bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy and safety of surufatinib in United States (US) patients (pts) with neuroendocrine tumors (NETs).
Authors: Dasari Arvind , Li Daneng , Sung Max W. , Tucci Christopher , Kauh John S. , Kania Marek K. , Paulson Andrew Scott 
Published: May 2020

4610 Background: Surufatinib (S) is a targeted inhibitor of tyrosine kinases VEGFR1, 2, & 3, FGFR1, and CSF-1R. Safety and efficacy of S has previously been studied in China in early phase development, and in 2 randomized phase 3 placebo controlled trials (NCT02588170 & NCT02589821). These trials enrolled pts with NETs of extrapancreatic (epNET) and pancreatic (panNET) origin, respectively. Both trials are completed, stopping at their pre-planned interim analysis after meeting the primary endpoint of improved PFS. S demonstrated significant efficacy in pts with advanced epNETs, achieving a median Progression Free Survival [mPFS] of 9.2 v 3.8 months when compared to placebo. The mPFS achieved in pts with advanced panNETs is currently pending future disclosure at an upcoming scientific conference. Methods: A dose escalation (ESC)/expansion (EXP) study was conducted to evaluate and confirm the effects of S in US pts. Dose ESC was completed and the maximum tolerated dose and recommend phase 2 dose was determined to be 300mg QD; the same as previous trials. The primary objective of EXP was to evaluate anticancer activity in pts with select indications including panNETs and epNETs. Results: As of 21-Jan-20, 32 pts with heavily pre-treated progressive NETs (median prior lines of treatment [Tx]: 3; range 1-8) were enrolled. The 32 pts included 16 pts with panNET and 16 with epNET. All previously received everolimus and/or sunitinib. The median duration of Tx at the time of the data cut-off was 19 wks for all pts; 30.9 wks for panNET and 11 for epNET. 19 pts remain on active Tx (13 epNET and 6 panNET pts), 9 pts discontinued due to progression of disease, 2 withdrew consent and 2 discontinued due to adverse event (AE) (grade 3 tricuspid valve insufficiency, and grade 3 GI bleed). An objective response rate of 9.4% was observed. 3 panNET pts achieved a confirmed partial response (PR) and 1 had an unconfirmed PR per RECIST 1.1; no epNET pts achieved a PR. The safety profile of S remains consistent with previously completed trials. 27 pts (84.4%) had reported at least one adverse event (AE), and 16 pts (50%) reported ≥ grade 3 AE’s. The most common AE’s reported were: hypertension, fatigue, diarrhea, proteinuria and nausea. Pharmacokinetics (PK) analyses has shown similar exposure in panNET and epNET pts as was observed in ESC, and pts from the collective pool of pts. Conclusions: S has demonstrated promising antitumor activity in US pts with progressive NETs with a manageable safety profile. Additionally, PK and dose exposure data is consistent with trial results from large randomized phase 3 trials. Clinical trial information: NCT02549937 .
Phase II clinical trial of nab-paclitaxel plus gemcitabine in elderly patients with previously untreated locally advanced or metastatic pancreatic adenocarcinoma: BIBABRAX study.
Authors: Feliu Batlle Jaime , Jorge Fernandez Monica , Macarulla Teresa , Massuti Bartomeu , Albero Ana , Gonzalez Federico , Quintero Aldana Guillermo Alfonso , Mingorance J. Ignacio Delgado , Fernandez Montes Ana , Garcia Piernavieja Carmen , Valladares-Ayerbes Manuel , García Girón Carlos , Mondejar Rebeca , Vicente Pilar , Casado Esther , Gonzalez Cebrian Irene , Lopez-Vivanco Guillermo 
Published: May 2020

4615 Background: FOLFIRINOX and nab-paclitaxel plus gemcitabine (nab-P+G) are the standard of care in the first-line treatment of mPC patients (pt) with good performance status. However, no standards of care exist for elderly ( > 70 years) pt as they are usually excluded in clinical trials. This study aimed to evaluate whether the clinical benefit of nab-P+G could be extended to elderly pt with mPC. Methods: This was an open-label, single-arm, multicenter, phase II trial, to assess the efficacy and safety of Nab-P+G in elderly pt (≥ 70 years) with ECOG PS 0–1 and untreated unresectable locally advanced or metastatic PC. Pt received four-week cycles of intravenous (i.v.) nab-paclitaxel 125 mg/m2, followed by i.v. gemcitabine 1,000 mg/m2, on days 1, 8 and 15, until disease progression. Efficacy was evaluated according RECIST v 1.1 criteria and safety according NCI-CTCAE v 4.0 criteria. Results: Eighty pt were enrolled in the study. Median age was 74.6 years (range 70-87.9), 57.5% were men, 71% had ECOG PS 1 and 86% metastatic disease. 16.3% of patients had a history of prior tumor surgical resection, 12.5% received chemotherapy and 3.8% radiotherapy. Primary tumor was located in head (32.5%), tail (25.0%) and body (22.5%). Nab-P and G was reduced in 49% and 41% of pt respectively. 15 pt definitely interrupt study treatment due to toxicity: neurotoxicity (7), asthenia (5), neutropenia (1), leukocytosis (1) and hepatotoxicity (1). Time until definite deterioration (reduction ≥10 points as compared to baseline in EORTC-QLQ C30) was 1.6 months and deterioration-free rate at 3 months was 54.3%. Overall response rate was 13.8%, clinical benefit rate 67.5%, median PFS 7.2 months and median OS 9.2 months. The most common treatment-related adverse events were asthenia (60.0%), diarrhea (40.0%), neutropenia (33.8%), hair loss (28.8%), thrombocytopenia (26.3%), and nausea (23.8%). Only asthenia and neutropenia presented a relatively high incidence of grade 3 and 4 toxicities (21.3%). At least 1 SAE was reported in 55% of pt. Conclusions: BIBABRAX study confirms the clinical benefit of nab-P+G in an elderly population with mPC, in terms of survival, clinical response and tolerance, therefore it could be considered a treatment option for elderly patients. However, it was unable to demonstrate the preplanned benefit on the quality of life. Further research is needed on treatment strategies that could reduce deterioration of the quality of life in these pt. Clinical trial information: NCT02391662 .
PANasta Trial: Cattell Warren versus Blumgart techniques of pancreatico-jejunostomy following pancreato-duodenectomy—A double-blinded multi-centered trial, trial results.
Authors: Halloran Christopher , Neoptolemos John P. , Platt Kellie , Jackson Richard , Reddy Srikanth , Oreilly Derek , Prachalias Andreas , Palmer Daniel H. , Menon Krishna , Davidson Brian , Gomez Dhanny , Ghaneh Paula 
Published: May 2020

4619 Background: Pancreatic anastomosis failure following pancreatic head excision, for suspected pancreatic cancer, leads to longer recovery and failure to start or complete adjuvant chemotherapy. The aim of this study is to evaluate whether a Blumgart anastomosis (BA) reduces the post operative pancreatic fistula (POPF) rate compared to a more traditional Cattell-Warren anastomosis (CWA). Methods: Patients with suspected pancreatic cancer, undergoing elective pancreato-duodenectomy were randomized intra-operatively to either a BA or a CWA. Anastomoses were constructed according to prior agreed techniques and an operative manual describing key surgical steps. Quality control of these key steps and adherence to the arm of randomization was ensured by operative photographs. Surgical drain amylase was measured post-operatively to establish the primary end point of POPF. These were graded A (biochemical) or B and C (clinically relevant, CR-POPF). Secondary endpoints included: Entry in adjuvant therapy, hospital stay, mortality and survival. Overall survival was estimated using the method of Kaplan Meier and defined as the time from randomisation until death by any cause with alive patients censored at the end of study date. Results: Between May 5 2015 and August 7 2017, 238 patients were randomized, 2 patients withdrew, leaving 236 patients for analysis (112 BA, 124 CWA). Median age was 70 years, 63% were men. Median time from diagnosis to randomization (surgery) was 33 days for both arms. In the BA arm there were 28 POPF’s (15-A, 10-B and 3-C) and 32 in the CWA arm (18-A, 12-B and 2-C), p = 0.887. In total 27 patients (11.4%) developed a CR-POPF, BA 13 (5.5%), CWA 14 (5.9%), p = 0.857. 75% of eligible patients entered chemotherapy, with a median (IQR) time to the start treatment of 2.55 (2.27, 3.15) months for the BA group and 2.87 (2.56, 3.75) for the CWA group. Median hospital stay (IQR) in days was 13 (10-24) for BA and 14.5 (10-22) for CWA, p = 0.232. The overall surgical related mortally at 90 days was 1.7%. 44 study deaths were observed, 35 were due to disease progression (BA 19, CWA 16). A hazard ratio (95% CI) of 0.72 (0.4, 1.311) shows better, but not statistically significant survival for the CWA group. Conclusions: This is the largest surgical trial ever conducted comparing these techniques and there was no significant difference in the POPF rate between the BA and CWA anastomoses. In a UK population the clinically relevant POPF rate is 11% and 75% of eligible patients enter chemotherapy. Clinical trial information: ISRCTN52263879 .
A phase II trial of preoperative FOLFIRINOX followed by gemcitabine-based chemoradiotherapy in patients with borderline resectable pancreatic ductal adenocarcinoma (BR PDAC).
Authors: Wysota Michael , Jirgal Amanda , Acuna-Villaorduna Ana , Viswanathan Shankar , Kaubisch Andreas , Gadde Eswar , Kabarriti Rafi , Goel Sanjay , Chuy Jennifer W. 
Published: May 2020

4638 Background: Preoperative (preop) therapy is widely accepted as the standard of care for patients (pt) with BR PDAC with limited evidence for a specific regimen. This study aimed to assess the efficacy of FOLFIRINOX (FOL) chemotherapy followed by gemcitabine-based chemo-radiotherapy (RT) as preop therapy in pt with BR-PDAC. Methods: This single arm Simon two stage phase II trial in pt with BR PDAC was conducted in two phases. The first phase included 4 cycles of FOL, and the second included weekly gemcitabine (1000 mg/m2) for 6 cycles with concomitant intensity-modulated RT (50.4 Gy in 28 fractions)(Gem/RT).The primary aim was to compare R0 resection rate (H0: ≤40% vs Ha≥60%) using one-sample one-sided Z test. Secondary outcomes, including overall survival (OS) and progression-free survival (PFS) were assessed using Kaplan-Meier method. Results: Of 22 enrolled pt, 18 (81.8%) completed preoperative treatment. Median age at diagnosis was 63.4 years and 12 (54.5%) were female. There were 10 (45.5%) Hispanics, 4 (18.2%) non-Hispanic black, and 8 (36.4%) non-Hispanic white. Tumor location was predominantly head/neck (21, 95.5%), 15 (68.1%) had T2/3, and 9 (40.9%) had N2 (clinical) disease. Fourteen (64.6%) pt, had venous involvement, 5 (22.7%) had arterial, and 3 (13.6%), both. In the first phase, 20 (90.9%) completed 4 cycles of FOL, 6 (27.3%) required dose-reduction and dose was delayed in 12 (54.5%). Stable disease (SD) was achieved in 10 (52.6%), partial response (PR) in 8 (42.1%) and disease progression (PD) in 1 (5.3%) pt. Of 21 pt that entered the second phase, 18 (85.7%) completed 6 cycles of Gem/RT, 5 (26.3%) required dose-reduction and dose was delayed in 6 (31.6%). SD was achieved in 10 (55.6%), PR in 3 (16.7%) and PD in 5 (27.8%). All pt experienced at least one grade 1 adverse event (AE) and 12 (54.5%) at least one grade 3/4 AE, of which neutropenia was the most common-11 (50%). Of the 15 (68.1%) pt who underwent surgical resection, 12 (80%) achieved R0 margins and 5 (33.3%) required vascular reconstruction. The R0 rate among pt that received >1 cycle of FOLFIRINOX was 54.5%. Adjuvant chemotherapy was offered to 6/15 pt (40%). The PFS and OS will be reported. Conclusions: An R0 resection rate of 54.5% with this limited sample size is significant at the 10% level. Neoadjuvant FOLFIRINOX followed by concomitant Gem/RT was well-tolerated. The study will be amended to include adjuvant FOL in line with the PRODIGE intergroup adjuvant study results. Clinical trial information: NCT01897454 .
Comprehensive analysis of KRAS variants in patients (pts) with pancreatic cancer (PDAC): Clinical/molecular correlations and real-world outcomes across standard therapies.
Authors: Hendifar Andrew Eugene , Blais Edik Matthew , Ng Camille , Thach Dzung , Gong Jun , Sohal Davendra , Chung Vincent , Sahai Vaibhav , Fountzilas Christos , Mikhail Sameh , Gregory Gary , Brody Jonathan Robert , Lyons Emily , DeArbeloa Patricia , Matrisian Lynn McCormick , Petricoin Emanuel , Pishvaian Michael J. 
Published: May 2020

4641 Background: Approximately 90% of PDAC tumors are driven by activating KRAS mutations. The biological and clinical impact of common KRAS variants (e.g. G12D, G12V, G12R) and less common variants (e.g. G12C, Q61H, Q61R) remains largely unknown despite the emergence of variant-specific treatment strategies. Methods: We retrospectively analyzed real-world outcomes from 1475 PDAC pts who underwent molecular profiling via the Know Your Tumor program. Overall survival (OS) and progression-free survival (PFS) were analyzed by choice of 1st line standard therapies. Outcomes in pts with specific KRAS mutations were compared against the KRAS G12D cohort using Cox regression. Based on our prior data, tumor profiles with actionable molecular findings (DDR mutations or other drivers) were evaluated separately. Results: The prognostic/predictive value of specific KRAS variants revealed differences in real-world outcomes (Table). OS was greater in pts with KRAS G12V and G12R variants, as was PFS on 5FU-Based Therapy (e.g. FOLFIRINOX) but not for Gemcitabine/nab-Paclitaxel. Opposing trends were noted for KRAS Q61. Pts with KRAS wild type tumors as well as both actionable subgroups also had an improved OS. Conclusions: In this large national dataset, we demonstrate that KRAS mutation status and specific variants appear to be prognostic as well as predictive in pancreatic cancer. [Table: see text]
Primary analysis of KAITLIN: A phase III study of trastuzumab emtansine (T-DM1) + pertuzumab versus trastuzumab + pertuzumab + taxane, after anthracyclines as adjuvant therapy for high-risk HER2-positive early breast cancer (EBC).
Authors: Harbeck Nadia , Im Seock-Ah , Barrios Carlos H. , Bonnefoi Herve R. , Gralow Julie , Toi Masakazu , Ellis Paul , Gianni Luca , Swain Sandra M. , Im Young-Hyuck , De Laurentiis Michelino , Nowecki Zbigniew , Shah Jigna , Boulet Thomas , Liu Haiying , Macharia Harrison , Trask Peter , Song Chunyan , Winer Eric P. , Krop Ian E. 
Published: May 2020

500 Background: The standard of care for HER2-positive EBC is chemotherapy plus one year of HER2-directed therapy. However, recurrence—particularly in high-risk populations—remains a problem, as does systemic chemotherapy-associated toxicity. In KAITLIN, we aimed to improve efficacy and reduce toxicity by replacing taxanes and trastuzumab with T-DM1. Methods: KAITLIN (NCT01966471) is a phase 3, randomized, open-label study that enrolled 1846 patients with adequately excised, centrally confirmed HER2-positive EBC either node-positive (LN+); or node-negative, HR-negative, and tumor size > 2.0 cm. Within 9 weeks of surgery, patients were randomized 1:1 to 3-4 cycles of anthracycline-based chemotherapy followed by 18 cycles of T-DM1 3.6 mg/kg + pertuzumab 420 mg q3w (loading dose [LD] 840 mg) (AC-KP) or taxane (3-4 cycles) + concurrent trastuzumab 6 mg/kg (LD 8 mg/kg) + pertuzumab 420 mg q3w (LD 840 mg) (AC-THP). Patients were stratified by world region, nodal status, HR status, and anthracycline type. Adjuvant radiotherapy and/or endocrine therapy was administered after 4 cycles of HER2-targeted therapy when indicated. The co-primary endpoints were invasive disease-free survival (IDFS) in the LN+ and in the ITT populations applying a hierarchical testing procedure. Secondary endpoints included overall survival (OS), patient-reported outcomes (PROs), and safety. Results: KAITLIN did not meet its co-primary endpoints. In LN+ patients (n = 1658), there was no significant difference between arms in IDFS event risk (stratified hazard ratio = 0.97; 95%CI 0.71–1.32). Three-year IDFS was 94.1% with AC-THP and 92.7% with AC-KP. Results were similar in the ITT population (stratified hazard ratio = 0.98; 95%CI 0.72–1.32; 3-year IDFS: 94.2% vs 93.1%). OS data are immature with an event rate of ~4%–5% in each arm. During the study overall, there was a similar incidence of grade ≥3 AEs (55.4% vs 51.8%) and SAEs (23.3% vs 21.4%) with AC-THP and AC-KP, respectively. More patients receiving AC-KP than AC-THP discontinued T-DM1 or trastuzumab, respectively, because of AEs (26.8% vs 4.0%). PRO data will be presented. Conclusions: Replacing adjuvant taxane and trastuzumab with T-DM1 did not result in significantly improved efficacy or overall safety. Nonetheless, in this high-risk population, a favorable IDFS outcome was achieved in both study arms. HP + chemotherapy remains the standard of care for patients with high-risk HER2-positive EBC. Clinical trial information: NCT01966471 .
Phase II trial of lenvatinib (LEN) plus pembrolizumab (PEMBRO) for disease progression after PD-1/PD-L1 immune checkpoint inhibitor (ICI) in metastatic clear cell renal cell carcinoma (mccRCC).
Authors: Lee Chung-Han , Shah Amishi Yogesh , Hsieh James J , Rao Arpit , Pinto Alvaro , Bilen Mehmet Asim , Cohn Allen Lee , Di Simone Christopher , Shaffer David R. , Girones Sarrio Regina , Gunnestad Ribe Sara , Wu Jane , Schmidt Emmett V. , Perini Rodolfo F. , Kubiak Peter , Smith Alan D. , Motzer Robert J. 
Published: May 2020

5008 Background: LEN, a multikinase VEGFR inhibitor, plus everolimus is approved for advanced RCC after prior VEGF-targeted therapy. PEMBRO, an anti-PD-1 antibody, plus axitinib is approved as first-line therapy of advanced RCC. We report phase 2 results of the RCC cohort of a phase 1b/2 trial (Study 111/KEYNOTE-146) of LEN + PEMBRO in patients (pts) who progressed after ICI therapy. Methods: We performed a multicenter, open-label study of pts with mccRCC, who previously had disease progression by RECIST (confirmed ≥ 4 weeks later) during or following ICI therapy. Pts had measurable disease by immune-related RECIST, and ≥ 1 prior therapy. Pts received LEN 20 mg orally once daily plus PEMBRO 200 mg IV every 3 weeks until disease progression or toxicity. Tumor assessments were performed every 6 weeks (until week 24), then every 9 weeks. The primary endpoint was objective response rate (ORR) at Week 24 by irRECIST. Results: 104 pts were enrolled. At data cutoff (January 12, 2020), 71 (69%) pts were still on study treatment. Most pts had ≥2 prior anticancer regimens (58%). 91 of 104 pts were evaluable for response at Week 12 (13 pts NE at Week 12); 46 of 91 pts achieved a confirmed partial response for an ORR of 51% (Table). Median progression-free survival (PFS) was 11.7 months and median duration of response (DOR) was 9.9 months. The most common treatment-related adverse events (TRAEs) were fatigue (49%), diarrhea (44%), proteinuria (37%), hypertension (31%), nausea (31%), dysphonia (29%), stomatitis (29%), and arthralgia (27%). There was 1 grade 5 TRAE (upper gastrointestinal hemorrhage). 43% of pts required dose reduction and 12% of pts discontinued treatment due to TRAEs. Response and safety data will be updated to include all pts evaluable at an April 9, 2020 cut-off. Conclusions: LEN + PEMBRO demonstrated promising antitumor activity in pts with mccRCC with disease progression following ICI therapy. No new safety signals were detected. Efficacy outcomes by investigator review per irRECIST. Clinical trial information: NCT02501096 . [Table: see text]
Thromboembolism (TE) in patients (pts) with bladder cancer treated with checkpoint inhibitors (CPIs).
Authors: Sheng Iris Yeong- Fung , Gupta Shilpa , Reddy Chandana A. , Angelini Dana E , Funchain Pauline , Sussman Tamara A. , Sleiman Joseph , Gilligan Timothy D. , Ornstein Moshe Chaim , Khorana Alok A. 
Published: May 2020

5042 Background: Most pts with bladder cancer will be treated with immunotherapy. There is concern for increased TE risk with CPIs in this already high risk population. We present the first analysis of the incidence and outcomes of venous (VTE) and arterial (ATE) thromboembolism in pts with bladder cancer treated with CPIs. Methods: Consecutive pts with bladder cancer treated with CPIs at the Cleveland Clinic from 1/2015 to 12/2019 were identified and TE events noted. Overall survival (OS) was estimated using Kaplan-Meier method and the impact of VTE on OS was evaluated using Cox proportional hazards regression. Results: Of 274 pts, 72% were men (median age 73.3 years, 89% white), 82% had pure UC, 92% had lower tract disease, and 67% had a Bajorin score ≥1 (median KPS 90, 61% visceral metastases), 59% had prior systemic therapy (median 1, range 0-4) and 36% had prior TE (14% ATE, 19% VTE, 0.4% both). At CPI initiation, 24% were on antiplatelet therapy, and 15% on therapeutic anticoagulation. CPI (median doses 5, range 8.5-59) included: 40% atezolizumab, 3% nivolumab, 57% pembrolizumab. VTE occurred in 14% (n = 37), including 8% DVT, 4% PE, 2% both. DVT locations were 56% lower limb, 26% upper limb, 15% visceral vein, 4% visceral+upper limb. 2% (n = 5) had ATE (1% CVA, 0.4% visceral, 0.4% left subclavian). 92% of VTE and all ATE occurred within 6 months of CPI initiation. The incidence of TE was 10.9% (95%CI 6.6%—15.1%) at 6 months and 19.8% (95%CI 13.3%-26.4%) at 12 months. 82% of VTE (mean 6 days) and all ATE (mean 5 days) resulted in hospitalization. Multivariate analysis showed TE (HR 2.296, 95%CI 1.451-3.632, p = 0.0004), Bajorin score 1 (HR 1.490, 95%CI 1.036-2.142, p = 0.0315), and Bajorin score 2 (HR 3.50, 95%CI 2.14-5.74, p < 0.0001) were independently associated with worse OS. Conclusions: CPIs in bladder cancer pts are associated with a high TE risk, especially within six months of initiation. TE is associated with worsened survival. Further investigation into the risk factors for CPI-associated TE is needed to identify if benefits exist from thromboprophylaxis.