tbuckley/cabot-search huggingface dataset:
AdvanTIG-302: Anti-TIGIT monoclonal antibody (mAb) ociperlimab (OCI) plus tislelizumab (TIS) versus pembrolizumab (PEM) in programmed death ligand-1 (PD-L1) selected, previously untreated, locally advanced, unresectable or metastatic non-small cell lung cancer (NSCLC).
Authors: Mark A. Socinski, Alexander I. Spira, Luis G. Paz-Ares, Martin Reck, Shun Lu, Makoto Nishio, Jiang Li, Yunfei Zhou, Joon Whan Rhee, Sandra Chica Duque, Xinmin Yu
Journal: Journal of Clinical Oncology (2021)

TPS9128 Background: Monotherapy with programmed death 1 (PD-1)/PD-L1 antibodies has improved clinical outcomes for patients (pts) with non-oncogenic driven NSCLC but clinical responses are limited by primary and secondary resistance, and improvements in durability of response are required. T-cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibition motif domain (TIGIT) is a co-inhibitory, immune checkpoint receptor upregulated on T-cells and natural killer cells in multiple solid tumors, which can inhibit anticancer immune responses. OCI (BGB-A1217) is a novel, humanized mAb that binds to TIGIT with high affinity and specificity, which has demonstrated competent binding with C1q and all Fcγ receptors while inducing antibody-dependent cellular cytotoxicity. Preclinical and clinical studies suggest that dual targeting with anti-TIGIT and anti-PD-1 antibodies produces synergistic immune cell activation and enhanced antitumor activity. Methods: AdvanTIG-302 is a Phase 3, multicenter, international, randomized, double-blind study (NCT04746924) investigating OCI in combination with TIS compared with PEM in adult pts (≥ 18 years of age) with PD-L1 selected, previously untreated, locally advanced, unresectable or metastatic NSCLC without oncogenic EGFR or ALK mutation. Approximately 605 pts will be randomized 5:5:1 to receive: OCI 900 mg intravenously (IV) plus TIS 200 mg IV every three weeks (Q3W; Arm A), PEM 200 mg IV plus placebo IV Q3W (Arm B) or TIS 200 mg IV plus placebo IV Q3W (Arm C). Pts will be treated until disease progression, loss of clinical benefit, intolerable toxicity or withdrawal of consent. Stratification factors include histology (squamous vs non-squamous) and region (Asian vs non-Asian). Cross-over is not permitted. Key eligibility criteria include histologically confirmed disease, PD-L1 expression ≥ 50%, no known EGFR or ALK mutations and no prior checkpoint inhibitor therapy. Dual primary endpoints are investigator-assessed progression-free survival (PFS; RECIST v1.1) and overall survival (Arms A and B) in the Intention-to-Treat population. Secondary endpoints include PFS (assessed by Blinded Independent Review Committee), investigator-assessed overall response rate and duration of response, safety and tolerability, and patient-reported health-related quality of life (EORTC-QLQ-C30, QLQ-LC13 and EQ-5D-5L; Arms A and B). Exploratory endpoints include disease control rate, clinical benefit rate and time to response. This study will also evaluate the association between biomarkers and response or resistance. Study enrollment has begun and recruitment is ongoing. Clinical trial information: NCT04746924.
Cost-effectiveness of adjuvant chemotherapy for stage III colon cancer in the South African public healthcare setting.
Authors: Yoanna S Pumpalova, Alexandra M. Rogers, Sarah Xinhui Tan, Candice-Lee Herbst, Paul Ruff, Alfred I. Neugut, Chin Hur
Journal: Journal of Clinical Oncology (2021)

e18849 Background: Colon cancer incidence and mortality rates are increasing in low- and middle-income countries, such as South Africa (SA). Adjuvant chemotherapy after curative resection for stage III colon cancer prolongs overall survival, but it is unclear which regimen is most cost-effective in resource-constrained settings, such as the SA public healthcare system. Methods: A decision-analytic Markov model was developed to compare lifetime costs and health outcomes for 60-year-old stage III colon cancer patients treated with six adjuvant chemotherapy regimens in a public hospital in SA: fluorouracil, leucovorin, and oxaliplatin (FOLFOX) for 3 and 6 months, capecitabine and oxaliplatin (CAPOX) for 3 and 6 months, capecitabine for 6 months, and fluorouracil/leucovorin (5-FU/LV; Mayo regimen) for 6 months. Transition probabilities were derived from clinical trials to estimate risks of toxicity, disease recurrence, and survival. Costs from a SA societal perspective and utility estimates were obtained from literature and local expert opinion. The primary outcome was the incremental cost-effectiveness ratio (ICER) in international dollars (I$) per disability-adjusted life year (DALY) averted, with a willingness-to-pay (WTP) threshold of one times the 2020 GDP per capita of SA (I$13,006.57; ZAR89,225). Results: Our model found CAPOX for 3 months to be the most cost-effective strategy, at a lifetime cost below the local WTP threshold (I$5,380.82; ZAR36,912.44) and 5.74 DALYs averted, compared to no chemotherapy. FOLFOX for 6 months was also on the efficiency frontier, with a higher total cost (I$22,747.47; ZAR156,047.64) and 0.18 additional DALYs averted (ICER = I$99,021.35/DALY averted). All other strategies were absolutely dominated. One-way sensitivity analyses found that FOLFOX for 6 months is optimal when the administration cost (i.e.: port and pump) falls to 20% of the base case price. Conclusions: In the SA public healthcare system, CAPOX for 3 months is the most cost-effective adjuvant treatment for stage III colon cancer. FOLFOX for 6 months, with a greater effectiveness, may be cost-effective if the administration cost decreases significantly. The optimal strategy in other settings may vary according to the local WTP threshold.[Table: see text]
Effectiveness of Blood Lipid Management in Patients With Peripheral Artery Disease
Authors: Connie N. Hess, Christopher P. Cannon, Joshua A. Beckman, Philip P. Goodney, Manesh R. Patel, William R. Hiatt, Katherine E. Mues, Kate K. Orroth, Erin Shannon, Marc P. Bonaca
Journal: Journal of the American College of Cardiology (2021)
Peer-to-Peer Support for Older Adults—What Do We Know and Where Do We Go?
Authors: Brett D. Thombs, Andrea Carboni-Jiménez
Journal: JAMA Network Open (2021)

Rebecca J. Schwei, MPH; Scott Hetzel, MS; KyungMann Kim, PhD; Jane Mahoney, MD; Kali DeYoung, BA; Jenni Frumer, PhD, LCSW, MSEd; Ross P. Lanzafame, JD; Jenny Madlof, BA; Alis Simpson, EdD; Erika Zambrano-Morales, MA; Elizabeth A. Jacobs, MD, MAPP
Is it anemia an independent prognostic factor of patients with renal cell carcinoma? A university hospital experience.
Authors: Bruna Bighetti, Giuliana Seo, Pamela Reinaldo Leite, Thais Jesus, Gyovanna Luz, Ilka Lopes Santoro, Hakaru Tadokoro, Tiago Padua
Journal: Journal of Clinical Oncology (2021)

e16501 Background: Clear cell carcinoma (RCC) is the most common histologic type of renal cancer. It is well established that, for this specific histology, six main prognostic factors interact into a score and can categorize it into three different prognostic groups: favorable-risk, intermediate-risk, and poor-risk. These six factors are anemia, thrombocytosis, neutrophilia, hypercalcemia, Karnofsky performance status &lt; 80%, and &lt; 1 year from diagnosis to treatment. The objective of this study is to evaluate if any of these prognostic factors can independently predict a worse prognosis. Methods: We conducted a retrospective study with 51 patients treated in our national reference institution. The great majority of them were RCC. We analyzed the overall survival (OS) of each one of the six classic risk factors adding to that the body mass index (BMI), the presence of metastasis at diagnosis time, and comorbidities. Results: The analysis of most of the indexed parameters did not show a statistical difference, but anemia and the presence of metastasis at the time of diagnosis. We found that the anemia itself denotes a Hazard Ratio (HR) of 2,35 (p = 0,034). Moreover, if it is adjusted for age and sex, the HR reduces at 1,149, sustaining its statistical significance yet. The presence of metastasis at the time of diagnosis is translated as an HR = 2,029 (p = 0,049), bringing into light something already known in clinical practice, but still, a lower risk compared to anemia. Conclusions: The six classic risk factors for RRC survival pooled together can interact and predict the OS and patient’s prognosis. Our study suggests that the anemia itself can predict independently a worst-case scenario, which emphasizes the importance of this analysis upfront. A larger prospective cohort is warranted to further understanding this framework.
Treatment of Multisystem Inflammatory Syndrome in Children
Authors: Andrew J. McArdle, Ortensia Vito, Harsita Patel, Eleanor G. Seaby, Priyen Shah, Clare Wilson, Claire Broderick, Ruud Nijman, Adriana H. Tremoulet, Daniel Munblit, Rolando Ulloa-Gutierrez, Michael J. Carter, Tisham De, Clive Hoggart, Elizabeth Whittaker, Jethro A. Herberg, Myrsini Kaforou, Aubrey J. Cunnington, Michael Levin
Journal: New England Journal of Medicine (2021)

Evidence is urgently needed to support treatment decisions for children with multisystem inflammatory syndrome (MIS-C) associated with severe acute respiratory syndrome coronavirus 2.We performed an international observational cohort study of clinical and outcome data regarding suspected MIS-C that had been uploaded by physicians onto a Web-based database. We used inverse-probability weighting and generalized linear models to evaluate intravenous immune globulin (IVIG) as a reference, as compared with IVIG plus glucocorticoids and glucocorticoids alone. There were two primary outcomes: the first was a composite of inotropic support or mechanical ventilation by day 2 or later or death; the second was a reduction in disease severity on an ordinal scale by day 2. Secondary outcomes included treatment escalation and the time until a reduction in organ failure and inflammation.Data were available regarding the course of treatment for 614 children from 32 countries from June 2020 through February 2021; 490 met the World Health Organization criteria for MIS-C. Of the 614 children with suspected MIS-C, 246 received primary treatment with IVIG alone, 208 with IVIG plus glucocorticoids, and 99 with glucocorticoids alone; 22 children received other treatment combinations, including biologic agents, and 39 received no immunomodulatory therapy. Receipt of inotropic or ventilatory support or death occurred in 56 patients who received IVIG plus glucocorticoids (adjusted odds ratio for the comparison with IVIG alone, 0.77; 95% confidence interval [CI], 0.33 to 1.82) and in 17 patients who received glucocorticoids alone (adjusted odds ratio, 0.54; 95% CI, 0.22 to 1.33). The adjusted odds ratios for a reduction in disease severity were similar in the two groups, as compared with IVIG alone (0.90 for IVIG plus glucocorticoids and 0.93 for glucocorticoids alone). The time until a reduction in disease severity was similar in the three groups.We found no evidence that recovery from MIS-C differed after primary treatment with IVIG alone, IVIG plus glucocorticoids, or glucocorticoids alone, although significant differences may emerge as more data accrue. (Funded by the European Union's Horizon 2020 Program and others; BATS ISRCTN number, ISRCTN69546370.).
Health-related quality of life (HRQoL) in advanced endometrial cancer (aEC) patients (pts) treated with lenvatinib plus pembrolizumab or treatment of physician’s choice (TPC).
Authors: Domenica Lorusso, Nicoletta Colombo, Antonio Casado Herraez, Alessandro Santin, Emeline Colomba, David Scott Miller, Keiichi Fujiwara, Sandro Pignata, Sally E. Baron-Hay, Isabelle Laure Ray-Coquard, Ronnie Shapira-Frommer, Yong Man Kim, Mary McCormack, Steven Bird, Vimalanand S. Prabhu, Allison Martin Nguyen, Qi Zhao, Lea Dutta, Vicky Makker
Journal: Journal of Clinical Oncology (2021)

5570 Background: In Study 309/KEYNOTE-775, lenvatinib + pembrolizumab (L+P) demonstrated significant and clinically meaningful improvement in OS, PFS, and ORR compared with TPC in aEC pts following prior platinum-based systemic therapy. Given the medical complexity/age of EC pts, QoL analyses are critical, but often under-reported. We present results of pt-reported HRQoL for Study 309/KEYNOTE-775. Methods: Pts were randomized 1:1 to receive lenvatinib 20 mg QD PO + pembrolizumab 200 mg IV Q3W (n=411) or TPC (n=416; doxorubicin 60 mg/m 2 IV Q3W or paclitaxel 80 mg/m 2 IV QW, 3 wks on/1 wk off). Pt-reported HRQoL was assessed at cycle 1 day 1, day 1 of each subsequent cycle and at time of discontinuation using EORTC QLQ-C30, its EC module QLQ-EN24, and EQ-5D-5L in treated pts who had ≥1 HRQoL assessment available. Higher scores indicate better functioning/QoL (EORTC QLQ-C30, EQ-5D-5L) or worse symptom severity (QLQ-EN24). Changes in EORTC QLQ-C30 global health status (GHS)/QoL was a secondary endpoint. This was analyzed from baseline to the latest timepoint at which overall completion was ≥60% and overall compliance was ≥80%, using constrained longitudinal data analysis; other HRQoL analyses were exploratory. Results: Completion and compliance rates of EORTC QLQ-C30 were &gt;95% in both groups at baseline. Primary analysis was conducted at wk 12 as completion rate was 80% for L+P and 62% for TPC; compliance rate was 93% for L+P and 87% for TPC. Baseline GHS/QoL scores were similar between the L+P group and TPC group: mean (SD) of 65.74 (21.87) vs 65.69 (22.71), respectively. Over 12 wks of follow-up, pts in both groups had slight decreases in GHS/QoL. Similar decreases were observed for pts receiving L+P vs TPC: -5.97 (95% CI: -8.36, -3.58) vs -6.98 (95% CI: -9.63, -4.33). The between-group difference in least-squares (LS) mean score change from baseline to wk 12 for L+P vs TPC was 1.01 points (95% CI: -2.28, 4.31). Over time, QoL scores were generally similar across treatments. Results were similar for other HRQoL endpoints (Table). Conclusions: No significant differences were observed in HRQoL scores between treatment groups. With no standard treatment approach following failure of platinum-based therapy, these data along with previously reported efficacy and safety findings from Study 309/KEYNOTE-775 further support that L+P has an overall favorable benefit/risk profile compared to chemotherapy. Clinical trial information: NCT03517449. [Table: see text]
A Phase Ib Study to Assess the Safety and Tolerability of Ruxolitinib in Combination with Azacitidine in Patients with Advanced Phase Myeloproliferative Neoplasms (MPN), Including Myelodysplastic Syndromes (MDS) or Acute Myeloid Leukaemia (AML) Arising from MPN (The Bloodwise / TAP PHAZAR Study on Behalf of the UK MPN CSG)
Authors: Mark W Drummond, Claire N. Harrison, Samuel Munoz Vicente, Adam J Mead, Christina Yap, Frederick Chen, Srinivasan Narayanan, Dragana Milojkovic, Leyre Navarro-Nunez, Steven Knapper
Journal: Blood (2017)
Hypersensitivity reactions to chemotherapy: an EAACI Position Paper
Authors: Mauro Pagani, Sevim Bavbek, Emilio Alvarez‐Cuesta, Adile Berna Dursun, Patrizia Bonadonna, Mariana Castells, Josefina Cernadas, Anca Chiriac, Hamadi Sahar, Ricardo Madrigal‐Burgaleta, Soledad Sanchez Sanchez
Journal: Allergy (2021)

Chemotherapeutic drugs have been widely used in the treatment of cancer disease for about 70 years. The development of new treatments has not hindered their use, and oncologists still prescribe them routinely, alone or in combination with other antineoplastic agents. However, all chemotherapeutic agents can induce hypersensitivity reactions (HSRs), with different incidences depending on the culprit drug. These reactions are the third leading cause of fatal drug-induced anaphylaxis in the United States. In Europe, deaths related to chemotherapy have also been reported. In particular, most reactions are caused by platinum compounds, taxanes, epipodophyllotoxins and asparaginase. Despite their prevalence and relevance, the ideal pathways for diagnosis, treatment and prevention of these reactions are still unclear, and practice remains considerably heterogeneous with vast differences from center to center. Thus, the European Network on Drug Allergy and Drug Allergy Interest Group of the European Academy of Allergy and Clinical Immunology organized a task force to provide data and recommendations regarding the allergological work-up in this field of drug hypersensitivity reactions. This position paper aims to provide consensus on the investigation of HSRs to chemotherapeutic drugs and give practical recommendations for clinicians that treat these patients, such as oncologists, allergologists and internists. Key sections cover risk factors, pathogenesis, symptoms, the role of skin tests, in vitro tests, indications and contraindications of drug provocation tests and desensitization of neoplastic patients with allergic reactions to chemotherapeutic drugs. Statements, recommendations and unmet needs were discussed and proposed at the end of each section.
Targeting the αv integrin/TGF-β axis improves natural killer cell function against glioblastoma stem cells
Authors: Hila Shaim, Mayra Shanley, Rafet Basar, May Daher, Joy Gumin, Daniel B. Zamler, Nadima Uprety, Fang Wang, Yuefan Huang, Konrad Gabrusiewicz, Qi Miao, Jinzhuang Dou, Abdullah Alsuliman, Lucila N. Kerbauy, Sunil Acharya, Vakul Mohanty, Mayela Mendt, Sufang Li, JunJun Lu, Jun Wei, Natalie W. Fowlkes, Elif Gokdemir, Emily L. Ensley, Mecit Kaplan, Cynthia Kassab, Li Li, Gonca Ozcan, Pinaki P. Banerjee, Yifei Shen, April L. Gilbert, Corry M. Jones, Mustafa Bdiwi, Ana K. Nunez-Cortes, Enli Liu, Jun Yu, Nobuhiko Imahashi, Luis Muniz-Feliciano, Ye Li, Jian Hu, Giulio Draetta, David Marin, Dihua Yu, Stephan Mielke, Matthias Eyrich, Richard E. Champlin, Ken Chen, Frederick F. Lang, Elizabeth J. Shpall, Amy B. Heimberger, Katayoun Rezvani
Journal: Journal of Clinical Investigation (2021)

Glioblastoma multiforme (GBM), the most aggressive brain cancer, recurs because glioblastoma stem cells (GSCs) are resistant to all standard therapies. We showed that GSCs, but not normal astrocytes, are sensitive to lysis by healthy allogeneic natural killer (NK) cells in vitro. Mass cytometry and single-cell RNA sequencing of primary tumor samples revealed that GBM tumor-infiltrating NK cells acquired an altered phenotype associated with impaired lytic function relative to matched peripheral blood NK cells from patients with GBM or healthy donors. We attributed this immune evasion tactic to direct cell-to-cell contact between GSCs and NK cells via αv integrin-mediated TGF-β activation. Treatment of GSC-engrafted mice with allogeneic NK cells in combination with inhibitors of integrin or TGF-β signaling or with TGFBR2 gene-edited allogeneic NK cells prevented GSC-induced NK cell dysfunction and tumor growth. These findings reveal an important mechanism of NK cell immune evasion by GSCs and suggest the αv integrin/TGF-β axis as a potentially useful therapeutic target in GBM.
Assessment of BRAF class I/II/III mutations, demographics, and treatment outcomes in NSCLC.
Authors: Julian Andres Marin-Acevedo, James Kevin Hicks, Ram Thapa, Dung-Tsa Chen, ErinMarie Kimbrough, Jhanelle Elaine Gray
Journal: Journal of Clinical Oncology (2021)

e21016 Background: BRAF mutations are grouped (class I, II or III) according to kinase activity, dependence on RAS, and dimerization. BRAF class I mutations are targeted with BRAF/MEK inhibitors. The management of class II/III mutations has not been fully elucidated. We aimed to further characterize BRAF-mutant NSCLC. Methods: Moffitt patients with BRAF-mutant NSCLC were identified through retrospective review of a clinical molecular database and electronic health record from 1/1/2012 - 03/31/2020. Demographics, PD-L1 expression, responses to chemotherapy/immunotherapy, and overall survival were collected. The correlation between BRAF mutation classes and these variables was determined using a pairwise comparison of p-values and corrected for testing using the Benjamini-Hochberg method. For survival analysis, we used the Kaplan-Meier method with log-rank test. Results: 153 patients were included. Table summarizes the demographic data. 14 evaluable patients with class I mutations received anti-BRAF therapy. The DCR was 79% (11/14) and 83% when PD-L1 ≥1% (5/6). 36 response-evaluable patients received immunotherapy. The DCR was 79% (11/14) for patients with class I, 69% (9/13) for class II, and 78% (7/9) for class III mutations (p=0.89). The DCR was 73% in those with PD-L1 ≥1% (22/30) and 44% in those with PD-L1 &lt;1% (7/16; p= 0.02). 43 response-evaluable patients received chemotherapy. The DCR was 86% (18/21) for patients with class I, 69% (9/13) for class II, and 78% (7/9) for class III mutations (p=0.49). The mOS was 26.2 months for all patients. The mOS was 31.2 months for class I, 15.6 months for class II, 28.8 months for class III, 34.8 months for AMP, and 24 months for VUS (p=0.6). Conclusions: To our knowledge, this is the largest retrospective study of patients with BRAF-mutant NSCLC. BRAFmutations were more common in patients with adenocarcinoma and those with a smoking history. PD-L1 levels ≥1% were seen more frequently in all BRAF-mutant patients. Class I mutations were significantly more common than other mutations and responded well to BRAF-targeted therapy, particularly when PD-L1 ≥1%. All BRAF-mutant classes responded similarly to immunotherapy and better responses were seen among those with PD-L1 ≥1%. Responses to chemotherapy were similar across all classes. Improved OS in class I-mutant disease was seen. These findings were not statistically significant. Additional research is needed to better characterize these patients to individualize management and improve outcomes.[Table: see text]
Plasma-derived exosomal miR-15a-5p as a promising diagnostic biomarker for early detection of endometrial carcinoma
Authors: Lanyun Zhou, Wei Wang, Fenfen Wang, Siqi Yang, Jiaqi Hu, Bingjian Lu, Zimin Pan, Yu Ma, Mengyue Zheng, Liyuan Zhou, Shufeng Lei, Penghong Song, Pengyuan Liu, Weiguo Lu, Yan Lu
Journal: Molecular Cancer (2021)

Abstract Endometrial cancer (EC) is a major cause of death among gynecologic malignancies. To improve early detection of EC in patients, we carried out a large plasma-derived exosomal microRNA (miRNA) studies for diagnostic biomarker discovery in EC. Small RNA sequencing was performed to identify candidate exosomal miRNAs as diagnostic biomarkers in 56 plasma samples from healthy subjects and EC patients. These miRNA candidates were further validated in 202 independent plasma samples by droplet digital PCR (ddPCR), 32 pairs of endometrial tumors and adjacent normal tissues by quantitative real-time PCR (qRT-PCR), and matched plasma samples of 12 patients before and after surgery by ddPCR. miR-15a-5p, miR-106b-5p, and miR107 were significantly upregulated in exomes isolated from plasma samples of EC patients compared with healthy subjects. Particularly, miR-15a-5p alone yielded an AUC value of 0.813 to distinguish EC patients with stage I from healthy subjects. The integration of miR-15a-5p and serum tumor markers (CEA and CA125) achieved a higher AUC value of 0.899. There was also a close connection between miR-15a-5p and clinical manifestations in EC patients. Its exosomal expression was not only associated with the depth of muscular infiltration and aggressiveness of EC, but also correlated with levels of reproductive hormones such as TTE and DHEAS. Collectively, plasma-derived exosomal miR-15a-5p is a promising and effective diagnostic biomarker for the early detection of endometrial cancer.