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https://www.readbyqxmd.com/read/28835114/challenges-faced-when-identifying-patients-for-combination-immunotherapy
#1
Marc S Ernstoff, Shipra Gandhi, Manu Pandey, Igor Puzanov, Petros Grivas, Alberto Montero, Vamsidhar Velcheti, Mary Jo Turk, Claudia Marcela Diaz-Montero, Lionel D Lewis, Carl Morrison
In 1996, Jim Allison demonstrated that blocking the immune regulatory molecule CTLA-4 with anit-CTLA4 antibody led to enhance tumor responses in mice. It would take an additional 15 years for human studies to confirm the potency and clinical efficacy of anti-CTLA4, ultimately leading to US FDA approval of the first checkpoint inhibitor, ipilimumab. Now with a plethora of immune-modulating agents demonstrating single agent safety and benefit across many tumor types, investigation on the optimal combination of immune-based therapies has begun in earnest...
August 2017: Future Oncology
https://www.readbyqxmd.com/read/28620848/cost-effectiveness-of-pembrolizumab-vs-standard-of-care-chemotherapy-as-first-line-treatment-for-metastatic-nsclc-that-expresses-high-levels-of-pd-l1-in-the-united-states
#2
Min Huang, Yanyan Lou, James Pellissier, Thomas Burke, Frank Xiaoqing Liu, Ruifeng Xu, Vamsidhar Velcheti
OBJECTIVES: Our objectives were to evaluate the cost effectiveness of pembrolizumab compared with standard-of-care (SoC) platinum-based chemotherapy as first-line treatment in patients with metastatic non-small-cell lung cancer (NSCLC) that expresses high levels of programmed death ligand-1 (PD-L1) [tumour proportion score (TPS) ≥50%], from a US third-party public healthcare payer perspective. METHODS: We conducted a partitioned-survival model with a cycle length of 1 week and a base-case time horizon of 20 years...
June 15, 2017: PharmacoEconomics
https://www.readbyqxmd.com/read/28561650/higher-level-pathway-objectives-of-epigenetic-therapy-a-solution-to-the-p53-problem-in-cancer
#3
Vamsidhar Velcheti, Tomas Radivoyevitch, Yogen Saunthararajah
Searches for effective yet nontoxic oncotherapies are searches for exploitable differences between cancer and normal cells. In its core of cell division, cancer resembles normal life, coordinated by the master transcription factor MYC. Outside of this core, apoptosis and differentiation programs, which dominantly antagonize MYC to terminate cell division, necessarily differ between cancer and normal cells, as apoptosis is suppressed by biallelic inactivation of the master regulator of apoptosis, p53, or its cofactor p16/CDKN2A in approximately 80% of cancers...
2017: American Society of Clinical Oncology Educational Book
https://www.readbyqxmd.com/read/28499515/incidence-of-pneumonitis-with-use-of-programmed%C3%A2-death-1-and-programmed-death-ligand-1-inhibitors%C3%A2-in%C3%A2-non-small-cell%C3%A2-lung%C3%A2-cancer-a-systematic-review-and-meta-analysis-of-trials
#4
REVIEW
Monica Khunger, Sagar Rakshit, Vinay Pasupuleti, Adrian V Hernandez, Peter Mazzone, James Stevenson, Nathan A Pennell, Vamsidhar Velcheti
BACKGROUND: Programmed death 1 (PD-1) programmed death-ligand 1 (PD-L1) inhibitors show significant clinical activity in non-small cell lung carcinoma (NSCLC). However, they are often associated with potentially fatal immune-mediated pneumonitis. Preliminary reports of trials suggest a difference in the rate of pneumonitis with PD-1 and PD-L1 inhibitors. We sought to determine the overall incidence of pneumonitis and differences according to type of inhibitors and prior chemotherapy use...
August 2017: Chest
https://www.readbyqxmd.com/read/28447912/targeting-ret-in-patients-with-ret-rearranged-lung-cancers-results-from-the-global-multicenter-ret-registry
#5
MULTICENTER STUDY
Oliver Gautschi, Julie Milia, Thomas Filleron, Juergen Wolf, David P Carbone, Dwight Owen, Ross Camidge, Vignhesh Narayanan, Robert C Doebele, Benjamin Besse, Jordi Remon-Masip, Pasi A Janne, Mark M Awad, Nir Peled, Chul-Cho Byoung, Daniel D Karp, Michael Van Den Heuvel, Heather A Wakelee, Joel W Neal, Tony S K Mok, James C H Yang, Sai-Hong Ignatius Ou, Georg Pall, Patrizia Froesch, Gérard Zalcman, David R Gandara, Jonathan W Riess, Vamsidhar Velcheti, Kristin Zeidler, Joachim Diebold, Martin Früh, Sebastian Michels, Isabelle Monnet, Sanjay Popat, Rafael Rosell, Niki Karachaliou, Sacha I Rothschild, Jin-Yuan Shih, Arne Warth, Thomas Muley, Florian Cabillic, Julien Mazières, Alexander Drilon
Purpose In addition to prospective trials for non-small-cell lung cancers (NSCLCs) that are driven by less common genomic alterations, registries provide complementary information on patient response to targeted therapies. Here, we present the results of an international registry of patients with RET-rearranged NSCLCs, providing the largest data set, to our knowledge, on outcomes of RET-directed therapy thus far. Methods A global, multicenter network of thoracic oncologists identified patients with pathologically confirmed NSCLC that harbored a RET rearrangement...
May 1, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28295386/an-integrated-segmentation-and-shape-based-classification-scheme-for-distinguishing-adenocarcinomas-from-granulomas-on-lung-ct
#6
Mehdi Alilou, Niha Beig, Mahdi Orooji, Prabhakar Rajiah, Vamsidhar Velcheti, Sagar Rakshit, Niyoti Reddy, Michael Yang, Frank Jacono, Robert C Gilkeson, Philip Linden, Anant Madabhushi
PURPOSE: Distinguishing between benign granulmoas and adenocarcinomas is confounded by their similar visual appearance on routine CT scans. Unfortunately, owing to the inability to discriminate these lesions radigraphically, many patients with benign granulomas are subjected to unnecessary surgical wedge resections and biopsies for pathologic confirmation of cancer presence or absence. This suggests the need for improved computerized characterization of these nodules in order to distinguish between these two classes of lesions on CT scans...
March 14, 2017: Medical Physics
https://www.readbyqxmd.com/read/28152686/patient-centered-outcomes-with-post-approval-nivolumab-in-metastatic-nsclc-at-the-cleveland-clinic-taussig-cancer-institute-tci
#7
Katherine Glass, Alicia M Redden, Nathan A Pennell, James Stevenson, Vamsidhar Velcheti, Emily Van Wagoner, Chad W Cummings, Brian James Bolwell
29 Background: Patient-centered outcomes are important quality metrics of value-based cancer care. For NSCLC, these include chemotherapy administration within 30 days of death and end of life hospitalizations. Nivolumab was initially FDA approved in March 2015 for second-line therapy of squamous NSCLC and subsequently for non-squamous NSCLC. To evaluate the impact of post-approval nivolumab use on patient-centered outcomes, a retrospective review was performed of patients (pts) with metastatic NSLCC receiving nivolumab at TCI main campus and regional centers...
March 2016: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28024926/durable-response-to-combination-of-dabrafenib-and-trametinib-in-braf-v600e-mutated-non-small-cell-lung-cancer
#8
Leah M Pervere, Sagar Rakshit, Alexa B Schrock, Vincent A Miller, Siraj M Ali, Vamsidhar Velcheti
No abstract text is available yet for this article.
November 11, 2016: Clinical Lung Cancer
https://www.readbyqxmd.com/read/27969521/ps01-54-evaluation-of-novel-blood-based-biomarkers-with-atezolizumab-monotherapy-in-1l-advanced-or-metastatic-nsclc-b-f1rst-topic-medical-oncology
#9
Mark A Socinski, Joan Schiller, Shaker Dakhil, Shayma Kazmi, Joseph Leach, Sylvia Hu, Sarah M Paul, David S Shames, See Phan, Cindy Yun, Vamsidhar Velcheti
No abstract text is available yet for this article.
November 2016: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/27903463/her2-transmembrane-domain-tmd-mutations-v659-g660-that-stabilize-homo-and-heterodimerization-are-rare-oncogenic-drivers-in-lung-adenocarcinoma-that-respond-to-afatinib
#10
Sai-Hong Ignatius Ou, Alexa B Schrock, Eduard V Bocharov, Samuel J Klempner, Carolina Kawamura Haddad, Gary Steinecker, Melissa Johnson, Barbara J Gitlitz, Jon Chung, Paulo V Campregher, Jeffrey S Ross, Philip J Stephens, Vincent A Miller, James H Suh, Siraj M Ali, Vamsidhar Velcheti
INTRODUCTION: Erb-b2 receptor tyrosine kinase (HER2) transmembrane domain (TMD) mutations (HER2(V659E), HER2(G660D)) have previously been identified in lung adenocarcinomas, but their frequency and clinical significance is unknown. METHODS: We prospectively analyzed 8551 consecutive lung adenocarcinomas using hybrid capture-based comprehensive genomic profiling (CGP) at the request of the individual treating physicians for the purpose of making therapy decisions...
March 2017: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/27831813/breast-mass-in-a-woman-with-recurrent-thymoma
#11
Charles D Sturgis, Dana Ataya, Benjamin C Calhoun, Vamsidhar Velcheti, Sanjay Mukhopadhyay
No abstract text is available yet for this article.
November 2016: Annals of the American Thoracic Society
https://www.readbyqxmd.com/read/27668174/focal-lung-infiltrate-complicating-pd-1-inhibitor-use-a-new-pattern-of-drug-associated-lung-toxicity
#12
Sameep Sehgal, Vamsidhar Velcheti, Sanjay Mukhopadhyay, James K Stoller
A 58-year-old woman with stage 4 adenocarcinoma of the lung being treated with pembrolizumab developed dyspnea, non-productive cough, and a right middle lobe infiltrate. Complete resolution of the infiltrate with cessation of pembrolizumab, initiation of prednisone and no antibiotic therapy suggested drug-associated lung toxicity as the cause. While the programmed death-1 (PD-1) inhibitors -pembrolizumab and nivolumab - have been implicated as a cause of diffuse or multifocal pulmonary infiltrates, the current case represents, to our knowledge, the first instance of a unilobar, focal infiltrate associated with their use...
2016: Respiratory Medicine Case Reports
https://www.readbyqxmd.com/read/27571538/cost-effectiveness-of-pembrolizumab-versus-docetaxel-for-the-treatment-of-previously-treated-pd-l1-positive-advanced-nsclc-patients-in-the-united-states
#13
COMPARATIVE STUDY
Min Huang, Yanyan Lou, James Pellissier, Thomas Burke, Frank Xiaoqing Liu, Ruifeng Xu, Vamsidhar Velcheti
OBJECTIVES: This analysis aimed to evaluate the cost-effectiveness of pembrolizumab compared with docetaxel in patients with previously treated advanced non-squamous cell lung cancer (NSCLC) with PD-L1 positive tumors (total proportion score [TPS] ≥ 50%). The analysis was conducted from a US third-party payer perspective. METHODS: A partitioned-survival model was developed using data from patients from the KEYNOTE 010 clinical trial. The model used Kaplan-Meier (KM) estimates of progression-free survival (PFS) and overall survival (OS) from the trial for patients treated with either pembrolizumab 2 mg/kg or docetaxel 75 mg/m(2) with extrapolation based on fitted parametric functions and long-term registry data...
February 2017: Journal of Medical Economics
https://www.readbyqxmd.com/read/27566797/checkpoint-immunotherapy-good-for-cancer-therapy-bad-for-rheumatic-diseases
#14
EDITORIAL
Leonard Calabrese, Vamsidhar Velcheti
No abstract text is available yet for this article.
January 2017: Annals of the Rheumatic Diseases
https://www.readbyqxmd.com/read/27440266/differential-expression-and-significance-of-pd-l1-ido-1-and-b7-h4-in-human-lung-cancer
#15
Kurt A Schalper, Daniel Carvajal-Hausdorf, Joseph McLaughlin, Mehmet Altan, Vamsidhar Velcheti, Patricia Gaule, Miguel F Sanmamed, Lieping Chen, Roy S Herbst, David L Rimm
PURPOSE: To determine the expression level, associations, and biological role of PD-L1, IDO-1, and B7-H4 in non-small cell lung cancer (NSCLC). EXPERIMENTAL DESIGN: Using multiplexed quantitative immunofluorescence (QIF), we measured the levels of PD-L1, IDO-1, B7-H4, and different tumor-infiltrating lymphoycte (TIL) subsets in 552 stages I-IV lung carcinomas from two independent populations. Associations between the marker levels, TILs, and major clinicopathologic variables were determined...
January 15, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27249709/basic-overview-of-current-immunotherapy-approaches-in-cancer
#16
REVIEW
Vamsidhar Velcheti, Kurt Schalper
Recent success of immunotherapy strategies such as immune checkpoint blockade in several malignancies has established the role of immunotherapy in the treatment of cancer. Cancers use multiple mechanisms to co-opt the host-tumor immune interactions, leading to immune evasion. Our understanding of the host-tumor interactions has evolved over the past few years and led to various promising new therapeutic strategies. This article will focus on the basic principles of immunotherapy, novel pathways/agents, and combinatorial immunotherapies...
2016: American Society of Clinical Oncology Educational Book
https://www.readbyqxmd.com/read/26759474/reduction-of-inappropriate-prophylactic-pegylated-granulocyte-colony-stimulating-factor-use-for-patients-with-non-small-cell-lung-cancer-who-receive-chemotherapy-an-asco-quality-training-program-project-of-the-cleveland-clinic-taussig-cancer-institute
#17
Lindsey Martin Goodman, Machelle B Moeller, Abdel-Ghani Azzouqa, Amy E Guthrie, Carole K Dalby, Marc A Earl, Connie Cheng, Nathan A Pennell, Marc Shapiro, Vamsidhar Velcheti, James P Stevenson
PURPOSE: Routine prophylactic pegylated granulocyte colony-stimulating factor (pGCSF) administration for patients receiving chemotherapy regimens associated with low risk (< 10%) for neutropenic fever (LRNF) is not recommended. Inappropriate use of pGCSF increases patient morbidity and health care costs. METHODS: A multidisciplinary team reviewed the charts of patients with non-small-cell lung cancer (NSCLC) at the Taussig Cancer Institute in whom a new chemotherapy regimen was initiated from April through November 2013...
January 2016: Journal of Oncology Practice
https://www.readbyqxmd.com/read/26585927/quantification-of-anaplastic-lymphoma-kinase-protein-expression-in-non-small-cell-lung-cancer-tissues-from-patients-treated-with-crizotinib
#18
Todd Hembrough, Wei-Li Liao, Christopher P Hartley, Patrick C Ma, Vamsidhar Velcheti, Christopher Lanigan, Sheeno Thyparambil, Eunkyung An, Manish Monga, David Krizman, Jon Burrows, Laura J Tafe
BACKGROUND: Crizotinib has antitumor activity in ALK (anaplastic lymphoma receptor tyrosine kinase)-rearranged non-small cell lung cancer (NSCLC). The current diagnostic test for ALK rearrangement is breakapart fluorescence in situ hybridization (FISH), but FISH has low throughput and is not always reflective of protein concentrations. The emergence of multiple clinically relevant biomarkers in NSCLC necessitates efficient testing of scarce tissue samples. We developed an anaplastic lymphoma kinase (ALK) protein assay that uses multiplexed selected reaction monitoring (SRM) to quantify absolute amounts of ALK in formalin-fixed paraffin-embedded (FFPE) tumor tissue...
January 2016: Clinical Chemistry
https://www.readbyqxmd.com/read/26562159/quantitative-assessment-of-the-heterogeneity-of-pd-l1-expression-in-non-small-cell-lung-cancer
#19
COMPARATIVE STUDY
Joseph McLaughlin, Gang Han, Kurt A Schalper, Daniel Carvajal-Hausdorf, Vasiliki Pelekanou, Jamaal Rehman, Vamsidhar Velcheti, Roy Herbst, Patricia LoRusso, David L Rimm
IMPORTANCE: Early-phase trials with monoclonal antibodies targeting PD-1 (programmed cell death protein 1) and PD-L1 (programmed cell death 1 ligand 1) have demonstrated durable clinical responses in patients with non-small-cell lung cancer (NSCLC). However, current assays for the prognostic and/or predictive role of tumor PD-L1 expression are not standardized with respect to either quantity or distribution of expression. OBJECTIVE: To demonstrate PD-L1 protein distribution in NSCLC tumors using both conventional immunohistochemistry (IHC) and quantitative immunofluorescence (QIF) and compare results obtained using 2 different PD-L1 antibodies...
January 2016: JAMA Oncology
https://www.readbyqxmd.com/read/26408403/evaluation-of-pd-l1-expression-and-associated-tumor-infiltrating-lymphocytes-in-laryngeal-squamous-cell-carcinoma
#20
Maria Vassilakopoulou, Margaritis Avgeris, Vamsidhar Velcheti, Vassiliki Kotoula, Theodore Rampias, Kyriakos Chatzopoulos, Christos Perisanidis, Christos K Kontos, Aris I Giotakis, Andreas Scorilas, David Rimm, Clarence Sasaki, George Fountzilas, Amanda Psyrri
PURPOSE: Programmed death-ligand 1 (PD-L1; also known as CD274 or B7-H1) expression represents a mechanism of immune escape for cancer. Our purpose was to characterize tumor PD-L1 expression and associated T-cell infiltration in primary laryngeal squamous cell carcinomas (SCC). EXPERIMENTAL DESIGN: A well-annotated cohort of 260 operable primary laryngeal SCCs [formalin-fixed paraffin-embedded (FFPE) specimens] was morphologically characterized for stromal tumor-infiltrating lymphocytes (TIL), on hematoxylin/eosin-stained whole sections and for PD-L1 mRNA expression by qRT-PCR in FFPE specimens...
February 1, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
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