tbuckley/cabot-search huggingface dataset:
Real-world characteristics and outcomes of patients with advanced non-small cell lung cancer (aNSCLC) receiving immune checkpoint inhibitor.
Authors: Sean Khozin, Jizu Zhi, Monika Jun, Li Chen, Wendy S. Rubinstein, Mark S. Walker, George Anthony Komatsoulis, Jeremy Roberts, Ryan Fukushima, Denise Lau, Brigham Hyde, Edward Stepanski, Robert S. Miller
Journal: Journal of Clinical Oncology (2019)

9110 Background: Immune Checkpoint Inhibitors (ICIs) were first approved for the treatment of aNSCLC in 2014, and since this time have seen rapid adoption in the marketplace. We sought to describe the characteristics of patients with aNSCLC receiving ICIs in the real-world, as well as to examine treatment patterns and outcomes in the time since initial ICI approval. Methods: We conducted a retrospective, observational cohort study using statistically de-identified data from January 2011 to November 2018 in CancerLinQ, ASCO’s real-world oncology database. Adult patients with a curated diagnosis of Stage III or IV NSCLC who received ≥1 dose of an ICI and had ≥2 clinical visits were eligible for inclusion. Stage III patients were excluded if they received any local therapy &lt; 1 year prior to receiving ICI. Patients were also excluded if they received ICI prior to the first FDA approval date. Demographic and clinical characteristics of aNSCLC patients receiving ICI are reported. Outcomes including time to treatment discontinuation (TTD), time to next treatment (TTNT), real-world progression free survival (rwPFS) and overall survival (OS) were examined via the Kaplan Meier method. Results: Among 2,425 aNSCLC ICI patients included in this analysis, median age was 68.0 years (IQR 60.7, 75.2], 54% were male and 73% of patients were white. Non-squamous histology accounted for 64% of aNSCLC ICI users, and 81% had Stage IV disease. Eastern Cooperative Oncology Group (ECOG) performance status was 0-1 in 77% and 2+ in 23% of patients, and 70% were current or former smokers. The majority (75%) of patients received ICI as second-line or later therapy. Treatment outcomes and survival are reported in the Table. Conclusions: This analysis demonstrates that aNSCLC patients receiving ICI therapy in the real-world are older than what was reported in some clinical trials, though survival outcomes were similar. Further research to examine impact of covariates on outcomes is warranted. [Table: see text]
Dual blockade of PD-1 and PD-L1 is effective but causes severe pneumonitis in lung metastasis: Syngeneic mice study for validation of clinical observation.
Authors: Yu-Jen Chen, Shin-Yi Liu, Hui-Ru Shieh, Chun-Chuan Ko, Hung-Chang Liu
Journal: Journal of Clinical Oncology (2019)

e14115 Background: In clinical practice, the shifting use of PD-1 inhibitors and its ligand PD-L1 inhibitors due to ineffectiveness or toxicity is becoming more common and has distinct responses. To validate clinical observation, we examined the anti-cancer effect, tumor microenvironment (TME) modulation and toxicity of dual blockade of PD-1 and PD-L1 in mice. Case Presentation: Three patients with metastatic lung adenocarcinoma received nivolumab (5, 5 and 11 doses); after the initial response and subsequent progression, they were shifted to receive atezolimumab (1, 1 and 4 doses) at intervals of 70, 38 and 43 days, respectively. All 3 patients obtained partial response according to iRECIST. Two of the 3 patients developed pneumonitis at days 3 and 15 after the first dose of atezolimumab and pneumonitis subsided by methylprednisolone injection for 7 and 4 days. Methods: The Balb/c mice bearing lung metastasis of CT26 colon cancer cells were treated. Assessments included optical imaging for tumor burden, multi-parameter flow cytometry for TME, pathology and immuohistochemistry. Results: The pathology of lung showed that all the mice (100%, n = 3 for each group) treated with a combination of anti-PD-1 and anti-PD-L1, either sequential or simultaneous, developed severe clustered inflammatory infiltrates, mucus filling in bronchus and thrombi in small vessels. Among infiltrating leukocytes, combinatorial blockade increased LyC6 + inflammatory monocytes and NKG2D + T cells and reduced tumor-associated macrophages in lung. Peripheral leukocytes in spleen had no such alteration. In lung metastatic foci, the expression of PD-1 was noted mainly within tumors, and this expression was reduced by combinatorial blockade. PD-L1 expression had no change. For control of lung metastasis, the combinatorial treatments exhibited better control, and anti-PD-L1 followed by anti-PD-1 was the most effective. No significant pneumonitis was noted in single blockade groups. Conclusions: The combination of PD-1 and PD-L1 blockade, either sequential or concurrent, may have better tumor control but cause severe pneumonitis. Dual blockade of PD-1 and PD-L1 should be used with caution.
Role of adjuvant chemotherapy in small (≤5 mm) node-negative and hormone receptor-negative breast cancer.
Authors: Samip R. Master, Neelakanta Dadi, Chintan Shah, Gary Von Burton, Runhua Shi
Journal: Journal of Clinical Oncology (2019)

e12021 Background: There is currently lack of adequate data to support for or against the role of adjuvant chemotherapy for small( &lt; = 5mm) hormone negative and node negative breast cancer. We did a retrospective analysis from National Cancer Database (NCDB) to assess the effect of adjuvant chemotherapy in HER2 positive/ Hormone receptor negative (HER+HR-) and triple negative breast cancer. Methods: Data was analyzed from approximately nine thousand women registered in the (NCDB) who were diagnosed with triple negative and HER+ HR-small ( &lt; = 5mm) and node negative breast cancer between 2010 and 2014 and had follow-up to the end of 2015. The primary predictor variable was the receipt of chemotherapy, and outcome variable was overall survival. Additional variables addressed and adjusted included age, race, Charlson Comorbidity Index and grade of cancer. Results: Approximately 59% patients received adjuvant chemotherapy. The five year overall survival in women with triple negative for breast cancer who received chemotherapy was 79% , compared to 87% , for those who did not receive chemotherapy(p &lt; 0.00001). The five year overall survival in women with Her2+HR- for breast cancer who received chemotherapy was 68% , compared to 84% , for those who did not receive chemotherapy(p &lt; 0.00001).In multivariate analysis, after adjusting for secondary predictor variables, avoidance of adjuvant chemotherapy was associated with 59.5% reduction in risk of death. Conclusions: Our analysis suggests that there are no role for adjuvant chemo in small breast cancers that are Her+ HR- and triple negative. The receipt of adjuvant chemotherapy lead to decrease in overall survival.
New genetic signals for lung function highlight pathways and chronic obstructive pulmonary disease associations across multiple ancestries
Authors: Nick Shrine, Anna L. Guyatt, A. Mesut Erzurumluoglu, Victoria E. Jackson, Brian D. Hobbs, Carl A. Melbourne, Chiara Batini, Katherine A. Fawcett, Kijoung Song, Phuwanat Sakornsakolpat, Xingnan Li, Ruth Boxall, Nicola F. Reeve, Ma’en Obeidat, Jing Hua Zhao, Matthias Wielscher, Stefan Weiss, Katherine A. Kentistou, James P. Cook, Benjamin B. Sun, Jian Zhou, Jennie Hui, Stefan Karrasch, Medea Imboden, Sarah E Harris, Jonathan Marten, Stefan Enroth, Shona M. Kerr, Ida Surakka, Veronique Vitart, Terho Lehtimäki, Richard J. Allen, Per S. Bakke, Terri H. Beaty, Eugene R. Bleecker, Yohan Bossé, Corry-Anke Brandsma, Zhengming Chen, James D. Crapo, John Danesh, Dawn L. DeMeo, Frank Dudbridge, Ralf Ewert, Christian Gieger, Amund Gulsvik, Anna L. Hansell, Ke Hao, Joshua D. Hoffman, John E. Hokanson, Georg Homuth, Peter K. Joshi, Philippe Joubert, Claudia Langenberg, Xuan Li, Liming Li, Kuang Lin, Lars Lind, Nicholas Locantore, Jian’an Luan, Anubha Mahajan, Joseph C. Maranville, Alison Murray, David C. Nickle, Richard Packer, Margaret M. Parker, Megan L. Paynton, David J. Porteous, Dmitry Prokopenko, Dandi Qiao, Rajesh Rawal, Heiko Runz, Ian Sayers, Don D Sin, Blair H Smith, María Soler Artigas, David Sparrow, Ruth Tal-Singer, Paul R. H. J. Timmers, Maarten Van den Berge, John C. Whittaker, Prescott G. Woodruff, Laura M. Yerges-Armstrong, Olga G. Troyanskaya, Olli T. Raitakari, Mika Kähönen, Ozren Polašek, Ulf Gyllensten, Igor Rudan, Ian J. Deary, Nicole M. Probst-Hensch, Holger Schulz, Alan L James, James F. Wilson, Beate Stubbe, Eleftheria Zeggini, Marjo-Riitta Jarvelin, Nick Wareham, Edwin K. Silverman, Caroline Hayward, Andrew P. Morris, Adam S. Butterworth, Robert A. Scott, Robin G. Walters, Deborah A. Meyers, Michael H. Cho, David P. Strachan, Ian P. Hall, Martin D. Tobin, Louise V. Wain
Journal: Nature Genetics (2019)
Triplet therapy (continuous ribociclib, everolimus, exemestane) in HR+/HER2− advanced breast cancer postprogression on a CDK4/6 inhibitor (TRINITI-1): Efficacy, safety, and biomarker results.
Authors: Aditya Bardia, Sara A. Hurvitz, Angela DeMichele, Amy Sanders Clark, Amelia Bruce Zelnak, Denise A. Yardley, Meghan Sri Karuturi, Tara B. Sanft, Sibel Blau, Lowell L. Hart, Cynthia X. Ma, Nicola Caria, D. Das Purkayastha, Alomi Mistry, Stacy L. Moulder
Journal: Journal of Clinical Oncology (2019)

1016 Background: The combination of CDK4/6 inhibitor (CDK4/6i) + endocrine therapy (ET) provides consistent improvement in PFS and response rates compared with single-agent ET as first- or subsequent-line therapy in HR+, HER2− advanced breast cancer (ABC), but the optimal regimen postCDK4/6i progression, including the role of continued CDK 4/6 blockade, is unclear. Methods: TRINITI-1 is a Phase I/II, open-label trial (NCT02732119) of triplet therapy: ribociclib (RIB; CDK4/6i) + everolimus (EVE; mTORi) + exemestane (EXE; ET) in men or postmenopausal women with HR+, HER2− ABC that progressed on prior CDK4/6i and up to 3 lines of therapy (≥ 1 ET and ≤ 1 chemotherapy regimen). Phase I determined RP2D; Phase II assessed efficacy/safety of RIB 300 or 200 mg + EVE 2.5 or 5 mg + EXE 25 mg/day. Here we present the first results in the entire patient population who received this triplet regimen and the correlation of biomarkers with outcomes. Results: As of October 24, 2018, 95 patients were evaluable (ET refractory and postCDK4/6i) in Phases I (n = 17) and II (n = 78). Continuous RIB + EVE + EXE demonstrated clinical benefit at week 24 in 39 patients (41.1%), exceeding the predefined primary end point threshold (&gt; 10%). ORR was 8.4% by investigator assessment, median PFS was 5.7 months, and 1-year PFS was 33%. AEs were consistent with known safety profile of RIB, EVE, and EXE. Most common AEs were neutropenia (all grades, 41.7%; grade 3/4, 31.3%), stomatitis (41.7%; 3.1%), and fatigue (35.4%; 1.0%). No grade 3/4 QTc prolongation was noted. ctDNA genotyping revealed patients with certain tumor alterations, eg ESR1, had shorter median PFS vs wild-type: 3.5 vs 6.9 mo (HR 1.76, 95% CI 1.01–3.05). Additional genomic results, including PIK3CA, will be presented. Conclusions: TRINITI-1 met its primary efficacy end point and is the first trial to demonstrate clinical benefit and tolerability of continuous triplet therapy with ET + mTORi + CDK4/6i in patients with ET-refractory HR+, HER2− ABC postCDK4/6i progression. Tumor genomic profile might impact the clinical outcome with triplet therapy and warrants additional research to guide rational therapy selection. Clinical trial information: NCT02732119.
Efficacy and safety of PD-1/PD-L1 inhibitors plus nab-paclitaxel with or without bevacizumab as second-line therapy or beyond for patients with metastatic non-small-cell lung cancer.
Authors: Fan Zhang, Tao Li, Yuzi Zhang, Shangli Cai, Lei Zhao, Shun Chang Jiao, Yi Hu
Journal: Journal of Clinical Oncology (2019)

e20517 Background: Immunotherapy combined with platinum-based chemotherapy is now standard first line treatment for NSCLC patients. However, limited evidence exists to show the efficacy of immunotherapy plus taxanes for patients who have progressed after platinum-based chemotherapy. Therefore, a retrospective study was conducted to assess whether immunotherapy plus nab-paclitaxel with or without bevacizumb could improve efficacy compared with immune monotherapy as second line therapy or beyond for NSCLC patients. Methods: Patients with metastatic NSCLC receiving anti-PD-1/PD-L1 monotherapy or combination therapy from 2015 to 2018 were identified in Chinese People’s Liberation Army General Hospital. Patients who received PD-1/PD-L1 inhibitors as first-line therapy or combined with therapies other than nab-paclitaxel and bevacizumab were excluded. The primary endpoint was progression-free survival (PFS). Secondary endpoints were objective response rate (ORR), disease control rate (DCR) and safety. Results: Of 59 patients, 42 were treated with anti-PD-1/PD-L1 monotherapy and 17 were treated with anti-PD-1/PD-L1 plus nab-paclitaxel with or without bevacizumab. With a median follow-up of 8.2 months, combination therapy group showed significantly longer PFS compared with monotherapy group (8.4m vs. 3.7m, P = 0.047). When adjusted by covariates in COX proportional regression model, both treatment group (P = 0.007, Hazard ration [HR] 0.32; 95%CI 0.14-0.73) and performance status (P = 0.018, HR 0.44; 95%CI 0.22-0.87) demonstrated significant contribution to longer PFS. In addition, ORR was 23.5% (4/17) in the combination therapy group versus 12.8% (5/39) in the monotherapy group (P = 0.265) and the DCR was 88.2% (15/17) in the combination therapy group versus 61.5% (24/39) in the monotherapy group (P = 0.061). The incidence of grade 3/4 adverse events were 23.5% (4/17) in the combination therapy group and 4.8% (2/42) in monotherapy group (P = 0.052). Conclusions: PD-1/PD-L1 inhibitor plus nab-paclitaxel with or without bevacizumab resulted in significantly longer PFS and higher DCR as second line therapy of beyond in metastatic NSCLC patients. These findings need to be further explored by randomized controlled studies.
Single-arm phase I/II study of the safety and efficacy of OncoTherad immunomodulator in patients BCG-refractory or relapsed non-muscle invasive bladder cancer.
Authors: Wagner José Fávaro, Sonia Regina Iantas, Juliana Mattoso Gonçalves, Eduardo Augusto Rabelo Socca, Nelson Duran, Athanase Billis, João Carlos Cardoso Alonso
Journal: Journal of Clinical Oncology (2019)

e16000 Background: There is no effective intravesical second-line therapy for high-grade non-muscle-invasive bladder cancer (HGNMIBC) when Bacillus Calmette-Guerin (BCG) fails. In this scenario, a new perspective is represented by OncoTherad immunomodulator. OncoTherad is a nanostructured inorganic phosphate complex associated to glycosidic protein, developed by University of Campinas/ Brazil, which exhibits antitumor properties. The aims of the study were to evaluate the efficacy and safety of OncoTherad immunomodulator for BCG-refractory or relapsed HGNMIBC. Methods: We carried out a prospective, single-center (Municipal Hospital of Paulinia, São Paulo, Brazil), single-arm phase I/II study in 15 (10 male, 5 female) consecutive patients with HGNMIBC-refractory or relapsed (≥ 1 previous course of BCG intravesical therapy). Patients with muscle-invasive disease were excluded. OncoTherad regimen consisted of an induction course of 6 weekly intravesical instillations followed by a maintenance course of 1 monthly instillation until completing 1 year of treatment. Follow-up was performed with systematic mapping biopsies of the bladder, cystoscopy, ultrasound and urinary cytology. The primary endpoint was recurrence-free survival (RFS) rate, and secondary endpoint was safety response. The recurrence was defined as histology proven tumor recurrence (any grade), and monitored at 3-month intervals. Results: The median age and follow-up were 71 years and 14.0 months, respectively. A 14-months RFS rate in all patients was 86.7%. Only 2 patients (13.3%) showed recurrence during follow-up, however these patients showed incipient malignant lesions (downstaging of pT1G3 to pTaG1). Regarding toxicity, we reported moderate adverse systemic event of hypersensitivity to OncoTherad in 2 patients (13.3%), and minimal local side effects (dysuria and cystitis)in 6 patients (40.0%). Conclusions: In conclusion, OncoTherad seems a safe and effective treatment option for BCG-refractory or relapsed HGNMIBC patients and may provide benefit for preventing tumor recurrence. We report a RFS rate of 86.7% (14.0 months), potentially avoiding or postponing the need for radical surgery in these patients. Clinical trial information: CAAE: 93619718.7.0000.5404.
Abstract 2878: Feasibility of Post-Mortem Device Interrogation for Detection of Terminal Arrhythmias and/or Device Failure
Authors: Brian Mendelson, James Kirkpatrick, Leslie Litzky, Ralph Verdino
Journal: Circulation (2009)

Introduction: Pacemaker (PM) and ICD failures have been reported at alarming rates and implicated in pt deaths, yet the frequency of association with mortality remains unknown. Device investigation...
Trends in financial relationships between industry and individual medical oncologists in the United States from 2014 to 2017: A cohort study.
Authors: Deborah Catherine Marshall, Elizabeth Stieglitz Tarras, Kenneth Rosenzweig, Deborah Korenstein, Susan Chimonas
Journal: Journal of Clinical Oncology (2019)

6520 Background: Industry-physician financial relationships in medical oncology are common and introduce conflicts of interest. The Open Payments (OP) program collects and discloses data on industry payments to physicians, in part to discourage inappropriate relationships. However, the effect of OP on how oncologists engage with industry is unknown. Our aim was to evaluate trends in physician-level payments to test whether the implementation of OP has resulted in fewer physicians engaging with industry and has shifted the nature of interactions towards those considered more appropriate. Methods: We performed a retrospective cohort study of US medical oncologists in 2014 from the National Plan and Provider Enumeration System. OP data for general (non-research) payments between 2014-2017 were matched to physician to evaluate receipt of payments over time. We calculated the percentage of physicians receiving payments, annual value and number of payments, and average annual trends over time, including by nature of payment. Results: From 2014-2017, medical oncologists received 1.4 million industry payments totaling $330.6 million. The absolute number of medical oncologists receiving payments decreased 4% on average annually ( P= .006), and proportionally from 67.2% to 59.6% overall. The value and number of payments have not significantly changed. The value and number of payments increased for accredited/certified CME (+821% and +209% annually) and decreased for non-accredited/certified CME (-18% and -25% annually). The value and number of food/beverage payments remained the same. The value and number of royalty/licensing payments increased. Conclusions: Fewer oncologists are receiving payments, but spending has not decreased suggesting that physicians are less likely to engage and industry is more selective. Increased payments for accredited CME suggest that less appropriate speaker’s fees are being avoided. Food/beverage payments are not decreasing, thus these interactions may not be recognized as problematic. Increasing royalty/licensing payments require ongoing scrutiny. Changes in physician payments since the inception of OP highlight the importance of transparency in policymaking.
Abstract 11702: Vascular Function is Impaired in Subjects With Decreased Circulating Level of Pigment Epithelium-derived Factor
Authors: Masato Kajikawa, Yukihito Higashi, Tatsuya Maruhashi, Shinji Kishimoto, Shogo Matsui, Farina B Yusoff, Takayuki Hidaka, Kensuke Noma, Ayumu Nakashima, Takanori Matsui, Sho-ichi Yamagishi, Yasuki Kihara
Journal: Circulation (2017)

Introduction: Pigment epithelium-derived factor (PEDF) is a glycoprotein that belongs to the superfamily of serine protease inhibitors. It has been shown that PEDF plays a protective role against atherosclerosis. Several investigators have reported that serum levels of PEDF are increased in subjects with cardiovascular risk factors. However, the role of PEDF in cardiovascular disease is still controversial. The aim of this study was to evaluate the associations between serum levels of PEDF and vascular function and structure. Methods: We measured serum levels of PEDF, assessed vascular function by measurements of flow-mediated vasodilation (FMD) and nitroglycerine-induced vasodilation in the brachial artery, and measured brachial artery intima-media thickness (IMT) in 150 subjects who underwent health examinations, including subjects with cardiovascular disease. We investigated cross-sectional associations between serum levels of PEDF and vascular function and structure. Results: Univariate regression ana...
Pembrolizumab versus placebo as adjuvant therapy in resected high-risk stage II melanoma: Phase 3 KEYNOTE-716 study.
Authors: Matteo S. Carlino, Paolo Antonio Ascierto, Alexander M. Eggermont, Jeffrey E. Gershenwald, Jean Jacques Grob, Axel Hauschild, John M. Kirkwood, Georgina V. Long, Peter Mohr, Caroline Robert, Merrick I. Ross, Richard A. Scolyer, Vernon K. Sondak, Charles Yoon, Andrew Stewart Poklepovic, Piotr Rutkowski, James R. Anderson, Sama Ahsan, Nageatte Ibrahim, Jason J. Luke
Journal: Journal of Clinical Oncology (2019)

TPS9596 Background: Adjuvant pembrolizumab showed significantly longer recurrence-free survival than placebo in patients with resected stage III melanoma in the KEYNOTE-054 study. KEYNOTE-716 (NCT03553836) is a randomized, placebo-controlled, double-blind, multicenter phase 3 study of adjuvant pembrolizumab in patients with surgically resected high-risk stage II melanoma. Methods: Key eligibility criteria are age ≥12 y with newly diagnosed, completely resected stage IIB/IIC cutaneous melanoma, defined by the AJCC Cancer Staging Manual, 8th edition (wide excision and negative sentinel lymph node biopsy with no evidence of distant metastasis). Patients with mucosal or uveal melanoma or prior treatment (including radiation) for melanoma beyond resection of primary disease within 12 wk of the start of study treatment were excluded. In this 2-part study, in the double-blind phase (part 1), patients will be randomly assigned 1:1 to receive pembrolizumab 200 mg for patients ≥18 y or 2 mg/kg for patients ≥12 y to &lt; 18 y (maximum dose, 200 mg) or placebo every 3 wk for 17 cycles. Study treatment will begin within 12 wk of complete resection. Tumor imaging will be performed every 24 wk while treatment is ongoing, at the end of treatment, every 6 mo for the first 3 y off treatment, and then yearly for up to 2 y or until recurrence (up to 5 y of total imaging). Adverse events will be recorded until 30 d after treatment end (90 d for serious AEs) and graded per National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0. In the unblinded phase (part 2), patients with confirmed recurrence may be rechallenged (patients received pembrolizumab in part 1) or crossed over to pembrolizumab (patients received placebo in part 1). Resected local or distant recurrence or unresectable disease will be treated for an additional 17 or 35 cycles, respectively. Tumor imaging in part 2 will occur every 12 wk during treatment. The primary end point is recurrence-free survival; secondary end points are distant metastasis-free survival, overall survival, and safety. Approximately 954 patients will be enrolled. Clinical trial information: NCT03553836.