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Melanoma: HELP
Articles by Julie R. Brahmer
Based on 8 articles published since 2008
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Between 2008 and 2019, Julie Brahmer wrote the following 8 articles about Melanoma.
 
+ Citations + Abstracts
1 Review Breathing new life into immunotherapy: review of melanoma, lung and kidney cancer. 2014

Drake, Charles G / Lipson, Evan J / Brahmer, Julie R. ·Department of Oncology, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, The Bunting Blaustein Cancer Research Building, 1650 Orleans Street, Baltimore, MD 21231, USA. ·Nat Rev Clin Oncol · Pubmed #24247168.

ABSTRACT: Previously, clinical approaches to using the immune system against cancer focused on vaccines that intended to specifically initiate or amplify a host response against evolving tumours. Although vaccine approaches have had some clinical success, most cancer vaccines fail to induce objective tumour shrinkage in patients. More-recent approaches have centred on a series of molecules known as immune checkpoints-whose natural function is to restrain or dampen a potentially over-exuberant response. Blocking immune checkpoint molecules with monoclonal antibodies has emerged as a viable clinical strategy that mediates tumour shrinkage in several cancer types. In addition to being part of the current treatment armamentarium for metastatic melanoma, immune checkpoint blockade is currently undergoing phase III testing in several cancer types.

2 Clinical Trial Survival, durable tumor remission, and long-term safety in patients with advanced melanoma receiving nivolumab. 2014

Topalian, Suzanne L / Sznol, Mario / McDermott, David F / Kluger, Harriet M / Carvajal, Richard D / Sharfman, William H / Brahmer, Julie R / Lawrence, Donald P / Atkins, Michael B / Powderly, John D / Leming, Philip D / Lipson, Evan J / Puzanov, Igor / Smith, David C / Taube, Janis M / Wigginton, Jon M / Kollia, Georgia D / Gupta, Ashok / Pardoll, Drew M / Sosman, Jeffrey A / Hodi, F Stephen. ·Suzanne L. Topalian, William H. Sharfman, Julie R. Brahmer, Evan J. Lipson, Janis M. Taube, and Drew M. Pardoll, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD · Mario Sznol and Harriet M. Kluger, Yale University School of Medicine and Smilow Cancer Center, Yale-New Haven Hospital, New Haven, CT · David F. McDermott, Beth Israel Deaconess Medical Center · Donald P. Lawrence, Massachusetts General Hospital Cancer Center · F. Stephen Hodi, Dana-Farber Cancer Institute, Boston, MA · Richard D. Carvajal, Memorial Sloan-Kettering Cancer Center, New York, NY · Michael B. Atkins, Georgetown-Lombardi Comprehensive Cancer Center, Washington, DC · John D. Powderly, Carolina BioOncology Institute, Huntersville, NC · Philip D. Leming, The Christ Hospital Cancer Center, Cincinnati, OH · Igor Puzanov and Jeffrey A. Sosman, Vanderbilt University Medical Center, Nashville, TN · David C. Smith, University of Michigan, Ann Arbor, MI · and Jon M. Wigginton, Georgia D. Kollia, and Ashok Gupta, Bristol-Myers Squibb, Princeton, NJ. ·J Clin Oncol · Pubmed #24590637.

ABSTRACT: PURPOSE: Programmed cell death 1 (PD-1) is an inhibitory receptor expressed by activated T cells that downmodulates effector functions and limits the generation of immune memory. PD-1 blockade can mediate tumor regression in a substantial proportion of patients with melanoma, but it is not known whether this is associated with extended survival or maintenance of response after treatment is discontinued. PATIENTS AND METHODS: Patients with advanced melanoma (N = 107) enrolled between 2008 and 2012 received intravenous nivolumab in an outpatient setting every 2 weeks for up to 96 weeks and were observed for overall survival, long-term safety, and response duration after treatment discontinuation. RESULTS: Median overall survival in nivolumab-treated patients (62% with two to five prior systemic therapies) was 16.8 months, and 1- and 2-year survival rates were 62% and 43%, respectively. Among 33 patients with objective tumor regressions (31%), the Kaplan-Meier estimated median response duration was 2 years. Seventeen patients discontinued therapy for reasons other than disease progression, and 12 (71%) of 17 maintained responses off-therapy for at least 16 weeks (range, 16 to 56+ weeks). Objective response and toxicity rates were similar to those reported previously; in an extended analysis of all 306 patients treated on this trial (including those with other cancer types), exposure-adjusted toxicity rates were not cumulative. CONCLUSION: Overall survival following nivolumab treatment in patients with advanced treatment-refractory melanoma compares favorably with that in literature studies of similar patient populations. Responses were durable and persisted after drug discontinuation. Long-term safety was acceptable. Ongoing randomized clinical trials will further assess the impact of nivolumab therapy on overall survival in patients with metastatic melanoma.

3 Clinical Trial Durable cancer regression off-treatment and effective reinduction therapy with an anti-PD-1 antibody. 2013

Lipson, Evan J / Sharfman, William H / Drake, Charles G / Wollner, Ira / Taube, Janis M / Anders, Robert A / Xu, Haiying / Yao, Sheng / Pons, Alice / Chen, Lieping / Pardoll, Drew M / Brahmer, Julie R / Topalian, Suzanne L. ·Department of Oncology, Johns Hopkins University School of Medicine and Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD 21287, USA. evanlipson@jhmi.edu ·Clin Cancer Res · Pubmed #23169436.

ABSTRACT: PURPOSE: Results from the first-in-human phase I trial of the anti-programmed death-1 (PD-1) antibody BMS-936558 in patients with treatment-refractory solid tumors, including safety, tolerability, pharmacodynamics, and immunologic correlates, have been previously reported. Here, we provide long-term follow-up on three patients from that trial who sustained objective tumor regressions off therapy, and test the hypothesis that reinduction therapy for late tumor recurrence can be effective. EXPERIMENTAL DESIGN: Three patients with colorectal cancer, renal cell cancer, and melanoma achieved objective responses on an intermittent dosing regimen of BMS-936558. Following cessation of therapy, patients were followed for more than 3 years. A patient with melanoma who experienced a prolonged partial regression followed by tumor recurrence received reinduction therapy. RESULTS: A patient with colorectal cancer experienced a complete response, which is ongoing after 3 years. A patient with renal cell cancer experienced a partial response lasting 3 years off therapy, which converted to a complete response, which is ongoing at 12 months. A patient with melanoma achieved a partial response that was stable for 16 months off therapy; recurrent disease was successfully treated with reinduction anti-PD-1 therapy. CONCLUSION: These data represent the most prolonged observation to date of patients with solid tumors responding to anti-PD-1 immunotherapy and the first report of successful reinduction therapy following delayed tumor progression. They underscore the potential for immune checkpoint blockade with anti-PD-1 to reset the equilibrium between tumor and the host immune system.

4 Clinical Trial Safety and activity of anti-PD-L1 antibody in patients with advanced cancer. 2012

Brahmer, Julie R / Tykodi, Scott S / Chow, Laura Q M / Hwu, Wen-Jen / Topalian, Suzanne L / Hwu, Patrick / Drake, Charles G / Camacho, Luis H / Kauh, John / Odunsi, Kunle / Pitot, Henry C / Hamid, Omid / Bhatia, Shailender / Martins, Renato / Eaton, Keith / Chen, Shuming / Salay, Theresa M / Alaparthy, Suresh / Grosso, Joseph F / Korman, Alan J / Parker, Susan M / Agrawal, Shruti / Goldberg, Stacie M / Pardoll, Drew M / Gupta, Ashok / Wigginton, Jon M. ·Johns Hopkins University School of Medicine and the Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD 21231, USA. ·N Engl J Med · Pubmed #22658128.

ABSTRACT: BACKGROUND: Programmed death 1 (PD-1) protein, a T-cell coinhibitory receptor, and one of its ligands, PD-L1, play a pivotal role in the ability of tumor cells to evade the host's immune system. Blockade of interactions between PD-1 and PD-L1 enhances immune function in vitro and mediates antitumor activity in preclinical models. METHODS: In this multicenter phase 1 trial, we administered intravenous anti-PD-L1 antibody (at escalating doses ranging from 0.3 to 10 mg per kilogram of body weight) to patients with selected advanced cancers. Anti-PD-L1 antibody was administered every 14 days in 6-week cycles for up to 16 cycles or until the patient had a complete response or confirmed disease progression. RESULTS: As of February 24, 2012, a total of 207 patients--75 with non-small-cell lung cancer, 55 with melanoma, 18 with colorectal cancer, 17 with renal-cell cancer, 17 with ovarian cancer, 14 with pancreatic cancer, 7 with gastric cancer, and 4 with breast cancer--had received anti-PD-L1 antibody. The median duration of therapy was 12 weeks (range, 2 to 111). Grade 3 or 4 toxic effects that investigators considered to be related to treatment occurred in 9% of patients. Among patients with a response that could be evaluated, an objective response (a complete or partial response) was observed in 9 of 52 patients with melanoma, 2 of 17 with renal-cell cancer, 5 of 49 with non-small-cell lung cancer, and 1 of 17 with ovarian cancer. Responses lasted for 1 year or more in 8 of 16 patients with at least 1 year of follow-up. CONCLUSIONS: Antibody-mediated blockade of PD-L1 induced durable tumor regression (objective response rate of 6 to 17%) and prolonged stabilization of disease (rates of 12 to 41% at 24 weeks) in patients with advanced cancers, including non-small-cell lung cancer, melanoma, and renal-cell cancer. (Funded by Bristol-Myers Squibb and others; ClinicalTrials.gov number, NCT00729664.).

5 Clinical Trial Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. 2012

Topalian, Suzanne L / Hodi, F Stephen / Brahmer, Julie R / Gettinger, Scott N / Smith, David C / McDermott, David F / Powderly, John D / Carvajal, Richard D / Sosman, Jeffrey A / Atkins, Michael B / Leming, Philip D / Spigel, David R / Antonia, Scott J / Horn, Leora / Drake, Charles G / Pardoll, Drew M / Chen, Lieping / Sharfman, William H / Anders, Robert A / Taube, Janis M / McMiller, Tracee L / Xu, Haiying / Korman, Alan J / Jure-Kunkel, Maria / Agrawal, Shruti / McDonald, Daniel / Kollia, Georgia D / Gupta, Ashok / Wigginton, Jon M / Sznol, Mario. ·Department of Surgery, Johns Hopkins University School of Medicine and the Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD 21287, USA. stopali1@jhmi.edu ·N Engl J Med · Pubmed #22658127.

ABSTRACT: BACKGROUND: Blockade of programmed death 1 (PD-1), an inhibitory receptor expressed by T cells, can overcome immune resistance. We assessed the antitumor activity and safety of BMS-936558, an antibody that specifically blocks PD-1. METHODS: We enrolled patients with advanced melanoma, non-small-cell lung cancer, castration-resistant prostate cancer, or renal-cell or colorectal cancer to receive anti-PD-1 antibody at a dose of 0.1 to 10.0 mg per kilogram of body weight every 2 weeks. Response was assessed after each 8-week treatment cycle. Patients received up to 12 cycles until disease progression or a complete response occurred. RESULTS: A total of 296 patients received treatment through February 24, 2012. Grade 3 or 4 drug-related adverse events occurred in 14% of patients; there were three deaths from pulmonary toxicity. No maximum tolerated dose was defined. Adverse events consistent with immune-related causes were observed. Among 236 patients in whom response could be evaluated, objective responses (complete or partial responses) were observed in those with non-small-cell lung cancer, melanoma, or renal-cell cancer. Cumulative response rates (all doses) were 18% among patients with non-small-cell lung cancer (14 of 76 patients), 28% among patients with melanoma (26 of 94 patients), and 27% among patients with renal-cell cancer (9 of 33 patients). Responses were durable; 20 of 31 responses lasted 1 year or more in patients with 1 year or more of follow-up. To assess the role of intratumoral PD-1 ligand (PD-L1) expression in the modulation of the PD-1-PD-L1 pathway, immunohistochemical analysis was performed on pretreatment tumor specimens obtained from 42 patients. Of 17 patients with PD-L1-negative tumors, none had an objective response; 9 of 25 patients (36%) with PD-L1-positive tumors had an objective response (P=0.006). CONCLUSIONS: Anti-PD-1 antibody produced objective responses in approximately one in four to one in five patients with non-small-cell lung cancer, melanoma, or renal-cell cancer; the adverse-event profile does not appear to preclude its use. Preliminary data suggest a relationship between PD-L1 expression on tumor cells and objective response. (Funded by Bristol-Myers Squibb and others; ClinicalTrials.gov number, NCT00730639.).

6 Clinical Trial Phase I study of single-agent anti-programmed death-1 (MDX-1106) in refractory solid tumors: safety, clinical activity, pharmacodynamics, and immunologic correlates. 2010

Brahmer, Julie R / Drake, Charles G / Wollner, Ira / Powderly, John D / Picus, Joel / Sharfman, William H / Stankevich, Elizabeth / Pons, Alice / Salay, Theresa M / McMiller, Tracee L / Gilson, Marta M / Wang, Changyu / Selby, Mark / Taube, Janis M / Anders, Robert / Chen, Lieping / Korman, Alan J / Pardoll, Drew M / Lowy, Israel / Topalian, Suzanne L. ·Johns Hopkins University School of Medicine, and the Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD, USA. ·J Clin Oncol · Pubmed #20516446.

ABSTRACT: PURPOSE: Programmed death-1 (PD-1), an inhibitory receptor expressed on activated T cells, may suppress antitumor immunity. This phase I study sought to determine the safety and tolerability of anti-PD-1 blockade in patients with treatment-refractory solid tumors and to preliminarily assess antitumor activity, pharmacodynamics, and immunologic correlates. PATIENTS AND METHODS: Thirty-nine patients with advanced metastatic melanoma, colorectal cancer (CRC), castrate-resistant prostate cancer, non-small-cell lung cancer (NSCLC), or renal cell carcinoma (RCC) received a single intravenous infusion of anti-PD-1 (MDX-1106) in dose-escalating six-patient cohorts at 0.3, 1, 3, or 10 mg/kg, followed by a 15-patient expansion cohort at 10 mg/kg. Patients with evidence of clinical benefit at 3 months were eligible for repeated therapy. RESULTS: Anti-PD-1 was well tolerated: one serious adverse event, inflammatory colitis, was observed in a patient with melanoma who received five doses at 1 mg/kg. One durable complete response (CRC) and two partial responses (PRs; melanoma, RCC) were seen. Two additional patients (melanoma, NSCLC) had significant lesional tumor regressions not meeting PR criteria. The serum half-life of anti-PD-1 was 12 to 20 days. However, pharmacodynamics indicated a sustained mean occupancy of > 70% of PD-1 molecules on circulating T cells > or = 2 months following infusion, regardless of dose. In nine patients examined, tumor cell surface B7-H1 expression appeared to correlate with the likelihood of response to treatment. CONCLUSION: Blocking the PD-1 immune checkpoint with intermittent antibody dosing is well tolerated and associated with evidence of antitumor activity. Exploration of alternative dosing regimens and combinatorial therapies with vaccines, targeted therapies, and/or other checkpoint inhibitors is warranted.

7 Article Concurrent Immune Checkpoint Inhibitors and Stereotactic Radiosurgery for Brain Metastases in Non-Small Cell Lung Cancer, Melanoma, and Renal Cell Carcinoma. 2018

Chen, Linda / Douglass, Jacqueline / Kleinberg, Lawrence / Ye, Xiaobu / Marciscano, Ariel E / Forde, Patrick M / Brahmer, Julie / Lipson, Evan / Sharfman, William / Hammers, Hans / Naidoo, Jarushka / Bettegowda, Chetan / Lim, Michael / Redmond, Kristin J. ·Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins Hospital, Baltimore, Maryland. · Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins Hospital, Baltimore, Maryland; Johns Hopkins University School of Medicine, Baltimore, Maryland. · Department of Neurosurgery, Johns Hopkins Hospital, Baltimore, Maryland; Department of Oncology Biostatistics and Bioinformatics, Johns Hopkins School of Medicine, Baltimore, Maryland. · Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Hospital, Baltimore, Maryland. · Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Hospital, Baltimore, Maryland; Department of Medical and Surgical Oncology, Harold C. Simmons Comprehensive Cancer Center, University of Texas Southwestern, Dallas, Texas. · Department of Neurosurgery, Johns Hopkins Hospital, Baltimore, Maryland. · Department of Neurosurgery, Johns Hopkins Hospital, Baltimore, Maryland. Electronic address: mlim3@jhmi.edu. · Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins Hospital, Baltimore, Maryland. Electronic address: kjanson3@jhmi.edu. ·Int J Radiat Oncol Biol Phys · Pubmed #29485071.

ABSTRACT: PURPOSE: To characterize the effect of concurrent stereotactic radiosurgery-stereotactic radiation therapy (SRS-SRT) and immune checkpoint inhibitors on patient outcomes and safety in patients with brain metastases (BMs). METHODS AND MATERIALS: We retrospectively identified metastatic non-small cell lung cancer, melanoma, and renal cell carcinoma patients who had BMs treated with SRS-SRT from 2010 to 2016 without prior whole-brain radiation therapy. We included SRS-SRT patients who were treated with anti-cytotoxic T-lymphocyte-associated protein 4 (ipilimumab) and anti-programmed cell death protein 1 receptor (nivolumab, pembrolizumab). Patients who were given immune checkpoint inhibitors on active or unreported clinical trials were excluded, and concurrent immune checkpoint inhibition (ICI) was defined as ICI given within 2 weeks of SRS-SRT. Patients were managed with SRS-SRT, SRS-SRT with nonconcurrent ICI, or SRS-SRT with concurrent ICI. Progression-free survival and overall survival (OS) were estimated using Kaplan-Meier survival curves, and Cox proportional hazards models were used for multivariate analysis. Logistic regression was used to identify predictors of acute neurologic toxicity, immune-related adverse events, and new BMs. RESULTS: A total of 260 patients were treated with SRS-SRT to 623 BMs. Of these patients, 181 were treated with SRS-SRT alone, whereas 79 received SRS-SRT and ICI, 35% of whom were treated with concurrent SRS-SRT and ICI. Concurrent ICI was not associated with increased rates of immune-related adverse events or acute neurologic toxicity and predicted for a decreased likelihood of the development of ≥3 new BMs after SRS-SRT (P=.045; odds ratio, 0.337). Median OS for patients treated with SRS-SRT, SRS-SRT with nonconcurrent ICI, and SRS-SRT with concurrent ICI was 12.9 months, 14.5 months, and 24.7 months, respectively. SRS-SRT with concurrent ICI was associated with improved OS compared with SRS-SRT alone (P=.002; hazard ratio [HR], 2.69) and compared with nonconcurrent SRS-SRT and ICI (P=.006; HR, 2.40) on multivariate analysis. The OS benefit of concurrent SRS-SRT and ICI was significant in comparison with patients treated with SRS-SRT before ICI (P=.002; HR, 3.82) or after ICI (P=.021; HR, 2.64). CONCLUSIONS: Delivering SRS-SRT with concurrent ICI may be associated with a decreased incidence of new BMs and favorable survival outcomes without increased rates of adverse events.

8 Minor Reply: Regulatory T cells-an important target for cancer immunotherapy. 2014

Drake, Charles G / Lipson, Evan J / Brahmer, Julie R. ·Department of Oncology, Johns Hopkins University, 1650 Orleans Street, Baltimore, MD 21231, USA. ·Nat Rev Clin Oncol · Pubmed #24781414.

ABSTRACT: -- No abstract --