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Article: Identifying and addressing the toxicity of checkpoint inhibitors in lung cancer.

Brahmer, Julie R

Clinical advances in hematology & oncology : H&O

2016 Volume 14, Issue 3, Page(s) 165–167

MeSH term(s)	Antineoplastic Agents/adverse effects ; Antineoplastic Agents/therapeutic use ; Autoimmune Diseases/diagnosis ; Autoimmune Diseases/etiology ; B7-H1 Antigen/antagonists & inhibitors ; CTLA-4 Antigen/antagonists & inhibitors ; Humans ; Immunotherapy/adverse effects ; Lung Neoplasms/complications ; Lung Neoplasms/drug therapy ; Lung Neoplasms/immunology ; Lung Neoplasms/metabolism ; Molecular Targeted Therapy/adverse effects ; Programmed Cell Death 1 Receptor/antagonists & inhibitors
Chemical Substances	Antineoplastic Agents ; B7-H1 Antigen ; CTLA-4 Antigen ; Programmed Cell Death 1 Receptor
Language	English
Publishing date	2016-03
Publishing country	United States
Document type	Interview
ZDB-ID	2271951-9
ISSN	1543-0790
ISSN	1543-0790
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Article ; Online: Incidence, Correlates, and Prognostic Significance of Mixed Response in Advanced Non-small Cell Lung Cancer.

Gerber, David E / Wang, Yating / Ramalingam, Suresh S / Bhalla, Sheena / Sun, Zhuoxin / Borghaei, Hossein / Brahmer, Julie R / Schiller, Joan H

The oncologist

2024 Volume 29, Issue 4, Page(s) 342–349

Abstract: Background: Mixed response (MR), a scenario featuring discordant tumor changes, has been reported primarily with targeted therapies or immunotherapy. We determined the incidence and prognostic significance of MR in advanced non-small cell lung cancer ( ... ...

Abstract	Background: Mixed response (MR), a scenario featuring discordant tumor changes, has been reported primarily with targeted therapies or immunotherapy. We determined the incidence and prognostic significance of MR in advanced non-small cell lung cancer (NSCLC) treated with cytotoxic chemotherapy. Patients and methods: We analyzed patient-level data from ECOG-ACRIN E5508 (carboplatin-paclitaxel + bevacizumab induction followed by randomization to maintenance therapy regimens). For patients with at least 2 target lesions and available measurements after cycle 2, we characterized response as homogeneous response (HR, similar behavior of all lesions), MR (similar behavior but >30% difference in magnitude of best and least responding lesions), or true mixed response (TMR, best and least responding lesions showing different behavior: ≥10% growth versus ≥10% shrinkage). We compared category characteristics using Mann-Whitney U and Chi-square tests, and overall survival (OS) using log-rank test and Cox models. Results: Among 965 evaluable patients, HR occurred in 609 patients (63%), MR in 208 (22%), and TMR in 148 (15%). Median OS was 13.6 months for HR, 12.0 months for MR, and 7.6 months for TMR (P < .001). Compared to HR, TMR had inferior OS among stable disease cases (HR 1.62; 95% CI, 1.23-2.12; P < .001) and a trend toward inferior OS among progressive disease cases (HR 1.39; 95% CI, 0.83-2.33; P = .2). In multivariate analysis, TMR was associated with worse OS (HR 1.48; 95% CI, 1.22-1.79; P < .001). Conclusion: True mixed response occurs in a substantial minority of lung cancer cases treated with chemotherapy and independently confers poor prognosis.
MeSH term(s)	Humans ; Carcinoma, Non-Small-Cell Lung/drug therapy ; Carcinoma, Non-Small-Cell Lung/epidemiology ; Lung Neoplasms/drug therapy ; Lung Neoplasms/epidemiology ; Prognosis ; Incidence ; Proportional Hazards Models ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Carboplatin/therapeutic use ; Paclitaxel/therapeutic use
Chemical Substances	Carboplatin (BG3F62OND5) ; Paclitaxel (P88XT4IS4D)
Language	English
Publishing date	2024-01-11
Publishing country	England
Document type	Journal Article
ZDB-ID	1409038-7
ISSN	1549-490X ; 1083-7159
ISSN (online)	1549-490X
ISSN	1083-7159
DOI	10.1093/oncolo/oyad335
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Zs.A 4845: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Checkpoint Blockade in Lung Cancer With Driver Mutation: Choose the Road Wisely.

Calles, Antonio / Riess, Jonathan W / Brahmer, Julie R

American Society of Clinical Oncology educational book. American Society of Clinical Oncology. Annual Meeting

2020 Volume 40, Page(s) 372–384

Abstract: Immune checkpoint blockade with PD-(L)1 antibodies has revolutionized the treatment of advanced non-small cell lung cancer (NSCLC). Similarly, the identification and targeting of oncogene drivers in metastatic NSCLC has dramatically improved patient ... ...

Abstract	Immune checkpoint blockade with PD-(L)1 antibodies has revolutionized the treatment of advanced non-small cell lung cancer (NSCLC). Similarly, the identification and targeting of oncogene drivers in metastatic NSCLC has dramatically improved patient outcomes with an expanding list of potentially actionable alterations and targeted therapies. Many of these molecular aberrations are more common in patients with little or no smoking history and adenocarcinoma histology. Certain molecular subsets of NSCLC, though gaining greatly from targeted therapy approaches, may derive less benefit from immune checkpoint blockade. The optimal identification, targeting, and sequencing of targeted therapies, immunotherapy, and chemotherapy are essential to continue to improve patient outcomes in advanced NSCLC. Herein, we review the role of immunotherapy in locally advanced and metastatic disease for patients with actionable driver alterations. Never-smoking patients have a high probability of having lung cancer that harbors one of these molecular aberrations that can be matched to a tyrosine kinase inhibitor with greatly improved clinical outcomes. Some of these patients with driver mutations may derive less benefit from immune checkpoint inhibitor approaches (either alone or combined with chemotherapy), especially compared with smoking-associated NSCLC. Given that PD-1 blockade alone or with platinum-based chemotherapy is the de facto first-line therapy (depending on level of PD-L1 expression) for nontargetable metastatic NSCLC, we also review treatment in never-smoking patients for whom molecular testing results are pending and the likelihood of identifying a driver mutation is high.
MeSH term(s)	Carcinoma, Non-Small-Cell Lung/drug therapy ; Carcinoma, Non-Small-Cell Lung/genetics ; Carcinoma, Non-Small-Cell Lung/immunology ; Carcinoma, Non-Small-Cell Lung/pathology ; Humans ; Immune Checkpoint Inhibitors/therapeutic use ; Immunotherapy ; Lung Neoplasms/drug therapy ; Lung Neoplasms/genetics ; Lung Neoplasms/immunology ; Lung Neoplasms/pathology ; Mutation
Chemical Substances	Immune Checkpoint Inhibitors
Language	English
Publishing date	2020-05-11
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	2431126-1
ISSN	1548-8756 ; 1548-8748
ISSN (online)	1548-8756
ISSN	1548-8748
DOI	10.1200/EDBK_280795
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Harnessing the immune system for the treatment of non-small-cell lung cancer.

Brahmer, Julie R

Journal of clinical oncology : official journal of the American Society of Clinical Oncology

2013 Volume 31, Issue 8, Page(s) 1021–1028

Abstract: Over the last several years, new therapeutic targets have emerged in immunotherapy, particularly the immune checkpoint pathways. Blocking inhibitory pathways via monoclonal antibodies, such as the anti-cytotoxic T-lymphocyte antigen-4 antibody ( ... ...

Abstract	Over the last several years, new therapeutic targets have emerged in immunotherapy, particularly the immune checkpoint pathways. Blocking inhibitory pathways via monoclonal antibodies, such as the anti-cytotoxic T-lymphocyte antigen-4 antibody (ipilimumab), anti-programmed cell death-1 antibody (BMS-936558), and anti-programmed cell death-1 ligand antibody (BMS-936559), has the ability to break down the shield that tumors co-opt for their defense. Vaccines are able to help the immune system develop immune memory that can have long-lasting, tumor-specific effects. Newer vaccines, particularly the tumor cell vaccine, belagenpumatucel-L, and the antigen-specific vaccines, melanoma-associated antigen-A3, liposomal BLP-25, TG4010, and recombinant human epidermal growth factor, are being evaluated in some of the largest trials ever attempted in lung cancer therapy. These therapies alone or in combination may hold the key to making immunotherapy a reality in the treatment of lung cancer.
MeSH term(s)	Antineoplastic Agents/immunology ; Cancer Vaccines/immunology ; Cancer Vaccines/therapeutic use ; Carcinoma, Non-Small-Cell Lung/immunology ; Carcinoma, Non-Small-Cell Lung/therapy ; Clinical Trials as Topic ; Humans ; Immunotherapy/methods ; Lung Neoplasms/immunology ; Lung Neoplasms/therapy ; T-Lymphocytes/immunology
Chemical Substances	Antineoplastic Agents ; Cancer Vaccines
Language	English
Publishing date	2013-03-10
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	604914-x
ISSN	1527-7755 ; 0732-183X
ISSN (online)	1527-7755
ISSN	0732-183X
DOI	10.1200/JCO.2012.45.8703
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Zs.A 1847: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Immune checkpoint blockade: the hope for immunotherapy as a treatment of lung cancer?

Brahmer, Julie R

Seminars in oncology

2013 Volume 41, Issue 1, Page(s) 126–132

Abstract: Over the past 20 years, immunotherapy has not played a role in the treatment of lung cancer outside of clinical trials. Early trials with vaccines yielded promising results, but phase III trials have yet to show an improvement in survival. Recently, ... ...

Abstract	Over the past 20 years, immunotherapy has not played a role in the treatment of lung cancer outside of clinical trials. Early trials with vaccines yielded promising results, but phase III trials have yet to show an improvement in survival. Recently, immune checkpoint pathway inhibitors have yielded exciting and consistent activity across this class of antibodies. However, phase III trials are now ongoing. Currently, the hope of bringing immunotherapy to lung cancer patients lies in this class of drugs. Only time will show us if these antibodies will yield an improvement in long-term survival. This review will focus on checkpoint pathway inhibitors that have completed early-phase trials.
MeSH term(s)	Animals ; Antibodies, Monoclonal/therapeutic use ; Cancer Vaccines/therapeutic use ; Humans ; Immunotherapy ; Lung Neoplasms/drug therapy ; Lung Neoplasms/immunology
Chemical Substances	Antibodies, Monoclonal ; Cancer Vaccines
Language	English
Publishing date	2013-12-12
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	189220-4
ISSN	1532-8708 ; 0093-7754
ISSN (online)	1532-8708
ISSN	0093-7754
DOI	10.1053/j.seminoncol.2013.12.014
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Article ; Online: Derivation of CD8

Topper, Michael J / Anagnostou, Valsamo / Marrone, Kristen A / Velculescu, Victor E / Jones, Peter A / Brahmer, Julie R / Baylin, Stephen B / Hostetter, Galen H

iScience

2023 Volume 26, Issue 7, Page(s) 107095

Abstract: Non-small-cell lung cancer remains a deadly form of human cancer even in the era of immunotherapy with existing immunotherapy strategies currently only benefiting a minority of patients. Therefore, the derivation of treatment options, which might extend ... ...

Abstract	Non-small-cell lung cancer remains a deadly form of human cancer even in the era of immunotherapy with existing immunotherapy strategies currently only benefiting a minority of patients. Therefore, the derivation of treatment options, which might extend the promise of immunotherapy to more patients, remains of paramount importance. Here, we define using TCGA lung squamous and lung adenocarcinoma RNAseq datasets a significant correlation between epigenetic therapy actionable interferon genes with both predicted tumor immune score generally, and CD8A specifically. IHC validation using primary sample tissue microarrays confirmed a pronounced positive association between CD8
Language	English
Publishing date	2023-06-10
Publishing country	United States
Document type	Journal Article
ISSN	2589-0042
ISSN (online)	2589-0042
DOI	10.1016/j.isci.2023.107095
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Pembrolizumab in Non-Small-Cell Lung Cancer.

Reck, Martin / Brahmer, Julie R

The New England journal of medicine

2017 Volume 376, Issue 10, Page(s) 997

MeSH term(s)	Antibodies, Monoclonal ; Carcinoma, Non-Small-Cell Lung ; Humans
Chemical Substances	Antibodies, Monoclonal
Language	English
Publishing date	2017--09
Publishing country	United States
Document type	Letter ; Comment
ZDB-ID	207154-x
ISSN	1533-4406 ; 0028-4793
ISSN (online)	1533-4406
ISSN	0028-4793
DOI	10.1056/NEJMc1615559
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Article: PD-1-targeted immunotherapy: recent clinical findings.

Brahmer, Julie R

Clinical advances in hematology & oncology : H&O

2012 Volume 10, Issue 10, Page(s) 674–675

MeSH term(s)	Aged ; Antibodies, Monoclonal/immunology ; Antibodies, Monoclonal/therapeutic use ; Antineoplastic Agents/immunology ; Antineoplastic Agents/therapeutic use ; B7-H1 Antigen/genetics ; B7-H1 Antigen/immunology ; Carcinoma, Non-Small-Cell Lung/immunology ; Carcinoma, Non-Small-Cell Lung/mortality ; Carcinoma, Non-Small-Cell Lung/therapy ; Clinical Trials as Topic ; Drug Administration Schedule ; Female ; Gene Expression ; Humans ; Immunoglobulin G/immunology ; Immunotherapy ; Lung Neoplasms/immunology ; Lung Neoplasms/mortality ; Lung Neoplasms/therapy ; Middle Aged ; Molecular Targeted Therapy ; Programmed Cell Death 1 Receptor/antagonists & inhibitors ; Programmed Cell Death 1 Receptor/genetics ; Programmed Cell Death 1 Receptor/immunology ; Survival Analysis
Chemical Substances	Antibodies, Monoclonal ; Antineoplastic Agents ; B7-H1 Antigen ; CD274 protein, human ; Immunoglobulin G ; PDCD1 protein, human ; Programmed Cell Death 1 Receptor ; nivolumab (31YO63LBSN)
Language	English
Publishing date	2012-10
Publishing country	United States
Document type	Journal Article
ZDB-ID	2271951-9
ISSN	1543-0790
ISSN	1543-0790
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Article ; Online: Outcomes of immunotherapy-related hepatotoxicity from a multi-disciplinary toxicity team

Fan, Christopher / Kim, Ahyoung / Li, Xuguang / Naidoo, Jarushka / Cappelli, Laura C. / Brahmer, Julie R. / Anders, Robert A. / Kim, Amy K.

J Cancer Res Clin Oncol. 2023 Feb., v. 149, no. 2, p. 877-883

2023 , Page(s) 877–883

Abstract: BACKGROUND: Despite the efficacy of immune checkpoint inhibitors (ICIs), adverse events including hepatotoxicity limit their ongoing use. We investigated the outcomes and management of patients with immune-mediated hepatitis (IMH) and clinical predictors ...

Abstract	BACKGROUND: Despite the efficacy of immune checkpoint inhibitors (ICIs), adverse events including hepatotoxicity limit their ongoing use. We investigated the outcomes and management of patients with immune-mediated hepatitis (IMH) and clinical predictors of toxicity resolution. METHODS: Patients referred to our multidisciplinary immunotherapy-related toxicity group from August 2017 to December 2020 for IMH were evaluated. Toxicity was defined according to CTCAEv4.0. IMH resolution was defined as liver enzyme normalization after steroid initiation. RESULTS: Thirty-three patients were included in the study, 62% female, and 71% Caucasian. The most common ICI used was PD-1/PD-L1 (76%). Peak IMH occurred at a median of 89 [45,193] days, for which most patients received 1–2 mg/kg/day prednisone equivalent with 35% requiring MMF. Median follow-up was 123 [33,472] days with IMH resolution seen in 48% of patients at a median of 111 [41,214] days. While high-dose steroid use was not associated with IMH resolution, liver enzyme improvement one week after steroids predicted resolution in univariate analysis (p = 0.041). All 11 patients without IMH resolution died from cancer progression or complications with three patients having acute liver failure. Available liver biopsies showed bile duct injury, with varying degrees of portal and lobular inflammation. CONCLUSION: IMH improvement one week after steroid initiation may predict ultimate IMH resolution.
Keywords	bile ducts ; enzymes ; females ; hepatitis ; hepatotoxicity ; inflammation ; liver ; liver failure ; neoplasm progression ; prednisone ; steroid hormones
Language	English
Dates of publication	2023-02
Size	p. 877-883
Publishing place	Springer Berlin Heidelberg
Document type	Article ; Online
ZDB-ID	134792-5
ISSN	1432-1335 ; 0171-5216 ; 0084-5353 ; 0943-9382
ISSN (online)	1432-1335
ISSN	0171-5216 ; 0084-5353 ; 0943-9382
DOI	10.1007/s00432-022-04299-1
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Challenge of Rechallenge: When to Resume Immunotherapy Following an Immune-Related Adverse Event.

Nakajima, Erica C / Lipson, Evan J / Brahmer, Julie R

Journal of clinical oncology : official journal of the American Society of Clinical Oncology

2019 Volume 37, Issue 30, Page(s) 2714–2718

MeSH term(s)	Aged ; Drug-Related Side Effects and Adverse Reactions/drug therapy ; Drug-Related Side Effects and Adverse Reactions/immunology ; Female ; Humans ; Immunotherapy/methods ; Male ; Middle Aged
Language	English
Publishing date	2019-08-28
Publishing country	United States
Document type	Case Reports ; Journal Article
ZDB-ID	604914-x
ISSN	1527-7755 ; 0732-183X
ISSN (online)	1527-7755
ISSN	0732-183X
DOI	10.1200/JCO.19.01623
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