bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pembrolizumab (pembro) versus investigator’s choice of paclitaxel, docetaxel, or vinflunine in recurrent, advanced urothelial cancer (UC): 5-year follow-up from the phase 3 KEYNOTE-045 trial.
Authors: Bellmunt Joaquim , Necchi Andrea , De Wit Ronald , Lee Jae-Lyun , Fong Lawrence , Vogelzang Nicholas J. , Climent Durán Miguel A. , Petrylak Daniel P. , Choueiri Toni K. , Gerritsen Winald R. , Gurney Howard , Quinn David I. , Culine Stephane , Sternberg Cora N. , Xu Jin Zhi , Homet Moreno Blanca , Godwin James Luke , Bajorin Dean F. , Vaughn David J. , Fradet Yves 
Published: June 2021

4532 Background: Pembro was approved for the treatment of locally advanced or metastatic UC that progressed during or after a platinum-containing regimen, based on the phase 3 KEYNOTE-045 (NCT02256436) trial that showed significantly improved OS with use of pembro. Updated results are presented from KEYNOTE-045 after >5 y of follow-up since the last patient (pt) was randomized. Methods: KEYNOTE-045 is a randomized, multisite, open-label, phase 3 trial. Pts with histologically or cytologically confirmed UC, progression after platinum-containing chemo, ECOG PS 0-2, measurable disease per RECIST v1.1, and ≤2 prior lines of systemic therapy were eligible. Pts were randomly assigned 1:1 to receive pembro 200 mg Q3W or investigator’s choice of paclitaxel 175 mg/m2 Q3W, docetaxel 75 mg/m2 Q3W, or vinflunine 320 mg/m2 Q3W. Primary end points are PFS (RECIST v1.1, blinded central review) and OS. ORR and duration of response (DOR) were key secondary end points. Results: As of Oct 1, 2020, among 542 enrolled pts, median time from randomization to data cutoff was 62.9 mo (range 58.6-70.9). 9.4% and 0% of pts in the pembro and chemo arms, respectively, completed 2 years of therapy. Median OS was longer for pembro vs chemo (10.1 vs 7.2 mo; HR, 0.71 [95% CI, 0.59-0.86]) overall and in pts with CPS ≥10 (8.0 vs 4.9 mo; HR, 0.59 [95% CI, 0.40-0.86]). For pts with CR or PR, median OS was not reached and 16.4 (95% CI, 11.3-25.1) mo in the pembro and chemo arms, respectively (Table). OS rates at 48 mo were 16.7% for pembro and 10.1% for chemo; 60-mo OS rates were 14.9% and 8.7%, respectively. OS benefit with pembro vs chemo continued regardless of age, ECOG PS, prior therapy, liver metastases, baseline hemoglobin, time from last chemo, histology, risk factors, and chemo choice. Median DOR for responders was longer for pembro vs chemo (29.7 mo [1.6+ to 60.5+] vs 4.4 mo [1.4+ to 63.1+]), and a greater proportion of responses lasted ≥48 mo (40.9% vs 28.3%, Kaplan-Meier) and ≥60 mo (32.8% vs 28.3%). ORR was higher for pembro vs chemo (21.9% vs 11.0%; difference 10.8% [95% CI, 4.6-17.0]). Fewer pts given pembro vs chemo experienced a treatment-related AE of any grade (62.0% vs 90.6%) or grade ≥3 (16.9% vs 50.2%). Conclusions: After 5 y, pembro maintained clinically meaningful OS benefit vs chemo in pts with locally advanced or metastatic UC that progressed during or after platinum-based chemo. Pts who responded to pembro experienced a durable response (median >2 y). Clinical trial information: NCT02256436 .[Table: see text]
Influence of first-line chemotherapy regimen on survival outcomes of patients with advanced urothelial carcinoma who receive second-line immunotherapy.
Authors: Miron Benjamin , Handorf Elizabeth A. , Zarrabi Kevin , Zibelman Matthew R. , Ghatalia Pooja , Anari Fern , Plimack Elizabeth R. , Geynisman Daniel M. 
Published: June 2021

4535 Background: Treatment of advanced urothelial carcinoma (mUC) has improved following approvals of PD-1/PD-L1 inhibitors. Platinum chemotherapy remains the standard-of-care in the first-line (1L). Cisplatin (Cis) regimens are accepted to be superior to carboplatin (Carbo) regimens for patients (pts) who are Cis-eligible. We sought to evaluate if differences in efficacy of 1L Cis vs. Carbo have meaningful impact on overall survival (OS) in the era of second-line (2L) immunotherapy (IO). Methods: We conducted a retrospective, observational cohort study to compare OS for pts treated with 1L Cis or Carbo combined with gemcitabine (Gem) followed by 2L IO using patient-level data from the nationwide Flatiron Health electronic health record (EHR)-derived de-identified database. Pts included were diagnosed with mUC between 9/1/2015 and 9/15/2020. 2L IO was defined as single-agent atezolizumab, avelumab, durvalumab, nivolumab, or pembrolizumab. OS was calculated from start of 1L and 2L therapy and compared using Kaplan-Meier curves. Time to 2L IO was calculated from start of 1L to start of IO. Adjusted OS was calculated using multivariable Cox regression models, adjusting for age, gender, race, ECOG performance status, primary site, prior cystectomy, smoking status, and year of diagnosis. Results: A total of 1882 pts were included, 924 (49.1%) received Gem/Cis and 958 (50.9%) received Gem/Carbo in 1L. A similar percentage of pts did not receive any 2L therapy following Gem/Cis (46.4%) or Gem/Carbo (46.0%). Our analysis focused on the 780 pts (41.4%) who received 2L IO—381 after Gem/Cis and 399 after Gem/Carbo. Median follow-up time for the group was 35 months (mo). Pts in the Gem/Cis cohort were younger, had better performance status and lower incidence of upper tract disease (Table). OS from start of 1L therapy was numerically longer in pts who received Gem/Cis compared to Gem/Carbo on unadjusted (median 18.0 v 16.2 mo, p = 0.06) and adjusted analyses (HR = 0.83, 95% CI 0.69-1.00, p = 0.055) but neither result was statistically significant. Time to 2L IO was longer for pts receiving Gem/Cis (6.5 mo) vs Gem/Carbo (5.5 mo, p = 0.008). Survival time on 2L IO did not differ significantly by 1L regimen (Gem/Cis 8.0 mo vs Gem/Carbo 8.2 mo p = 0.36). Conclusions: Real world data suggests that in pts with mUC who are able to receive second-line IO, the choice of first-line platinum chemotherapy may not provide a distinguishable OS benefit. Despite methodologic limitations of this data, a greater focus in discussions with patients on toxicity associated with cisplatin vs carboplatin may be warranted.[Table: see text]
Use of neoadjuvant chemotherapy in elderly patients with muscle invasive bladder cancer: A population-based study, 2006 to 2017.
Authors: Posielski Natasza , Jung Nathan , Koenig Hannah , Ho On , Flores John Paul , Porter Christopher 
Published: June 2021

4536 Background: Current guidelines recommend neoadjuvant chemotherapy (NAC) prior to radical cystectomy (RC) for muscle invasive bladder cancer (MIBC). NAC has been shown to confer a survival benefit across all ages. Yet, many elderly patients are not offered NAC due to concern regarding physiologic reserve and postoperative complications. Our objective was to evaluate age-based disparity in treatment and outcomes of MIBC. Methods: Using the National Cancer Database, we identified patients with MIBC from 2006-2017. First, use of different treatments, RC, RC and adjuvant chemotherapy, RC with NAC (“optimal treatment”), chemo-radiation, and no treatment, was compared between age groups. A second analysis was performed in the cohort of elderly patients, ≥70, undergoing cystectomy. Propensity weighting was used to compare peri-operative and mortality outcomes in those who received NAC vs. no NAC. Results: In 70,911 patients with non-metastatic MIBC, use of RC with NAC was lower in patients ≥70, 7.2 vs. 20.9%, p<0.001 (Table). Patients receiving RC with NAC were younger, had private insurance, higher high school completion rate and median income, shorter distance to hospital, lower CCI, diagnosis in recent years, and higher stage disease. NAC use was also associated with pelvic lymph node dissection (OR 4.55, p<0.001). In patients ≥70 undergoing RC, NAC was associated with shorter length of stay (LOS) (8.5 vs 9.6 days, p<0.001), decreased 30-day readmission (8.6 vs 10.6%, p=0.003), lower 30- and 90-day mortality (1.9 vs 3.6%, p=0.01 and 4.9 vs 7.7%, p=0.004, respectively), and better overall survival (OS) (43.8% vs. 37.5%, p<0.001). Multivariate logistic regression found NAC as an independent predictor of shorter LOS, lower 30-and 90-day mortality, and improved OS. Conclusions: Despite increased omission of NAC in patients ≥70, NAC is not associated with worse peri-operative outcomes or mortality in elderly patients. Advanced age in properly selected patients should not preclude offering NAC prior to radical cystectomy.[Table: see text]
Impact of recurrence on health-related quality of life in patients at high risk of recurrence after radical surgery for muscle-invasive urothelial carcinoma (MIUC): Results from the phase 3 CheckMate 274 trial.
Authors: Galsky Matt D. , Witjes Johannes Alfred , Gschwend Jürgen , Braverman Julia , Broughton Edward , Nasroulah Federico , Alhasani Hasan , Maira-Arce Mario , Ye Xiaomei , Shi Ling , Hamilton Melissa , Bajorin Dean F. 
Published: June 2021

4540 Background: Patients (pts) undergoing radical surgery for MIUC face a high risk of disease recurrence. Recurrence is associated with worse survival, but its effect on health-related quality of life (HRQoL) is unclear. This post hoc analysis assessed the impact of recurrence on HRQoL using data from the phase 3 CheckMate 274 trial. Methods: Pts who had undergone radical surgery for high-risk MIUC (≤ 120 days previously) were randomized 1:1 to nivolumab 240 mg Q2W or placebo for ≤ 1 year. HRQoL was assessed using the EORTC QLQ-C30 and EQ-5D-3L every 4–6 weeks during treatment; 35 and 115 days after the last dose; and every 3 months after that until the end of the study (EQ-5D-3L only). The analysis included pts with a valid HRQoL assessment at baseline and at ≥1 post-baseline visits. Confirmed deterioration in HRQoL was defined as worsening exceeding an a priori points threshold (± 10 for the EORTC QLQ-C30 domains, –7 for the EQ-5D visual analogue scale [VAS]) at ≥ 2 consecutive visits. Recurrence was classified as local only or distant (with or without local recurrence). The effect of recurrence on HRQoL deterioration was assessed by Cox proportional hazards regression with recurrence as a time-dependent covariate. The models controlled for treatment arm and baseline HRQoL score, and were stratified by PD-L1 expression, pathologic nodal status, and use of neoadjuvant cisplatin-based chemotherapy. Results: The analysis included 645 pts for EORTC QLQ-C30, of whom 71 (11%) had local recurrence only and 136 (21%) had distant recurrence during the HRQoL assessment period; and 648 pts for EQ-5D-3L. with recurrence had a significantly higher risk of confirmed deterioration in all HRQoL domains than those without recurrence (see table). However, hazard ratios were consistently greater for distant recurrence than for local recurrence across all HRQoL domains. For local recurrence only, a higher risk of confirmed deterioration in HRQoL compared to no recurrence was observed only for global health status/QoL. Conclusions: Recurrence, particularly distant recurrence, had a significant, negative impact on HRQoL. This suggests that treatment delaying recurrence after radical surgery for high-risk MIUC may prevent or delay HRQoL deterioration in these pts. Clinical trial information: NCT02632409. [Table: see text]
Survival outcomes in patients receiving immune checkpoint inhibitor (ICI) for metastatic small cell urothelial cancer (SCUC).
Authors: Alhalabi Omar , Wilson Nathaniel , Navai Neema , Campbell Matthew T , Shah Amishi Yogesh , Gao Jianjun , Corn Paul G. , Aparicio Ana , Czerniak Bogdan , Guo Charles , Logothetis Christopher , Tannir Nizar M. , Choi Seungtaek , Siefker-Radtke Arlene O. 
Published: June 2021

4543 Background: The prognosis in patients with metastatic SCUC (mSCUC) remains poor with median survival around 1 year with systemic chemotherapy. We aimed to investigate the impact of ICI on survival of patients with mSCUC. Methods: Patients who received systemic therapy at MD Anderson Cancer Center (MDACC) for de novo or metachronous mSCUC after completing local management. within 12 months of neoadjuvant or adjuvant chemotherapy were included in this cohort, with overall survival (OS) calculated from the time of receipt of initial chemotherapy. Hazard ratios (HR) and 95% confidence intervals (95% CI) were calculated using logrank test. Results: 102 patients with mSCUC received systemic therapy at MDACC between April 2006 and June 2020. Median age was 66 (range 24 – 86 years), male to female ratio was 5. Bladder was the primary site in 85 (83%), 45 (44%) had prior cystectomy and 9 (9%) had prior nephroureterectomy. Histologies included 51 (50%) with predominant small cell (SC) features, 28 (27%) with focal SC features, 20 (20%) with pure SC, and 3 (3%) mixed with large cell component. Thirty-nine (38%) received ICI during their disease course: 29 (28%) following front-line chemotherapy (15 of whom within 12 months of neoadjuvant/adjuvant platinum therapy), 5 (5%) combined with front-line chemotherapy, and 5 (5%) received ICI front-line (two of whom were able to receive second-line chemotherapy). ICI agents used included anti-PD-1 (n=19), anti-PD-L1 (n=12), anti-PD-1/anti-CTLA-4 (n=5), anti-PD-1/anti-TIM3 (n=1), anti-PD-1/anti-STAT3 (n=1), anti-PD-L1/PARPi (n=1). Those who received ICI at any time had an improved median OS compared to those treated with chemotherapy alone (20.1 vs 12 months), [HR=0.45, 95% CI 0.27-0.72, p=0.003]. When we limited the analysis to those with de novo mSCUC (n=36), those who received ICI at any time (n=13) had an improved median OS compared to those treated with chemotherapy alone (n=23) (not reached vs 9.41 months), [HR=0.28, 95% CI 0.12-0.68, p=0.03]. Among patients who received ICI (n=39), median OS in those with liver metastases (n=11) was numerically shorter than those without (n=28) (13.1 vs 21.6 months), [HR=1.83, 0.59-5.7, p=0.21]. Conclusions: ICI improves OS for patients with mSCUC. Although clinical trials remain difficult in these rare variants, further prospective studies are indicated to confirm this finding.
Association of C-reactive protein (CRP) with efficacy of avelumab + axitinib (A + Ax) in advanced renal cell carcinoma (aRCC): Long-term follow-up results from JAVELIN Renal 101.
Authors: Tomita Yoshihiko , Larkin James , Venugopal Balaji , Haanen John B. A. G. , Kanayama Hiro-Omi , Eto Masatoshi , Grimm Marc-Oliver , Fujii Yosuke , Umeyama Yoshiko , Mariani Mariangela , Di Pietro Alessandra , Choueiri Toni K. 
Published: June 2021

4548 Background: CRP is an important prognostic and predictive factor in patients with aRCC receiving various therapies, such as cytokines and tyrosine kinase inhibitors. In this extended follow-up to the phase 3 JAVELIN Renal 101 trial (NCT02684006), we report the association of CRP levels at baseline (BL) and early after treatment with the efficacy of A + Ax or sunitinib (S). Methods: CRP levels were assessed at screening and day 1 of each 6-week cycle. Patients were categorized into CRP normal (BL CRP < 10 mg/L), normalized (BL CRP ≥10 mg/L and ≥1 CRP value decreased to < 10 mg/L during 6 weeks of treatment), and non-normalized (CRP ≥10 mg/L at BL and during 6 weeks of treatment) groups. Multivariate analysis of BL characteristics, including CRP for efficacy, was also conducted. Progression-free survival (PFS) and best overall response per independent central review (RECIST 1.1) from the second interim analysis (IA2) of overall survival (OS) and OS from the third interim analysis (IA3) were assessed. Results: Minimum duration of follow-up for IA2 and IA3 were 13 and 28 months, respectively. The table shows objective response rate (ORR), PFS, and OS by CRP group. Efficacy outcomes in the normal and normalized groups were favorable compared with the non-normalized group with both A + Ax and S. In the A + Ax arm, the complete response rate was 11.8% (normalized group), 3.8% (normal group), and 0.9% (non-normalized group). With A + Ax, the PFS in the normalized group was longer than in the normal group, but this was not observed with S. In each CRP group, all efficacy outcomes were favorable with A + Ax vs S. In the multivariate analysis, normalized or non-normalized CRP was an independent predictive factor of ORR or OS with A + Ax. Conclusions: Normal and normalized CRP levels were associated with improved A + Ax efficacy. A + Ax demonstrated favorable efficacy across CRP groups. OS in this study was immature; follow-up for the final analysis is ongoing. Further research in defining predictive value of CRP is warranted. Clinical trial information: NCT02684006. [Table: see text]
The impact of antibiotic (Ab) exposure on clinical outcomes in patients with metastatic renal cell carcinoma (mRCC) treated with immune checkpoint inhibitors (ICI) or VEGF targeted therapy (VEGF-TT).
Authors: Ernst Matthew Scott , Abou Alaiwi Sarah , Dizman Nazli , Labaki Chris , Nuzzo Pier Vitale , Adib Elio , Schmidt Andrew Lachlan , Meza Luis A , Gan Chun Loo , Wells J Connor , Bakouny Ziad , Pal Sumanta K. , Choueiri Toni K. , Heng Daniel Yick Chin , Dudani Shaan 
Published: June 2021

4552 Background: Retrospective studies have shown an association between Ab exposure and inferior clinical outcomes in patients receiving ICI across various tumor types, including mRCC. However, it is unclear whether Ab exposure has a unique interaction with ICI or is an independent prognostic marker, regardless of treatment. We sought to examine Ab exposure and its association with clinical outcomes in patients with mRCC treated with ICI compared to VEGF-TT. Methods: We identified patients treated with ICI (anti-PD-L1 alone or in combination with VEGF or CTLA4 inhibitor) or VEGF-TT alone in first to fourth line settings from 2009-2020 across 3 academic centers in North America. Ab exposure was defined as administration of Ab within 60 days prior to initiation of systemic therapy. Outcomes of interest were response rate (RR), time to treatment failure (TTF) and overall survival (OS). Multivariable Cox regression was performed to control for imbalances in International mRCC Database Consortium (IMDC) risk factors, histology, and treatment line. Results: We identified 748 patients. Among the ICI (n=427) and VEGF-TT (n=321) cohorts, 13% vs 15% (p=0.47) had Ab exposure and 57% vs 48% (p=0.046) were treated in the first line setting. The proportion of favorable, intermediate, and poor risk disease by IMDC criteria differed between Ab exposed and unexposed patients in the ICI (14% vs 18%, 47% vs 62%, 39% vs 21% p=0.03) and VEGF-TT (7% vs 13%, 43% vs 60%, 50% vs 27%, p=0.01) cohorts. RR, TTF and OS results are displayed in Table 1. Multivariable analysis did not show a significant independent association between Ab exposure and OS in both the ICI (HR 1.13, p=0.62) and VEGF-TT (HR 1.32, p=0.16) cohorts. Treatment modality (ICI vs VEGF-TT) did not modify the effect of Ab exposure on OS (p=0.84). Conclusions: Ab exposure was associated with higher IMDC risk scores in both the ICI and VEGF-TT cohorts as well as inferior OS on univariable analysis. After adjusting for IMDC risk factors, histology and treatment line, we were unable to find an independent association between Ab exposure and OS in multivariable analysis for either cohort.[Table: see text]
Outcomes of first-line (1L) ipilimumab and nivolumab (IPI-NIVO) and subsequent therapy in metastatic renal cell carcinoma (mRCC): Results from the International mRCC Database Consortium (IMDC).
Authors: Gan Chun Loo , Wells J Connor , Schmidt Andrew Lachlan , Powles Thomas , Tran Ben , Meza Luis A , Labaki Chris , Lee Jae-Lyun , Wood Lori , Shapiro Julia , Ernst D. Scott , Kapoor Anil , Canil Christina M. , Yuasa Takeshi , McKay Rana R. , Beuselinck Benoit , Donskov Frede , Dudani Shaan , Choueiri Toni K. , Heng Daniel Yick Chin 
Published: June 2021

4554 Background: IPI NIVO is approved for 1L treatment of IMDC intermediate/poor risk mRCC based on the CHECKMATE 214 trial. Herein, we report the clinical effectiveness of 1L IPI NIVO and second line (2L) therapy in the real-world setting. Methods: Using the IMDC dataset, patients (pts) treated with 1L IPI NIVO were identified. The outcomes of interest were 1L and 2L overall response rate (ORR), treatment duration (TD), time to next treatment (TTNT), and overall survival (OS). Results: 706 pts were included: 9% (57/614), 58% (354/614), and 33% (203/614) were IMDC favorable (fav), intermediate (int), and poor risk, respectively. Median age was 61 years. The majority of pts were males (71%), had clear cell histology (85%), and underwent nephrectomy (61%). 36%, 19%, and 8% of patients had bone, liver, and brain metastases, respectively. The 12-month OS for pts with IMDC fav, int, and poor risk disease was 92%, 79%, and 56%, respectively (p<0.01). The corresponding estimates for 24 months were 80%, 69%, and 38% (p<0.01). Pts who responded (39%) were more likely to have better IMDC risk category (p=0.02), received nephrectomy (p=0.04), normal neutrophil count (p<0.01), and clear cell histology (p=0.01). Pts with progressive disease as best response (27%) were more likely to have not received nephrectomy (p<0.01), worse IMDC risk category (p=0.02), bone metastases (p=0.01), liver metastases (p=0.04), and non-clear cell histology (p=0.01). Of the 66% (466/706) of pts who discontinued 1L IPI NIVO, 51% (236/466) received 2L therapy: sunitinib (40%), cabozantinib (25%), pazopanib (18%), axitinib (8%), and others (9%). The ORR, median TD, and median OS for those who received either sunitinib, cabozantinib, pazopanib or axitinib was 16%, 4.5 months (mo) (95% CI 3.7-5.6), and 14.5 mo (95% CI 10.9-25.9), respectively. 33% (129/386) of pts discontinued IPI NIVO due to irAEs. Conclusions: Our study benchmarks the real-world experience of 1L IPI NIVO in mRCC. IMDC criteria is prognostic for clinical outcome. Tyrosine kinase inhibitors have clinical activity post IPI NIVO.[Table: see text]