5 results on '"Roxana S. Dronca"'
Search Results
2. Temporal and spatial discordance of programmed cell death-ligand 1 expression and lymphocyte tumor infiltration between paired primary lesions and brain metastases in lung cancer
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Aaron S. Mansfield, Susan M. Harrington, Haidong Dong, Marie Christine Aubry, Sean S. Park, Justin C. Moser, and Roxana S. Dronca
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PD-L1 ,Adult ,Male ,0301 basic medicine ,Pathology ,medicine.medical_specialty ,Lung Neoplasms ,CD3 Complex ,Lymphocyte ,CD3 ,Clinical Decision-Making ,Programmed Cell Death 1 Receptor ,B7-H1 Antigen ,Onco-Immunology ,03 medical and health sciences ,Lymphocytes, Tumor-Infiltrating ,0302 clinical medicine ,Biomarkers, Tumor ,Tumor Microenvironment ,medicine ,metastasis ,Humans ,tumor immunology ,Lung cancer ,Aged ,Tumor microenvironment ,Lung ,biology ,Brain Neoplasms ,business.industry ,Original Articles ,Hematology ,Middle Aged ,medicine.disease ,Gene Expression Regulation, Neoplastic ,lung cancer ,Exact test ,030104 developmental biology ,medicine.anatomical_structure ,Oncology ,030220 oncology & carcinogenesis ,biology.protein ,Immunohistochemistry ,Female ,heterogeneity ,business ,Infiltration (medical) - Abstract
The tumor microenvironments of paired primary lung cancers and brain metastases are significantly different, such that many of the metastases lose PD-L1 expression, lymphocyte infiltration or both with greater discrepancies over time. The spatial and temporal heterogeneity of PD-L1 expression may limit its use as a tissue-based predictive biomarker in lung cancer., Background The dynamics of PD-L1 expression may limit its use as a tissue-based predictive biomarker. We sought to expand our understanding of the dynamics of PD-L1 expression and tumor-infiltrating lymphocytes (TILs) in patients with lung cancer-related brain metastases. Experimental design Paired primary lung cancers and brain metastases were identified and assessed for PD-L1 and CD3 expression by immunohistochemistry. Lesions with 5% or greater PD-L1 expression were considered positive. Agreement statistics and the χ2 or Fisher's exact test were used for analysis. Results We analyzed 146 paired lesions from 73 cases. There was disagreement of tumor cell PD-L1 expression in 10 cases (14%, κ = 0.71), and disagreement of TIL PD-L1 expression in 19 cases (26%, κ = 0.38). Most paired lesions with discordant tumor cell expression of PD-L1 were obtained 6 or more months apart. When specimens were categorized using a proposed tumor microenvironment categorization scheme based on PD-L1 expression and TILs, there were significant changes in the classifications because many of the brain metastases lacked either PD-L1 expression, tumor lymphocyte infiltration or both even when they were present in the primary lung cancer specimens (P = 0.009). Conclusions We identified that there are significant differences between the tumor microenvironment of paired primary lung cancers and brain metastases. When physicians decide to treat patients with lung cancer with a PD-1 or PD-L1 inhibitor, they must do so in the context of the spatial and temporal heterogeneity of the tumor microenvironment.
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- 2016
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3. 1026MO Phase Ib dose escalation study of novel immunogenic cell death (ICD) inducer PT-112 plus PD-L1 inhibitor avelumab in solid tumours
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Roxana S. Dronca, T.D. Ames, Aaron S. Mansfield, R. Camidge, Jose Jimeno, Brian A. Costello, Daniel D. Karp, and Alan H. Bryce
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Avelumab ,Oncology ,business.industry ,Phase (matter) ,Cancer research ,Dose escalation ,Immunogenic cell death ,Medicine ,Inducer ,Hematology ,PD-L1 inhibitor ,business ,medicine.drug - Published
- 2020
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4. Immune-related adverse events: Comparison of melanoma and non-small cell lung cancer patients treated with anti-PD1 therapy
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Y. Lou, Richard W. Joseph, Roxana S. Dronca, Konstantinos Leventakos, Clay T Reed, Rami Manochakian, Thorvardur R. Halfdanarson, Katherine P. Hoversten, Narjust Duma, Abdel Ghani Azzouqa, Andrea N. Sitek, Julian R. Molina, and Siddhartha Yadav
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0301 basic medicine ,Oncology ,medicine.medical_specialty ,business.industry ,Melanoma ,Hematology ,medicine.disease ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Immune system ,030220 oncology & carcinogenesis ,Internal medicine ,medicine ,Non small cell ,Adverse effect ,Lung cancer ,Anti pd1 ,business - Published
- 2018
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5. Pembrolizumab (Pembro; Mk-3475) for Advanced Melanoma (Mel): Randomized Comparison of Two Dosing Schedules
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Soonmo Peter Kang, Hassane M. Zarour, F.S. Hodi, Jill A. Lindia, Scot Ebbinghaus, Amita Patnaik, W. Hwu, Tara C. Gangadhar, Caroline Robert, Omid Hamid, Anthony M. Joshua, Adil Daud, Antoni Ribas, Y. Ge, Jedd D. Wolchok, Richard F. Kefford, Peter Hersey, Jeffrey S. Weber, Maxine Giannotti, and Roxana S. Dronca
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Antitumor activity ,medicine.medical_specialty ,Study drug ,business.industry ,Hematology ,Pembrolizumab ,Clinical trial ,Safety profile ,Oncology ,Dosing schedules ,Internal medicine ,medicine ,business ,Objective response ,Advanced melanoma - Abstract
Aim: Pembro has demonstrated strong antitumor activity in patients (pts) with advanced MEL at doses of 10 mg/kg every 2 weeks (Q2W), 10 mg/kg Q3W, and 2 mg/kg Q3W. Previous randomized data from KEYNOTE-001 showed no difference in efficacy or safety between 10 mg/kg Q3W and 2 mg/kg Q3W. Methods: To formally compare the efficacy and safety of pembro dosing schedules of 10 mg/kg Q3W and 10 mg/kg Q2W, an additional 244 pts were enrolled in KEYNOTE-001 and randomized 1:1 to treatment with pembro 10 mg/kg Q3W (n = 121) or 10 mg/kg Q2W (n = 123). Ipilimumab-naive (IPI-N) pts received ≤2 prior systemic therapies; IPI-treated (IPI-T) pts were not restricted by prior therapy. Response was assessed every 12 wk. Primary end point was objective response rate (ORR) per RECIST v1.1 by independent central review. Results: As of Feb 2014, median follow-up was approximately 35 wk, and all pts had ≥26 wk follow-up. Arms were balanced for known prognostic factors. Median treatment duration was 21 wk for the Q3W arm and 22 wk for the Q2W arm. Among the 224 pts evaluable for ORR (n = 108 at Q3W, 116 at Q2W), no significant difference was observed between schedules (28% at Q3W [n = 1 complete response, 29 partial responses] vs 33% at Q2W [n = 4 complete response, 34 partial responses]; P = .419). Across schedules, confirmed ORR was 33% in IPI-N (n = 115) and 28% in IPI-T (n = 109) pts. Disease control rate was 44% at Q3W and 50% at Q2W (P = .4064). 24-wk progression-free survival (PFS) rates were 43% at Q3W and 47% at Q2W, and there was no significant difference in PFS between schedules (HR, 1.19; 95% CI, 0.85–1.66; P = .298). The safety profile was similar for both schedules, with grade 3–4 treatment-related adverse events (AEs) observed in 12% of pts at Q3W and 15% at Q2W, discontinuations due to treatment-related AEs in 1% at Q3W and 3% at Q2W, and no treatment-related deaths. Conclusions: Overall, pembro showed similar efficacy and safety at 10 mg/kg Q2W and 10 mg/kg Q3W in pts with advanced MEL. Considering previous randomized data showing no significant difference in efficacy and safety between pembro doses of 10 mg/kg Q3W and 2 mg/kg Q3W, the recommended pembro dose and schedule is 2 mg/kg Q3W. Disclosure: C. Robert: Advisory board member for Merck, Roche, Bristol-Myers Squibb, GlaxoSmithKline, Novartis, and Amgen; J.S. Weber: Research funding and personal fees from Merck; A. Ribas: Research funding, advisory board membership, and honoraria from Merck; F.S. Hodi: Research funding from Merck and unpaid consultant to Merck; R.F. Kefford: Travel paid by Merck, Bristol-Myers Squibb, Roche, and Novartis; advisory board membership for Merck, Bristol-Myers Squibb, GlaxoSmithKline, Roche, and Novartis; honoraria from Merck; A. Daud: Research funding from and advisory board membership for Amgen, Genentech, GlaxoSmithKline, OncoSec, and Roche; J.D. Wolchok: Research funding from Merck and Bristol-Myers Squibb and advisory board membership for Merck; W-J. Hwu: Funding for research, clinical trial support, and study drug from Merck; A. Patnaik and H. Zarour: Research funding from Merck; Y. Ge, J.A. Lindia, M. Giannotti, S. Ebbinghaus and S.P. Kang: Employee of and stock ownership in Merck Sharp & Dohme, a subsidiary of Merck & Co, Inc;O. Hamid: Research funding from and consultant for Merck. All other authors have declared no conflicts of interest.
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- 2014
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