumonitis limited to the radiation field (grade 2) was seen in 2 pts and responded promptly to oral steroids. At the time of analysis, partial responses (PR) were observed in 14/25 patients with an ORR of 56%. Additional analyses including duration of response, progression free survival and overall survival will be presented. Conclusions: Dual ICI with SBRT showed an acceptable safety and encouraging antitumor activity in mRCC warranting further investigations. Clinical trial information: NCT03065179.
Tivozanib as first-line treatment of metastatic renal cell carcinoma: A real-world outcome review in North-West of England, United Kingdom.
Authors: Wong Sam , Prasad Kellati , Waddell Tom , Charnley Natalie , Wong Helen , Law Andrea , Parikh Omi , Pillai Manon , Griffiths Richard , Chow Shien 
Published: February 2020

638 Background: Tivozanib is a selective tyrosine kinase inhibitor (TKI) of vascular endothelial growth factor and has been shown to offer PFS and tolerance advantage compared to sorafenib among patients with mRCC. In this retrospective review, we aim to investigate the real world efficacy and tolerance of tivozanib delivered in four cancer hospital in the Northwest of England. Methods: mRCC patients started tivozanib in first line setting were identified and reviewed. Primary outcomes of interest include overall response rate (ORR), survival (OS, PFS where possible) and treatment tolerance. Results: A total of 113 patients were identified between March 2017 and May 2019. Median follow up was 200 days (15-792). 26% were switched from other prior TKI due to intolerance. 28%, 48% and 24% had Favourable (F), Intermediate (I) and Poor(P) IMDC risk category respectively. ORR was 29% (CR 0%, PR29%, SD38%, PD26%, NE 7%). Median PFS (after 53 events) was 9 months (F = NR, I = 7 months, P = 3 months p value < 0.0001) with estimated 6 and 12 months OS of 80% and 67 % respectively. At cut-off, 26/32 with F IMDC risk remaining on treatment c.f. 24/54 (I) and 6/27 (P). Median treatment received was 5 cycles and 65% still on full dose at end of observation. Dose reduction was necessary in 31% while treatment was stopped in 15% due to toxicity. 46% received subsequent therapy post- progression. The commonest adverse events were fatigue (32%, G3 0%), diarrhoea (15%, G3 1.7%), mucositis (15%, G3 < 1%), and anorexia (7%, G3 1.7%). Conclusions: Preliminary findings from this review suggests similar clinical efficacy of tivozanib compared to agents such as pazopanib or sunitinib in real-world setting particularly among patient with Favourable IMDC category however longer follow up is required to fully evaluate this. Treatment is well tolerated with low incidence of severe grade toxicities and may be a good monotherapy option in patient of Favourable IMDC category unsuitable for combination therapies.
Real-world evidence of cabozantinib in metastatic renal-cell carcinoma (mRCC): Results from the Canadian Kidney Cancer Information System (CKCis).
Authors: Zhang Hanbo , Basappa Naveen S. , Joy Isaiah , Ghosh Sunita , Lalani Aly-Khan A. , Hansen Aaron Richard , Heng Daniel Yick Chin , Castonguay Vincent , Kollmannsberger Christian K. , Winquist Eric , Wood Lori , Bjarnason Georg A. , Breau Rodney H. , Pouliot Frederic , Kapoor Anil , Graham Jeffrey 
Published: February 2020

682 Background: Cabozantinib is a multitargeted tyrosine kinase inhibitor (TKI) that has demonstrated efficacy in mRCC randomized trials. Less is known about the activity of cabozantinib in patients (pts) exposed to immuno-oncology (IO) agents. We explored the real-world effectiveness of cabozantinib, including in pts who had progressed on IO therapy. Methods: Using CKCis, a prospective Canadian database, pts treated with cabozantinib monotherapy as second-line or later were identified. Baseline clinical and treatment characteristics were collected. Rates of partial response (PR), stable disease (SD), progressive disease (PD) and disease control (DCR, PR+SD) were determined along with median time to treatment failure (mTTF) and median overall survival (mOS). Results: A total of 156 pts were identified. Median age was 62 years (range 21-84), 74% of pts had clear-cell histology, and 54% had > 3 sites of metastases (12% in CNS, 47% in bone). At time of cabozantinib start, 34% had KPS score < 80. Outcomes are described below. Conclusions: The effectiveness of cabozantinib observed in this real-world population was consistent with results from clinical trials. Cabozantinib also appears to provide benefit to mRCC pts who have progressed on prior IO therapy, and should be incorporated into contemporary treatment algorithms. Further follow up is ongoing.[Table: see text]
Development of a predictive model of PSA response to a switch from prednisone to dexamethasone in metastatic castrate-resistant prostate cancer patients biochemically progressing on abiraterone.
Authors: Barua Reeta , Phillips Cameron , Arciero Vanessa Sarah , Zhang Liying , Rahmadian Amanda , Delos Santos Seanthel , Parshad Shruti , Emmenegger Urban 
Published: February 2020

88 Background: Abiraterone acetate (AA) is typically administered with prednisone (P) to prevent symptoms of mineralocorticoid excess in patients with metastatic castrate resistant prostate cancer (mCRPC). After biochemical progression on AA + P, there is a sizeable subset of patients who have a renewed PSA response when switched from P to dexamethasone (D). The purpose of this study was to delineate clinical and pathologic factors that are predictive of a PSA response to such a steroid switch. Methods: We performed a retrospective analysis of 87 patients switched from AA+P to AA+D at Sunnybrook Odette Cancer Centre (Toronto, ON, Canada) between December 2012 and September 2018. Information on demographics, disease characteristics, previous treatments and performance status was collected. Response to the P to D switch maneuver was defined as a decrease in PSA by ≥30% within 12 weeks of the intervention (PSA30). Univariate logistic regression analyses were used to create a prediction model for each covariate tested, and R2 was applied for the measure of fit.Using multivariable logistic regression analysis and a backward stepwise selection procedure, we sought to identify patient and/or disease characteristics associated with a PSA30. Results: 38/87 patients (44%) experienced a PSA30. Univariate analysis showed that a favourable ECOG performance status, no prior docetaxel and no prior enzalutamide use were associated with a PSA30. On multivariable logistic regression analysis both favourable ECOG performance status and no prior enzalutamide use remained associated with a PSA30 (Table). Conclusions: A considerable proportionof patients with mCRPC who biochemically progress on AA+P have a renewed PSA response when changed to AA+D.Patients with a favourable ECOG performance status and no prior enzalutamide use are more likely to respond to such a steroid switch. Further prospective studies are needed to validate our findings.[Table: see text]
A multicenter phase IIb trial to evaluate the efficacy and tolerability of ModraDoc006/r in subjects with metastatic castration-resistant prostate cancer (mCRPC), suitable for treatment with a taxane (NCT04028388).
Authors: Vaishampayan Ulka N. , De Wit Edwin J. , Shore Neal D. , Dreicer Robert , George Daniel J. , Boccia Ralph V. , Curti Brendan D. , Geczi Lajos , Csõszi Tibor , Vogelzang Nicholas J. 
Published: February 2020

TPS268 Background: Docetaxel IV and prednisone is a standard of care in mCRPC with demonstrated overall survival benefit. ModraDoc006 is a novel oral tablet formulation of docetaxel and to enhance bioavailability, it is co-administered with ritonavir (/r), an inhibitor of cytochrome p450 3A4 and P-glycoprotein. The oral combination, denoted as ModraDoc006/r, could be preferable due to patient convenience and elimination of infusion reactions and prophylactic steroids administration. Due to its weekly administration and exposure levels, increased efficacy may be demonstrated. Methods: The study is an open label 1:1 randomized phase 2b trial of ModraDoc006/r bi-daily QW versus docetaxel IV 75 mg/m2 Q3W. Thirty (30) mg ModraDoc006 combined with 200 mg /r in morning and 20 mg ModraDoc006 with 100 mg /r in evening is administered on days 1, 8 and 15 of a 21 day cycle. Safety and preliminary efficacy of ModraDoc006/r have been established in a phase Ib trial in mCRPC pts. All patients will receive 5 mg oral prednisone twice daily. Treatment is continued until progression, unacceptable toxicity or patient wish. mCRPC pts with measurable disease per RECIST 1.1, suitable for docetaxel therapy, are eligible. No prior treatment with taxanes is allowed. Primary objective is objective response rate (ORR) as assessed by investigators. Secondary objectives include PSA response, PSA-PFS, time to skeletal related events and progression, duration of response, disease control rate and safety assessments. Patient reported outcomes and health-related quality of life will be captured with treatment satisfaction and FACT-P questionnaires. It is expected that ModraDoc006/r will be at least as effective as docetaxel IV. A sample size of 50 evaluable pts per arm will evaluate an estimated ORR of 25% in each arm, with a 5% two-sided alpha and power of 83.7%. Conclusions: ModraDoc006/r represents an advance in prostate cancer therapeutics with convenience of oral administration, reduced myelosuppressive toxicity and potential improved efficacy over IV docetaxel. Clinical trial information: NCT04028388.
Phase III study of perioperative pembrolizumab (pembro) plus neoadjuvant chemotherapy (chemo) versus placebo plus neoadjuvant chemo in cisplatin-eligible patients (pts) with muscle-invasive bladder cancer (MIBC): KEYNOTE-866.
Authors: Siefker-Radtke Arlene O. , Steinberg Gary D. , Bedke Jens , Nishiyama Hiroyuki , Fang Xiao , Kataria Ritesh , Homet Moreno Blanca , Hoimes Christopher J. 
Published: February 2020

TPS599 Background: MIBC prognosis is poor, despite standard neoadjuvant cisplatin-based chemo. PD-1/PD-L1 pathway inhibition is an effective first-line option for cisplatin-ineligible pts and a second-line option for platinum-based chemo pretreated pts. Neoadjuvant chemo + pembro, a PD-1 inhibitor, recently showed encouraging pathologic complete response rates, in cisplatin-eligible patients with MIBC (NCT02365766), warranting further investigation. Methods: KEYNOTE-866 (NCT03924856) is a randomized phase 3 study to assess efficacy and safety of chemo+perioperative pembro versus chemo+perioperative placebo for pts with MIBC. An estimated 790 patients will be randomly assigned 1:1 to neoadjuvant pembro+chemo (4 cycles) followed by adjuvant pembro after radical cystectomy+pelvic lymph node dissection (RC+PLND, 13 cycles) or neoadjuvant placebo+chemo (4 cycles) followed by adjuvant placebo after RC+PLND (13 cycles). Pts will receive neoadjuvant and adjuvant pembro 200 mg IV Q3W; neoadjuvant chemo will be gemcitabine 1000 mg/m2+cisplatin 70 mg/m2 IV Q3W. Pts will be stratified by tumor PD-L1 status (combined positive score [CPS] ≥10 vs CPS <10), disease stage (T2 vs T3/4), and region of treatment (Unites States vs Europe vs most of world). Adults (≥18 y) with histologically confirmed MIBC (T2-T4aN0M0) who are cisplatin-eligible, are clinically nonmetastatic (N0M0), and have an ECOG PS 0 or 1 will be enrolled. Pts are required to provide tumor tissue for histology and PD-L1 analysis. Pts will not be permitted to have previously received systemic antineoplastic treatment for MIBC or radiotherapy to the bladder. Imaging by CT/MRI will be performed Q12W for up to 96 wk after cystectomy, at discontinuation, and during follow-up starting at 3 y (Q24W). Primary end points are pathologic complete response and event-free survival in all pts and pts with PD-L1 CPS ≥10. Secondary end points are OS, disease-free survival, and pathologic downstaging rate in all pts and pts with PD-L1 CPS ≥10, and safety. Accrual began June 13, 2019. Clinical trial information: NCT03924856.