bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neoadjuvant FOLFIRINOX versus adjuvant gemcitabine in pancreatic cancer.
Authors: Wolfe Adam R , Miller Eric David , Abushahin Laith I. , Cloyd Jordan , Manilchuck Adrei , Dillhoff Mary , Diaz Pardo Dayssy Alexandra , Noonan Anne M. , Williams Terence M 
Published: May 2019

4123 Background: In the metastatic or adjuvant setting for pancreatic cancer, the combination chemotherapy of fluorouracil, leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX) resulted in longer overall survival (OS) compared to gemcitabine therapy. We conducted an institutional study to compare the efficacy of neoadjuvant modified FOLFIRINOX (neo-mFOLFIRINOX) to adjuvant gemcitabine (adj-gem) for pancreatic cancer patients who completed resection. Methods: The study retrospectively enrolled patients from 2006 to 2017 from Ohio State University. While patients who received adjuvant gemcitabine were considered to be resectable upfront, patients who received neo-mFOLFIRINOX were either staged as borderline resectable (BR) or un-resectable (UR) by the institutional tumor board group. 111 patients received adj-gem (average cycles, 5.5) and 52 patients received neo-mFOLFIRINOX (average cycles, 3.5). The survival rates were determined by the Kaplan-Meier method and analyzed using Cox regression and log-rank test. Results: At a median follow up of 21.3 months, the median OS was 35.4 months in the neo-mFOLFIRINOX group and 21.8 months in the adj-gem group (hazard ratio, 0.56, 95% confidence interval (CI), 0.37-0.84 p = 0.005). The OS rate at 3 years was 46% in the neo-mFOLFIRINOX group and 22% in the adjuvant gemcitabine group (p = 0.001). The median disease free survival (DFS) was 18.6 months in the neo-mFOLFIRINOX group and 12.0 months in the adj-gem group (hazard ratio, 0.63, 95% CI, 0.43-0.93 p = 0.022). The DFS rate at 3 years was 17% in the neo-mFOLFIRINOX group and 11% in the adj-gem group (p = 0.02). On surgical pathological specimen review, the neo-mFOLFIRINOX group had statistically (p < 0.05) lower tumor grade, lower rates of perineural invasion and lymphovascular invasion, lower pathological T stage, lower pathological N stage, and lower number of nodes positive compared to the adj-gem group. Frequencies of obtaining R0 resections were higher in the neo-mFOLFIRINOX versus adj-gem groups but not statistically different (51.9% vs 40.4, p = 0.2). The average age and performance status were similar between the two groups. Conclusions: At our institution, BR and UR pancreatic cancer patients who received neo-mFOLFIRINOX and completed resection had longer OS, DFS, and more favorable pathological indicators compared to those patients who had upfront surgery and adjuvant gemcitabine. Randomized clinical trials comparing neoadjuvant versus adjuvant FOLFIRINOX are needed to validate these findings.
Elevated pretreatment serum IL-8 and PD-L1 and overall survival in a phase III randomized advanced pancreatic cancer clinical trial.
Authors: Maddukuri Ashok , Moku Prashanth Reddy , Polimera Hyma Vani , Nagabhairu Vinod , Ali Suhail M. , Leitzel Kim , Drabick Joseph J. , Halstead Scott , Umstead Todd , Mckeone Daniel , Ali Aamnah , Poulose Joyson , Pancholy Neha , Menon Harry , Spiegel Howard , Lipton Allan 
Published: May 2019

4131 Background: We previously reported the prognostic and predictive utility of pretreatment serum PD-L1 in the CCTG MA.31 serum bank (SABCS 2018, abstr PD3-10). IL-8 (CXCL8) is a pro-inflammatory cytokine that binds to CXCR1 and CXCR2 and promotes tumor immune escape and progression. High serum IL-8 levels are associated with poor prognosis in many cancers, and have recently been reported to predict for reduced OS to nivolumab in lung cancer and melanoma (ASCO 2018, abstr #3025). In this study, we retrospectively evaluated combined pretreatment serum IL-8 and PD-L1 on overall survival (OS) from a phase III randomized pancreatic cancer trial of first-line therapy (octreotide + 5-FU vs. 5-FU) that had reported no significant OS difference between treatment arms. Methods: This study had 147 patients with serum available for this retrospective biomarker analysis from an advanced pancreatic cancer phase III clinical trial.TheELLA immunoassay platform (ProteinSimple, San Jose, CA) was utilized to quantitate serum levels of IL-8 and PD-L1. Kaplan-Meier life table analysis was used to correlate serum biomarkers with overall survival (OS). Results: In univariate analysis, pretreatment serum IL-8 was a significant biomarker as a continuous variable (HR = 1.004; p = 0.012) and trended significant at the median cutpoint (HR = 1.379; p = 0.098) for OS, however serum PD-L1 was not significant at any cutpoint. When serum PD-L1 and IL-8 levels were analyzed as combined biomarkers (median cutpoints), the serum IL-8 high / PD-L1 high cohort had a significantly shorter OS vs the serum IL-8 low / PD-L1 low cohort (HR = 1.816; p = 0.017). Conclusions: In this phase III randomized clinical trial in advanced pancreatic cancer, pretreatment serum IL-8 was a significant biomarker for OS, but serum PD-L1 was not. Higher combined pretreatment serum levels of PD-L1 and IL-8 (both biomarkers high vs. both low) were prognostic for reduced OS in this phase III pancreatic cancer trial. Further study of circulating IL-8 and PD-L1 is warranted in pancreatic cancer for evaluation of targeted and investigational therapies, including the immune checkpoint inhibitors and anti-IL8 therapy.
Improved overall survival (OS) for advanced pancreatic cancer (PDAC) patients (pts) enrolled in the Know Your Tumor (KYT) program whose tumors harbored highly actionable molecular alterations and who received molecularly-matched therapies (tx).
Authors: Pishvaian Michael J. , Blais Edik Matthew , DeArbeloa Patricia , Brody Jonathan Robert , Rahib Lola , Hendifar Andrew Eugene , Mikhail Sameh , Chung Vincent , Sohal Davendra , Picozzi Vincent J. , Mason Kimberly , Tibbetts Lisa , Lyons Emily , Matrisian Lynn McCormick , Madhavan Subha , Petricoin Emanuel 
Published: May 2019

4138 Background: Initial results from the KYT program demonstrated that 27% of PDACs harbor highly actionable molecular alterations (herein labelled “actionable biomarkers”), defined as biomarkers that predict for a high response rate to appropriately targeted tx, in any cancer type. Within this cohort, the median progression-free survival on molecularly-matched tx was 2 months longer than unmatched tx. Here, we present OS data emphasizing the 125 pts with “actionable biomarkers” who did or did not receive molecularly-matched tx. Methods: PanCAN and Perthera have coordinated tumor molecular profiling through commercial labs (NGS/IHC panels) for PDAC pts since 2014. Results are reviewed by a molecular tumor board, and tx options are prioritized based on the actionable biomarkers, in the context of the pt’s tx history. Pts are followed longitudinally to track physician tx choices and survival outcomes. Cox regression was used to assess differences in OS (measured from date of diagnosis until death). Results: Of 1053 pts who received a Perthera Report, 25% had “actionable biomarkers”. OS analyses across 454 pts with adequate tx history are shown in the Table below. Notably, pts with “actionable biomarkers” who received a molecularly-matched tx had a significantly increased OS compared to those with “actionable biomarkers” but who did not receive molecularly-matched tx. Subgroup analyses related to tx history and specific molecular pathways that warrant further investigation will be discussed. Conclusions: When the ~25% of PDAC pts whose tumors harbored “actionable biomarkers” received molecularly-matched tx, they had a better OS. These findings support the need to test all pts with PDAC, and just as importantly, to maximize access to molecularly-matched tx for appropriate pts, to achieve the best pt outcomes. [Table: see text]
Pembrolizumab (pembro) plus axitinib (axi) versus sunitinib as first-line therapy for metastatic renal cell carcinoma (mRCC): Outcomes in the combined IMDC intermediate/poor risk and sarcomatoid subgroups of the phase 3 KEYNOTE-426 study.
Authors: Rini Brian I. , Plimack Elizabeth R. , Stus Viktor , Gafanov Rustem , Hawkins Robert , Nosov Dmitry , Pouliot Frederic , Soulieres Denis , Melichar Bohuslav , Vynnychenko Ihor , Azevedo Sergio Jobim , Borchiellini Delphine , McDermott Raymond S. , Bedke Jens , Tamada Satoshi , Wan Shuyan , Perini Rodolfo F. , Chen Mei , Atkins Michael B. , Powles Thomas 
Published: May 2019

4500 Background: In KEYNOTE-426, pembro + axi significantly improved OS (HR 0.53, P < .0001), PFS (HR 0.69, P = .0001), and ORR (59.3% vs 35.7%, P < .0001) vs sunitinib and had manageable toxicity as first-line therapy for mRCC (NCT02853331). The pembro + axi benefit was observed across all IMDC risk groups and regardless of PD-L1 expression. We present data for the combined intermediate/poor risk group and for patients (pts) with sarcomatoid features. Methods: 861 eligible pts with clear-cell mRCC, no prior systemic therapy for mRCC, and KPS ≥70 were randomized 1:1 to pembro 200 mg IV Q3W for a maximum of 35 cycles plus axi 5 mg orally BID (N = 432) or sunitinib 50 mg orally QD (4-wk on/2-wk off) (N = 429). Primary endpoints were OS and PFS (RECIST v1.1 by blinded, independent central review [BICR]). ORR (RECIST v1.1 by BICR) was the key secondary endpoint. The intermediate/poor risk group was prespecified; the sarcomatoid group was exploratory. HRs and their 95% CIs were calculated with a Cox proportional hazards model. None of the analyses were multiplicity-controlled. Results: 592 (68.8%) of all randomized pts were of IMDC intermediate/poor risk — 294 in the pembro + axi arm, 298 in the sunitinib arm. Pembro + axi improved OS (HR 0.52, 95% CI 0.37-0.74; 12-mo rate 87.3% vs 71.3%), PFS (HR 0.67, 95% CI 0.53-0.85; median 12.6 vs 8.2 mo), and ORR (55.8% [95% CI 49.9-61.5] vs 29.5% [24.4-35.1]) in pts with intermediate/poor risk; CR rates were 4.8% (95% CI 2.6-7.9) vs 0.7% (0.1-2.4). Of the 578 pts with known status, 105 (18.2%) had sarcomatoid features — 51 in the pembro + axi arm, 54 in the sunitinib arm. Pembro + axi improved OS (HR 0.58, 95% CI 0.21-1.59; 12-mo rate 83.4% vs 79.5%), PFS (HR 0.54, 95% CI 0.29-1.00; median not reached vs 8.4 mo), and ORR (58.8% [95% CI 44.2-72.4] vs 31.5% [19.5-45.6]) in pts with sarcomatoid features; CR rates were 11.8% (95% CI 4.4-23.9) vs 0% (0.0-6.6). Conclusions: Pembro + axi provides benefit in the combined population of pts with IMDC intermediate or poor risk and in pts whose tumors had sarcomatoid features. The observed benefits were consistent with those seen in the total population. Clinical trial information: NCT02853331.
Clinical outcomes according to PD-L1 status and age in the prospective international SAUL study of atezolizumab (atezo) for locally advanced or metastatic urothelial carcinoma (UC) or non-UC of the urinary tract.
Authors: Sternberg Cora N. , Merseburger Axel Stuart , Choy Ernest , Castellano Daniel E. , Lopez-Rios Fernando , James Nicholas , Banna Giuseppe Luigi , De Giorgi Ugo , Masini Cristina , Bamias Aristotelis , Garcia del Muro Xavier , Powles Thomas , Duran Ignacio , Gedye Craig , Gamulin Marija , Zengerling Friedemann , Geczi Lajos , de Ducla Sabine , Fear Simon , Loriot Yohann 
Published: May 2019

4519 Background: Atezo, a monoclonal antibody targeting PD-L1, is an approved therapy for locally advanced/metastatic UC based on IMvigor210 and IMvigor211 phase II and III trials. The single-arm SAUL study (NCT02928406) with a broader patient (pt) population demonstrated median overall survival (OS) of 8.7 months and a safety profile consistent with previous atezo trials. Methods: Pts with locally advanced/metastatic UC or non-UC of the urinary tract received atezo 1200 mg every 3 weeks until disease progression or unacceptable toxicity. Populations excluded from IMvigor211 (renal impairment, ECOG PS 2, treated asymptomatic CNS metastases, stable controlled autoimmune disease, concomitant steroids, HIV positive, non-UC) were eligible. The primary endpoint was safety; OS and overall response rate (ORR) were secondary endpoints. Predefined subgroup analyses included outcomes according to PD-L1 status (VENTANA SP142) and age in the overall population (and the IMvigor211-like subgroup for PD-L1). Results: Between Nov 2016 and Mar 2018, 1004 pts were enrolled; 997 received atezo. Efficacy is summarized below. Incidences of grade ≥3 treatment-related adverse events were similar irrespective of PD-L1 status (overall IC 0/1 vs 2/3: 11% vs 16%; IMvigor211-like IC 0/1 vs 2/3: 11% vs 15%) or age (≥65 y: 13%; ≥75 y: 12%; ≥80 y: 10%). Conclusions: OS and ORR appear more favorable in IC 2/3 vs IC 0/1 subgroups (overall and in the IMvigor211-like population). Atezo was effective and well tolerated across subgroups including elderly pts. Clinical trial information: NCT02928406. [Table: see text]
Circulating cell-free DNA (cfDNA) levels and fragmentation pattern can distinguish nonmuscle invasive (NMI) from muscle-invasive (MI) and metastatic (met) bladder cancer (BC).
Authors: Fallah Jaleh , Ganguly Shinjini , Li Hong , Wei Wei (Auston) , Balyimez Aysegul , Sitalaximi Thirunavukkarasu , Diaz-Montero C. Marcela , Rayman Patricia A. , Lamenza Marcelo , Dann Priscilla , Company Donna , Tendulkar Rahul D. , Abazeed Mohamed , Garcia Jorge A. , Ornstein Moshe Chaim , Rini Brian I. , Lee Byron H , Grivas Petros , Mian Omar Y. 
Published: May 2019

4523 Background: Occult MI and met BC may be under-staged. Circulating cfDNA may be a dynamic, low-cost and minimally invasive biomarker. We evaluated correlations between total circulating cfDNA and presence of MIBC and met BC. We hypothesized that the relative abundance of circulating low molecular weight cfDNA would correlate with BC stage. Methods: Peripheral blood from pts with BC was collected in Streck BCT tubes and processed to obtain cf nucleic acid extracts. Total cfDNA quantity (ng/ml) was assessed by fluorimetry. cfDNA fragment size was measured by Bioanalyzer DNA analysis. Wilcoxon rank sum test and Fisher’s Exact test were used to compare cfDNA quantity and fragmentation pattern among pts with NMIBC, MIBC, met BC. Results: Blood was obtained from 58 pts with BC (20% women, 34% never smokers, median age 71 (29-89). There was no significant difference in cfDNA between MIBC and met BC, however, it was significantly lower in pts with NMIBC vs MIBC and met BC (table). The concentration of low molecular weight fragments (LMW-frags) (100 - 400) base pairs and the ratio of LMW-Frag to cfDNA were significantly different between pts with NMIBC and pts with MIBC or met BC (table). Using median values as the cutoff, there was a significantly higher proportion of pts with cfDNA > 7 ng/ml and LMW-frags > 1.6 ng/mL, in MIBC & met BC vs NMIBC (p < 0.001). The % of pts with LMW-frags to cfDNA > 30%, was significantly different among NMIBC, MIBC and met BC groups: 16%, 53%, 78%, respectively (p < 0.001). Conclusions: This exploratory study suggests that cfDNA levels may correlate with BC stage. Measuring the relative abundance of LMW-frags with the expected size of cf DNA can enhance the specificity of cfDNA analysis for distinction between MIBC and met BC. Further studies are needed to confirm findings and define the optimal cut-points for optimal BC staging. [Table: see text]
Nivolumab monotherapy in patients with advanced platinum-resistant urothelial carcinoma: Efficacy and safety update from CheckMate 275.
Authors: Siefker-Radtke Arlene O. , Baron Ari David , Necchi Andrea , Plimack Elizabeth R. , Pal Sumanta K. , Bedke Jens , Zakharia Yousef , Grimm Marc-Oliver , Bracarda Sergio , Retz Margitta , Ohyama Chikara , Grossfeld Gary , Collette Sandra , Sharma Padmanee , Galsky Matt D. 
Published: May 2019

4524 Background: In the open-label, single-arm, phase 2 CheckMate 275 trial, objective response rate (ORR) for patients (pts) with metastatic urothelial carcinoma (mUC) with nivolumab (NIVO) was 20.4% with minimum follow-up of 21.3 mo. Here, we report updated efficacy and safety data with minimum follow-up of 33.7 mo. Methods: Pts with platinum-resistant locally advanced or metastatic urothelial carcinoma received NIVO 3 mg/kg until disease progression or unacceptable toxicity. The primary endpoint was ORR by blinded independent review committee (BIRC) by RECIST v1.1 (including duration of response [DOR]). Secondary endpoints included progression-free survival (PFS) by BIRC, overall survival (OS), and ORR per investigator. Efficacy was evaluated in all treated pts and by tumor PD-L1 expression. Safety and PFS by investigator were exploratory endpoints. Results: ORR by BIRC was 20.7% (95% CI 16.1–26.1) including 18 (7%) complete responses (CR; with 1 additional CR since the last report; Table). ORR per investigator was similar (24.8%). Median DOR by BIRC was 20.3 mo (95% CI 11.5–31.3). Of 56 pts with best overall response (BOR) of CR or partial response (PR), 59% had a DOR ≥12 mo. Median PFS (mPFS) was 1.9 mo per BIRC (95% CI 1.9–2.3; Table) and 2.0 mo per investigator (95% CI 1.9–2.5). Median OS (mOS) was 8.6 mo (95% CI 6.1–11.3; Table). 12, 24, and 36-mo OS rates were 40%, 30%, and 22%. While efficacy was numerically higher in pts with tumor PD-L1 expression ≥1%, efficacy was observed in all pts (Table). Any-grade treatment-related adverse events occurred in 69% of pts (grade 3–4, 25%), mostly (59%) within the first 3 mo of initiating therapy. Conclusions: With long-term follow-up from CheckMate 275, NIVO continues to provide durable antitumor activity in pts with mUC. No new safety signals were noted. Clinical trial information: NCT02387996. [Table: see text]
Durability of complete response (CR) with atezolizumab (atezo) in locally advanced/metastatic urothelial carcinoma (mUC).
Authors: Loriot Yohann , Balar Arjun Vasant , Dreicer Robert , Hoffman-Censits Jean H. , Perez-Gracia Jose Luis , Petrylak Daniel Peter , Van Der Heijden Michiel Simon , Shen Xiaodong , Zhu Qian (Cindy) , Ding Beiying , Kaiser Constanze , Rosenberg Jonathan E. 
Published: May 2019

4527 Background: Atezo (anti–PD-L1) has been shown to elicit CRs in a number of mUC patients (pts) in clinical trials. We sought to describe the kinetics, durability and outcomes associated with these CRs in Ph I (PCD) and II (IMvigor210) atezo studies, each with long-term follow-up. Methods: In PCD (pre-treated mUC) and IMvigor210 (Cohort 1, cisplatin-ineligible untreated mUC; Cohort 2, platinum-treated mUC), pts received atezo per protocol (Petrylak JAMA Oncol 2018; Balar Lancet 2017; Rosenberg Lancet 2016). This post hoc analysis descriptively assessed pt disposition, time to and duration of RECIST 1.1 response and overall survival in pts with CR. Results: CR rates were 13%, 8% and 7% in PCD, IMvigor210 Cohort 1 and Cohort 2, respectively. First response was PR in most pts with CR. Median CR duration was > 3 y in PCD, not estimable (NE) in IMvigor210 Cohort 1 and > 2 y in Cohort 2 (Table). At data cutoff, all but 2, 0 and 1 pts were alive, respectively; across studies, ≥ 40% of pts with CR were on treatment. CR pts had a first response (PR/CR) by a median of 3.5 cycles. Further pt characteristics and survival outcomes will be reported. Conclusions: Across Ph I/II atezo mUC studies, CRs appeared durable (median duration > 2 y) despite small pt numbers. Most pts with CR were alive, with responses ongoing after long-term follow-up (median follow-up > 30 mo). Clinical trial information: NCT01375842, NCT02951767, NCT02108652. [Table: see text]
Association of cell-free DNA (cfDNA) levels with myeloid-derived suppressor cells (MDSC) levels in blood of patients (pts) with muscle invasive (MI) and metastatic (met) bladder cancer (BC).
Authors: Fallah Jaleh , Ganguly Shinjini , Rayman Patricia A. , Wei Wei (Auston) , Balyimez Aysegul , Sitalaximi Thirunavukkarasu , Lamenza Marcelo , Stephans Kevin L. , Dann Priscilla , Company Donna , Tendulkar Rahul D. , Abazeed Mohamed , Garcia Jorge A. , Rini Brian I. , Lee Byron H , Ornstein Moshe Chaim , Grivas Petros , Mian Omar Y. , Diaz-Montero C. Marcela 
Published: May 2019

4528 Background: cfDNA can be detected in healthy individuals but higher concentrations are present in pts with cancer. MDSC are immature immunosuppressive cells that can be mobilized from bone marrow by tumor-related factors. Higher blood MDSC levels have been associated with worse outcomes in pts with solid tumors including BC. We assessed correlations between cfDNA and MDSC levels in pts with MIBC and met BC. Methods: Peripheral blood from pts with MIBC and met BC was collected in Streck BCT tubes and processed to obtain cf nucleic acid extracts. Total cfDNA was determined by fluorimetry. Cell-free DNA fragment size was measured by Bioanalyzer DNA analysis; 100-400 bp fragments (mono- and di-nucleosomal fragments linked to granulocytic processing of apoptotic and necrotic tumor cells) were designated low molecular weight (LMW-frags). The % of MDSC (CD33+/HLADR-) and subtypes were measured. MDSC subtypes were defined as polymorphonuclear (PMN-MDSC: CD15+/CD14-), monocytic (M-MDSC: CD15-/CD14+) and uncommitted (UNC-MDSC: CD15-/CD14-). Spearman’s correlation test was used for analysis. Results: Blood from 37 pts (19% women, 40% never smokers) with MIBC or met BC was collected: 15 (41%) with MIBC and 22 (59%) with met BC at time of collection. There was a significantly positive correlation between total MDSC and cfDNA levels (r = 0.57, P = 0.0003). Among MDSC subtypes, there was a significantly positive correlation between PMN-MDSC and cfDNA levels (r = 0.61, P < 0.0001). The higher level of LMW-frags was significantly but moderately associated with higher total MDSC (r = 0.43, P 0.008) and PMN-MDSC (r = 0.41, P 0.01) levels. There was no significant correlation between cfDNA level and other MDSC subtypes. Conclusions: There was a positive correlation between total and PMN-MDSC with cfDNA levels in blood from pts with MIBC and met BC. That may suggest a putative role for MDSC in mediating cfDNA release into the circulation, consistent with prior reports of granulocyte-mediated ctDNA processing. Further studies need to identify mechanisms and implications of our findings and potential correlation with clinical outcomes.