tbuckley/cabot-search huggingface dataset:
Recombinant humanized anti-PD-1 monoclonal antibody (JS001) in patients with refractory/metastatic nasopharyngeal carcinoma: Interim results of an open-label phase II clinical study.
Authors: Fenghua Wang, Xiao-Li Wei, Ji Feng Feng, Qi Li, Nong Xu, Xi-Chun Hu, Yi Jiang, Wangjun Liao, Qingyuan Zhang, Xianglin Yuan, Haixin Huang, Ye Chen, Guanghai Dai, Jianhua Shi, Lin Shen, Shujun Yang, Yongqian Shu, Yunpeng Liu, Rui-hua Xu
Journal: Journal of Clinical Oncology (2019)

6017 Background: Metastatic nasopharyngeal cancer (NPC) patients progressed afterstandardtherapy have limited treatment options. Toripalimab, also known as JS001, a humanized IgG4 antibody specific for human PD-1, has been approved for 2 nd line treatment of metastatic melanoma in China. Here we report the results from a phase IIstudy in metastatic NPC patients treated with toripalimab.(Clinical trial ID: NCT02915432). Methods: This multi-center, open-label, phase II registration study is designed to evaluate the safety and efficacy of toripalimab in metastaticNPC patients who have failed systemic treatment. Toripalimabis given at 3 mg/kg IV Q2W until disease progression or intolerable toxicity.Tumor PD-L1 expression, plasma EBV DNA level and other biomarkerswill be correlatedwith clinical response. Results: Enrollment of 190chemo-refractory metastatic NPCpatients was completed by Feb 2019 from 17 participating centers. The median age was 46 years, with 89.5% patients received at least 2 lines of prior systemic therapies. Treatment related adverse events (TRAE)occurred in 92% patients, which were mostly grade 1 or 2.Common TRAE includedanemia, hypothyroidism, AST increased, proteinuria, pyrexia, cough, constipation, ALT increased, hypoalbuminemia and pruritus.Grade 3 or higherTRAEoccurred in 25% patients.By the cut-off date of Jan 7 2019, among 135 evaluable patients, 3 complete responses, 31 partial responses and 40 stable diseaseswere observed for an objective response rate (ORR) of 25.2% and a disease control rate of 54.8%. PD-L1 expression results were obtained from 125 patients and 45.6% (57/125) were PD-L1+.PD-L1+ patientsachieved slightly higherORR than PD-L1- patients, 29.8% versus 22.1%. In addition, an average drop of 47-fold plasma EBV DNA copy number was observed in responding patients, which typically proceeded the radiographic identification of clinical benefit. Conclusions: Toripalimab has demonstrated a manageable safety profileand encouraging clinical activity in the largest check-point blockade study in NPC to date. A change in plasma EBV DNA copy number might serve as a predictive marker for favorable clinical response. Patients will be continuously monitored for additional safety and survival readouts. Clinical trial information: NCT02915432.
Out of pocket costs and financial toxicity experienced by patients in early phase clinical trials.
Authors: Ryan Huey, Goldy George, Penny Phillips, Revenda White, Siqing Fu, Filip Janku, Daniel D. Karp, Aung Naing, Sarina Anne Piha-Paul, Vivek Subbiah, Apostolia Maria Tsimberidou, Shubham Pant, Timothy A Yap, Jordi Rodon Ahnert, Funda Meric-Bernstam, Ya-Chen T. Shih, David S. Hong
Journal: Journal of Clinical Oncology (2019)

e18383 Background: Clinical trials are an important therapeutic option for cancer patients. Although financial burden in cancer treatment is well-described, the financial burden associated with clinical trials is not well understood, especially for patients with lower socioeconomic status. Methods: We conducted a survey regarding economic burden and financial toxicity among cancer patients on Phase I clinical trials for at least 1 month. Financial Toxicity Score (FTS) was assessed using the validated COmprehensive Score for Financial Toxicity (COST) survey (scale 0-44, lower scores indicating worse financial toxicity). Patients also reported monthly out of pocket (OOP) medical and non-medical expenses. Results: Of 147 consecutive patients approached, 105 agreed to participate; median age = 60y; 62% female; 49% had annual income &lt; $60K; 50% lived &lt; 300 miles from the clinic; 34% required air travel; 41% had Medicare, 50% had employer sponsored insurance. Median FTS = 20, with interquartile range of 12.5. Median monthly OOP costs for non-medical expenses was $985, and for medical expenses was $475. Median total monthly OOP costs was $1695. Compared to patients in the highest quartile of FTS, a significantly lower % of patients in the lowest (worst) quartile of FTS had incomes &gt; $60K (27% v. 77%, P &lt; 0.001), and a significantly higher % were unemployed or not working outside the home (54% v. 12%, P = 0.001), and incurred higher than expected medical (39% vs. 12%, P = 0.025) and non-medical (64% vs. 15%, P = 0.003) expenses. Compared with patients for whom medical costs were not much higher than expected, a significantly higher % of patients with medical costs much higher than expected were non-White (77% v. 46%, P = 0.004) and unemployed/not working outside the home (46% v. 19%, P = 0.009). Conclusions: Among cancer patients participating on clinical trials, economic burden is high and financial toxicity is disproportionally higher in patients with lower income. OOP costs can be substantial and are often unexpected for patients.
Health care utilization associated with adverse events (AEs) among metastatic non-small cell lung cancer (mNSCLC) patients treated with immunotherapy or chemotherapy.
Authors: Nicole Engel-Nitz, Kellie Ryan, Michael P Johnson, Scott Bunner
Journal: Journal of Clinical Oncology (2019)

e20655 Background: Chemotherapy and immunotherapy (IO) are associated with increased overall survival in patients with mNSCLC, yet real-world data on AE-associated healthcare utilization are sparse. This study assessed incidence and utilization associated with AEs among patients initiating first-line treatment for mNSCLC with IO, IO with chemotherapy (IC), or chemotherapy alone (CH). Methods: Data were claims from commercial and Medicare Advantage patients (Jan 2008-Feb 2018). Inclusion criteria were mNSCLC, health plan enrollment for ≥6 months pre- (baseline) and ≥1 month post-index date; initiation of recommended systemic therapy for mNSCLC. Excluded were targeted or small-cell lung cancer therapy, and baseline surgery or other systemic therapy. AE incidence and healthcare utilization were measured from start of 1st line therapy until earliest of start of 2 nd line therapy or 180 days. AEs evaluated included hematologic, GI, endocrine, infections, infusion reactions, muscle, neurological, and respiratory. Results: Cohorts were 8,818 CH, 482 IO, and 412 IC. Mean age was older for IO (72 yrs, vs. 69 IC, 68 CH; P &lt; 0.001). IOs used were atezolizumab (n = 12), nivolumab (n = 148), and pembrolizumab (n = 673). Common chemotherapies were carboplatin (74%), pemetrexed (30%), and paclitaxel or etoposide (22%). Overall, 74% had ≥1 AE; incidence rate ratios (IRR) vs. IO (95% CI) were IC 1.36 (1.15-1.60) and CH 1.43 (1.28-1.61). Frequent AEs were blood conditions (43%), GI (32%), and infections (29%). IRR vs. IO included infections (1.94 CH), GI (1.71 IC, 1.90 CH), anemia (4.05 IC, 5.68 CH), leukopenia (5.69 IC, 22.28 CH), and thrombocytopenia (3.70 CH). CH had lower rates vs. IO for hyperthyroidism (2% IO; IRR 0.16 CH) and hypothyroidism (12% IO; IRR 0.19 CH). AE overlaps with infection were common; 61% of patients with infection had a hospitalization that involved both infection and another AE. AE-associated visits varied by cohort; ambulatory: 46% (IO), 50% IC, 61% CH; ER: 25% IO, 27% IC, 30% CH; inpatient: 29% IO, 35% IC, 37% CH (P &lt; 0.05 for all CH vs IO). Conclusions: AE-associated visits in mNSCLC were lower for IO-treated than for CH or IC-treated patients.
Disparities in the receipt of palliative care (PC) in metastatic renal cell carcinoma (mRCC).
Authors: Sri Harsha Tella, Anuhya Kommalapati, Pavan Kumar Tandra
Journal: Journal of Clinical Oncology (2019)

e18108 Background: Early integration of PC has shown to improve quality of life and survival in some solid malignancies. In this study we sought to analyze the PC utilization in mRCC patients. Methods: Patients with mRCC reported to NCDB between 2004 &amp; 2015 were extracted and we included the patients who died of mRCC. We classified the patients into three cohorts based on their length of survival ( &lt; 6, 6-24, and &gt; 24 months) to account for disease severity. Using SPSS, we performed multivariable logistic regression to determine the patient and institutional factors determining the PC use. Results: A total of 29,296 patients were analyzed. Overall, 20% (n = 5737) of the patients received PC. Among these, 7%,17%,7%, 53%, and 12% received pain management PC; palliative chemotherapy, surgery, radiation and combination therapies, respectively. On cox multivariate analysis, among patients that survived &lt; 6 months, receipt of PC was associated with better overall survival (OS) [HR: 0.91 (CI:0.87-0.95), p &lt; 0.01]. Patients who received PC were more likely to be of White race, non-Hispanic origin, treated at non-academic facilities, and had higher educational background (p &lt; 0.01) (Table). Patients living in East, Central, and Mountain regions had higher odds of receiving PC than those in the Pacific coast. The odds of receiving PC were significantly higher in patients who survived for &lt; 6 months as compared to that of &gt; 24 months (23 vs 13%, p &lt; 0.01). Conclusions: We noticed a significantly better OS in mRCC patients who received PC. Despite the benefits in OS and guidelines advocating the PC use, the overall PC utilization in mRCC is markedly low and plagued by race, facility type and geographic region. [Table: see text]
Association of detection of aflatoxin in plasma of Kenyan women with increased detection of oncogenic HPV.
Authors: Jianjun Zhiang, Elkanah Omenge, Titus Maina, Kapten Muthoka, Stephen Kiptoo, John Groopman, Yan Tong, Aaron Ermel, Patrick J. Loehrer, Darron Brown
Journal: Journal of Clinical Oncology (2019)

5530 Background: Cervical cancer is the leading cause of cancer-related deaths among women living in Africa. Only a small proportion of HPV-infected women develop cervical cancer and other cofactors may increase a woman’s risk of developing cervical cancer. Aflatoxin, a potent carcinogen and immunosuppressive agent, is produced by fungi that contaminate corn and other staple foods in sub-Saharan Africa. Women who ingest aflatoxin may be more likely to have persistent infections with oncogenic HPV type. Methods: Demographics, behavioral data, plasma, and cervical swabs were collected from HIV-uninfected women 18 and 45 years of age who presented for cervical cancer screening at Moi Referral and Teaching Hospital (Eldoret, Kenya) and had normal VIA examination. HPV testing was performed on cervical swabs using the Roche Linear Array Assay. Aflatoxin-albumin adduct (AFB1-lys) was detected and quantified in plasma. The association of plasma AFB1-lys detection and concentration and the detection of HPV was examined. Results: Sufficient plasma was available from 88 HIV-uninfected women and was transported to the U.S. for aflatoxin testing. Valid HPV testing results were available for 86 of these women (mean age 34.0 years); 49 women (57.0%) had detectable AFB1-lys and 37 (43.0%) had no detection. Substantial variation existed in plasma AFB1-lys concentrations among the 49 women (range 0.02 to 0.21 pg/µL). Detection of AFB1-lys was not associated with age, and other behavioral factors such as number of lifetime partners, marital status and age at first sex. AFB1-lys detection was associated with detection of A9 HPV types (HPV 16, 31, 33, 35, 52, and 58) as a group in cervical swabs (p = 0.029) as well as A9 types excluding HPV 16 (p = 0.020), but not with individual A9 types, A7 HPV types (such as HPV 18), or low-risk HPV types. A concentration dependent association of AFB1-lys was seen with detection of A9 HPV types as a group (p = 0.009), non-HPV 16 A9 types (p = 0.005), and HPV 52 (p = 0.042), but not with the A7 HPV types. Conclusions: AFB1-lys was detected in 57% of HIV-uninfected Kenyan women without cervical dysplasia. AFB1-lys-positive women were more likely than AFB1-lys-negative women to have oncogenic HPV A9 types detected. Higher plasma AFB1-lys concentrations were associated with increased likelihood of oncogenic HPV A9 type detection. Further studies are needed to determine if chronic exposure to aflatoxin interacts with HPV infection (and possibly HIV co-infection) to modulate the risk of cervical cancer in women in Kenya and other developing countries.
FRI0062 INFECTIONS AMONG RHEUMATOID ARTHRITIS PATIENTS STARTING OR SWITCHING BIOLOGICAL AGENTS. A SYSTEMATIC LITERATURE REVIEW
Authors: Marta Novella-Navarro, Alejandro Gomez-Gomez, Maria Auxiliadora Martin-Martinez, Mercedes Guerra-Rodriguez, Enrique Raya
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> The increased rate of infections is one of the most relevant issues regarding biologic therapies in Rheumatoid Arthritis (RA). There is a large number of studies comparing different biologic agents and biologic vs synthetic DMARDs in order to assess their safety profile. Nevertheless, the main question is whether biologics really increase the infection risk by themselves. Up to date, different studies tried to clarify the actual role that these drugs have in this potentially serious adverse effect, searching for other predisposing conditions related to patient clinical characteristics. <h3>Objectives</h3> To compare the risk of infections between patients starting biologic for the first time (naïve) and patients with an inadequate response to a previous biologic agent (switchers) <h3>Methods</h3> A search strategy was performed by the Spanish Society of Rheumatology documentalist over Pubmed, Embase and Cochrane Library databases (from January 2008 to February 2018). All the references retrieved were managed using Endnote X7®. Screening of studies, data collection and data analysis was performed by 2 reviewers. Meta-analysis, systematic reviews of Randomized Controlled Trials (RCT), Clinical Trials or Cohort studies, comparing data from adult RA patients starting biologics and switching biologics, were selected. After the first screening, a critical review was performed using electronic FLC platform for critical appraisal tools (Osteba®) and The Scottish Intercollegiate Guidelines Network (SIGN) was considered to classify the scientific evidence of the selected studies. Studies including patients with chronic infections, tuberculosis reactivations or surgical infections were excluded. <h3>Results</h3> 8 studies were included: 1RCT, 2 Open label study, 1 Open label extension from RCT, 2 subgroups analysis from RCTs and 2 prospective cohort studies. Overall infection rate was higher in switchers than in naïve patients, with a mean variation between 0-9 and 1.8 100 PY, serious infections were also higher in switchers patients, 2.2 100PY. In both groups, (naïve and switchers), patients treated with more cumulative dose of glucocorticoids (GC) had an increased risk of infections, and it was higher in patients with an inadequate response to previous biologic agents. Mean disease duration was longer in switchers, but this fact was not related to increase of infections. <h3>Conclusion</h3> This systematic review show that overall rate of infections is slightly higher in switchers than in naïve patients, but the fact of having received several biologic agents does not present itself as a risk factor for infection. However, the most important risk factor in the development infections was the higher cumulative doses of GC. <h3> Disclosure of Interests</h3> None declared
Meta-analysis in metastatic uveal melanoma to determine progression free and overall survival benchmarks: an international rare cancers initiative (IRCI) ocular melanoma study
Authors: L. Khoja, E.G. Atenafu, S. Suciu, S. Leyvraz, T. Sato, E. Marshall, U. Keilholz, L. Zimmer, S.P. Patel, S. Piperno-Neumann, J. Piulats, T.T. Kivelä, C. Pfoehler, S. Bhatia, P. Huppert, L.B.J. Van Iersel, I.J.M. De Vries, N. Penel, T. Vogl, T. Cheng, G. Fiorentini, F. Mouriaux, A. Tarhini, P.M. Patel, R. Carvajal, A.M. Joshua
Journal: Annals of Oncology (2019)
Combinational strategies of immunotherapy for hepatocellular carcinoma: One institutional experience in Taiwan.
Authors: Jo-Pai Chen, Fu-Jen Hsueh, Wei-Chen Lu, Wei-li Ma, Hsu Wu, Sung Hsin Kuo
Journal: Journal of Clinical Oncology (2019)

e15684 Background: Nivolumab in CheckMate40 study for advanced HCC has brought ORR 15 to 20% and DCR 55%. Our goup found lymph node or lung metastasis responded better and increased PDL1 expression in tumor-infiltrating immune cells after sorafenib (by Lu in AACR &amp; Liver Cancer 2018), suggesting sequential or combination use of sorafenib and immunotherapy. In the 1 st line setting, bevacizumab and atezolizumab has brought encouraging response, even with extrahepatic spread and/or macrovascular invasion. Methods: From early 2016 till now, 28 advanced HCC patients had received immunotherapy-containing regimens in Yun-Lin Branch of National Taiwan University Hospital. We have reviewed basic characteristics and regimens to find out their outcomes and responders characters. Results: In 28 patients (1 sorafenib-naive); 14 hepatitis B &amp; 10 hepatitis C; intrahepatic lesions only 25%, lymph node and/or lung metastasis 11%, fulminant spread 64%. The ORR was 25% and DCR was 53.6%. In 5 pembrolizumab users, 1 stable disease; 2 with 200 mg &amp; 3 with 2 mg/kg triweekly; 1(hepatitis B with fulminant metastasis) to fatal liver rupture after bevacizumab and pembrolizumab. In 23 nivolumab users, ORR was 30%; dosage ranging from 0.3 to 3 mg/kg (56.5%) biweekly; 16 combined with metronomic chemotherapy, 10 with bevacizumab, 10 with chemotherap, 7 with bevacizumab and chemotherapy; 1 (failing sorafenib, TACE, &amp; regorafenib) experienced liver necrosis to fatal liver failure after bevacizumab and nivolumab. 7 patients with partial response. Conclusions: In our institution, nivolumab combined with metronomic chemotherapy, low dose bevacizumab or sorafenib, or chemotherapy and even several combination regimens could produce favorable benefits and toxicity profiles in advanced HCCs regardless of viral etiology, even in heavily-treated and fulminant status. Possible combinational strategies of immunotherapy need to be developed with more rationales and biomarkers investigation.[Table: see text]
Scale-up of radiotherapy for cervical cancer in the era of human papillomavirus vaccination in low-income and middle-income countries: a model-based analysis of need and economic impact
Authors: Danielle Rodin, Emily A Burger, Rifat Atun, Michael Barton, Mary Gospodarowicz, Surbhi Grover, Timothy P Hanna, David A Jaffray, Felicia M Knaul, Yolande Lievens, Eduardo Zubizarreta, Michael Milosevic
Journal: The Lancet Oncology (2019)
Reprogrammed marrow adipocytes contribute to myeloma-induced bone disease
Authors: Huan Liu, Jin He, Su Pin Koh, Yuping Zhong, Zhiqiang Liu, Zhiqiang Wang, Yujin Zhang, Zongwei Li, Bjorn T. Tam, Pei Lin, Min Xiao, Ken H. Young, Behrang Amini, Michael W. Starbuck, Hans C. Lee, Nora M. Navone, Richard E. Davis, Qiang Tong, P. Leif Bergsagel, Jian Hou, Qing Yi, Robert Z. Orlowski, Robert F. Gagel, Jing Yang
Journal: Science Translational Medicine (2019)

Osteolytic lesions in multiple myeloma are caused by osteoclast-mediated bone resorption and reduced bone formation. A unique feature of myeloma is a failure of bone healing after successful treatment. We observed adipocytes on trabecular bone near the resorbed area in successfully treated patients. Normal marrow adipocytes, when cocultured with myeloma cells, were reprogrammed and produced adipokines that activate osteoclastogenesis and suppress osteoblastogenesis. These adipocytes have reduced expression of peroxisome proliferator-activated receptor γ (PPARγ) mediated by recruitment of polycomb repressive complex 2 (PRC2), which modifies PPARγ promoter methylation at trimethyl lysine-27 histone H3. We confirmed the importance of methylation in the PPARγ promoter by demonstrating that adipocyte-specific knockout of EZH2, a member of the PRC2, prevents adipocyte reprogramming and reverses bone changes in a mouse model. We validated the strong correlation between the frequency of bone lesions and the expression of EZH2 in marrow adipocytes from patients in remission. These results define a role for adipocytes in genesis of myeloma-associated bone disease and that reversal of adipocyte reprogramming has therapeutic implications.
A phase I, first-in-human, open label, dose-escalation and cohort expansion study of MGD019, a bispecific DART protein binding PD-1 and CTLA-4 in patients with unresectable or metastatic neoplasms.
Authors: Jason J. Luke, Manish Sharma, Rachel E. Sanborn, Gregory Michael Cote, Johanna C. Bendell, Glen J. Weiss, Alexey Berezhnoy, Sharad Sharma, Paul A. Moore, Ezio Bonvini, Kerri Cali, Jan E. Baughman, Jon M. Wigginton, Brad Sumrow
Journal: Journal of Clinical Oncology (2019)

TPS2661 Background: Immune checkpoint molecules, including CTLA-4 and PD-1, attenuate the duration and strength of adaptive immune responses to limit immune-mediated tissue damage. Tumors may inhibit cellular immune activation by expressing ligands that bind checkpoint molecules and inhibit T-cell function in the tumor microenvironment. Blockade of these inhibitory pathways is the primary mechanism of action of several novel cancer immunotherapy agents. Combined blockade of PD-1 and CTLA-4 with two checkpoint inhibitors, ipilimumab and nivolumab, increases antitumor activity beyond either single agent alone in patients with metastatic melanoma or other malignancies. MGD019, a novel bispecific molecule that co-engages and coordinately inhibits both PD-1 and CTLA-4 signaling, was developed to potentially improve antitumor activity and/or safety relative to the monoclonal antibody combination. MGD019 is an Fc-bearing tetravalent DART molecule (bivalent for each antigen) that can independently block either checkpoint molecule, with preferential co-blockade in cells co-expressing both molecules demonstrated in vitro. It is hypothesized that MGD019 might be clinically active in either checkpoint naïve or checkpoint experienced patients after prior PD-1/PD-L1 inhibitors. Methods: This Phase 1 study will characterize safety, dose limiting toxicities, and maximum tolerated dose (MTD)/maximum administered dose (MAD) of MGD019. Dose Escalation will enroll patients with advanced solid tumors of any histology in sequential escalating doses in cohorts of 3 to 9 patients in a 3+3+3 design. Once the MTD/MAD is reached, a Cohort Expansion phase will characterize safety and initial antitumor activity per RECIST v1.1 and irRECIST in patients with specific tumor types anticipated to be sensitive to dual checkpoint blockade. Additional endpoints include pharmacokinetics; immunogenicity; impact of MGD019 on various measures of immune-regulatory effects in peripheral blood and biopsy specimens; and relationship between antitumor activity and gene profiles, tumor mutational burden, and PD-1, PD-L1, and CTLA-4 expression on tumor cells and immune cell infiltrates within biopsy specimens. Patients will be followed for survival approximately every 3 months for 2 years. Clinical trial information: NCT03761017.