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Melanoma: HELP
Articles by Adil I. Daud
Based on 74 articles published since 2008
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Between 2008 and 2019, A. Daud wrote the following 74 articles about Melanoma.
 
+ Citations + Abstracts
Pages: 1 · 2 · 3
1 Guideline Melanoma, version 4.2014. 2014

Coit, Daniel G / Thompson, John A / Andtbacka, Robert / Anker, Christopher J / Bichakjian, Christopher K / Carson, William E / Daniels, Gregory A / Daud, Adil / Dimaio, Dominick / Fleming, Martin D / Gonzalez, Rene / Guild, Valerie / Halpern, Allan C / Hodi, F Stephen / Kelley, Mark C / Khushalani, Nikhil I / Kudchadkar, Ragini R / Lange, Julie R / Martini, Mary C / Olszanski, Anthony J / Ross, Merrick I / Salama, April / Swetter, Susan M / Tanabe, Kenneth K / Trisal, Vijay / Urist, Marshall M / McMillian, Nicole R / Ho, Maria / Anonymous5170793. ·From 1Memorial Sloan-Kettering Cancer Center; 2Fred Hutchinson Cancer Research Center/Seattle Cancer Care Alliance; 3Huntsman Cancer Institute at the University of Utah; 4University of Michigan Comprehensive Cancer Center; 5The Ohio State University Comprehensive Cancer Center - James Cancer Hospital and Solove Research Institute; 6UC San Diego Moores Cancer Center; 7UCSF Helen Diller Family Comprehensive Cancer Center; 8Fred & Pamela Buffett Cancer Center at The Nebraska Medical Center; 9St. Jude Children's Research Hospital/The University of Tennessee Health Science Center; 10University of Colorado Cancer Center; 11Aim at Melanoma; 12Dana-Farber/Brigham and Women's Cancer Center; 13Vanderbilt-Ingram Cancer Center; 14Roswell Park Cancer Institute; 15Moffitt Cancer Center; 16The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins; 17Robert H. Lurie Comprehensive Cancer Center of Northwestern University; 18Fox Chase Cancer Center; 19The University of Texas MD Anderson Cancer Center; 20Duke Cancer Institute; 21Stanford Cancer Institute; 22Massachusetts General Hospital Cancer Center; 23City of Hope Comprehensive Cancer Center; 24University of Alabama at Birmingham Comprehensive Cancer Center; and 25National Comprehensive Cancer Network. ·J Natl Compr Canc Netw · Pubmed #24812131.

ABSTRACT: The NCCN Guidelines for Melanoma provide multidisciplinary recommendations for the management of patients with melanoma. These NCCN Guidelines Insights highlight notable recent updates. Dabrafenib and trametinib, either as monotherapy (category 1) or combination therapy, have been added as systemic options for patients with unresectable metastatic melanoma harboring BRAF V600 mutations. Controversy continues regarding the value of adjuvant radiation for patients at high risk of nodal relapse. This is reflected in the category 2B designation to consider adjuvant radiation following lymphadenectomy for stage III melanoma with clinically positive nodes or recurrent disease.

2 Guideline Melanoma, version 2.2013: featured updates to the NCCN guidelines. 2013

Coit, Daniel G / Andtbacka, Robert / Anker, Christopher J / Bichakjian, Christopher K / Carson, William E / Daud, Adil / Dimaio, Dominick / Fleming, Martin D / Guild, Valerie / Halpern, Allan C / Hodi, F Stephen / Kelley, Mark C / Khushalani, Nikhil I / Kudchadkar, Ragini R / Lange, Julie R / Lind, Anne / Martini, Mary C / Olszanski, Anthony J / Pruitt, Scott K / Ross, Merrick I / Swetter, Susan M / Tanabe, Kenneth K / Thompson, John A / Trisal, Vijay / Urist, Marshall M / McMillian, Nicole / Ho, Maria / Anonymous4310755. ·Memorial Sloan-Kettering Cancer Center. ·J Natl Compr Canc Netw · Pubmed #23584343.

ABSTRACT: The NCCN Guidelines for Melanoma provide multidisciplinary recommendations on the clinical management of patients with melanoma. This NCCN Guidelines Insights report highlights notable recent updates. Foremost of these is the exciting addition of the novel agents ipilimumab and vemurafenib for treatment of advanced melanoma. The NCCN panel also included imatinib as a treatment for KIT-mutated tumors and pegylated interferon alfa-2b as an option for adjuvant therapy. Also important are revisions to the initial stratification of early-stage lesions based on the risk of sentinel lymph node metastases, and revised recommendations on the use of sentinel lymph node biopsy for low-risk groups. Finally, the NCCN panel reached clinical consensus on clarifying the role of imaging in the workup of patients with melanoma.

3 Guideline Melanoma. 2012

Coit, Daniel G / Andtbacka, Robert / Anker, Christopher J / Bichakjian, Christopher K / Carson, William E / Daud, Adil / Dilawari, Raza A / Dimaio, Dominick / Guild, Valerie / Halpern, Allan C / Hodi, F Stephen / Kelley, Mark C / Khushalani, Nikhil I / Kudchadkar, Ragini R / Lange, Julie R / Lind, Anne / Martini, Mary C / Olszanski, Anthony J / Pruitt, Scott K / Ross, Merrick I / Swetter, Susan M / Tanabe, Kenneth K / Thompson, John A / Trisal, Vijay / Urist, Marshall M / Anonymous590720. · ·J Natl Compr Canc Netw · Pubmed #22393197.

ABSTRACT: -- No abstract --

4 Editorial BEAM trial: lighting the way ahead? 2012

Daud, Adil I. · ·J Clin Oncol · Pubmed #22124100.

ABSTRACT: -- No abstract --

5 Editorial Melanoma: promising new discoveries and treatment modalities for difficult clinical scenarios. 2008

Zager, Jonathan S / Daud, Adil I. · ·Cancer Control · Pubmed #18596670.

ABSTRACT: -- No abstract --

6 Review Management of Treatment-Related Adverse Events with Agents Targeting the MAPK Pathway in Patients with Metastatic Melanoma. 2017

Daud, Adil / Tsai, Katy. ·University of California San Francisco Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, California, USA Adil.Daud@ucsf.edu. · University of California San Francisco Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, California, USA. ·Oncologist · Pubmed #28526719.

ABSTRACT: Tremendous progress has been made in the clinical landscape of advanced-stage IMPLICATIONS FOR PRACTICE: Targeted therapy with BRAF plus MEK inhibitors has become the standard of care for patients with advanced-stage

7 Review Inhibitors of Cytotoxic T Lymphocyte Antigen 4 and Programmed Death 1/Programmed Death 1 Ligand for Metastatic Melanoma, Dual Versus Monotherapy-Summary of Advances and Future Directions for Studying These Drugs. 2017

Loo, Kimberly / Daud, Adil I. ·From the University of California-San Francisco, San Francisco, CA. ·Cancer J · Pubmed #28114249.

ABSTRACT: Immense progress in the field of cancer immunotherapy has garnered several novel and successful treatments for metastatic melanoma. Beginning with therapies targeting cytotoxic T lymphocyte antigen 4 (CTLA-4), objective response rates, overall survival, and long-term survival were significantly increased when compared with glycoprotein 100 vaccine therapies. Expanding the breadth of therapies aimed to "release the breaks" on the active immune system, anti-programmed death 1 (PD-1) and anti-programmed death 1 ligand (PD-L1) therapies further improved overall survival, progression-free survival, and objective tumor response while exhibiting more favorable safety profiles compared with ipilimumab and to chemotherapy agents. Given the power of these agents as monotherapies, a combination approach sought to combine the anti-CTLA agent ipilimumab and anti-PD-1 agent, nivolumab, to form a double-pronged attack and target several mechanisms within the active immune system. Given the promise in elevated response rates and progression-free survival, the future appears promising along the immunotherapy front. Continuing the push for progress, biomarkers to uncover the profile of responders to the various therapies will become vital in the treatment of metastatic melanoma patients. Here, we highlight the advances of CTLA-4 and PD-1/PD-L1 inhibitors in the metastatic melanoma setting and discuss future directions for uncovering the full potential of these therapies.

8 Review Emerging biomarkers as predictors to anti-PD1/PD-L1 therapies in advanced melanoma. 2016

Loo, Kimberly / Daud, Adil. ·Helen Diller Comprehensive Cancer Center, Department of Melanoma and Cutaneous Oncology, University of California San Francisco, San Francisco, CA 94143, USA. ·Immunotherapy · Pubmed #27349977.

ABSTRACT: Recent advances in the field of cancer immunotherapy have resulted in a surge of new therapies for patients spanning multiple cancer indications. In melanoma alone, several immunotherapies have emerged as promising agents to tackle the aggressive, often refractory disease in the advanced/metastatic setting. The Programmed Cell Death pathway, from which anti-PD-1 and anti-PD-L1 therapies were developed, has shown immense promise. Given the marked success of the PD-1/PD-L1 immunotherapies, several targets have emerged as promising biomarkers, including PD-L1 tumor expression, tumor-infiltrating T-cell markers, dendritic cell markers, TCR sequencing, neoantigens and peripheral blood markers. Highlighted in this review, we examine the recent efforts to identify robust and reliable biomarkers as predictors of response to anti-PD-1/PD-L1 immune checkpoint inhibitors.

9 Review Current and Emerging Perspectives on Immunotherapy for Melanoma. 2015

Daud, Adil. ·HS Clinical Professor, Department of Medicine (Hematology/Oncology), University of California San Francisco, San Francisco, CA; Director, Melanoma Clinical Research, University of California San Francisco Helen Diller Family Comprehensive Cancer Center, San Francisco, CA. Electronic address: Adil.Daud@ucsf.edu. ·Semin Oncol · Pubmed #26598057.

ABSTRACT: Novel immunotherapeutic treatments are aimed at reversing the action of inhibitory pathways that restrain the T-cell-dominated immune-mediated defense against cancer. The first immune-inhibitory protein to be discovered was cytotoxic T-lymphocyte antigen-4 (CTLA-4). The effectiveness of a CTLA-targeted antibody in treating melanoma was an impetus for the use of programmed cell death-1 (PD-1) inhibitors in cancer treatment. Important differences between the use of CTLA-4 inhibitors and PD-1 inhibitors in treatment include the patterns of expression of each receptor and its ligands and sites of action, as CTLA-4 blockade has been noted to provide more global effects, whereas those of PD-1 inhibition are observed at the tumor site. Although each treatment has been associated with impressive benefits in advanced melanoma, recent comparative studies suggest that PD-1 inhibitors may be more effective than CTLA-4 inhibition and that the most optimal results may be observed using both agents in those who can tolerate the increased toxicity that accompanies combination treatment. The most common adverse reactions include skin effects using either CTLA-4-blocking antibody or PD-1 inhibitors, colitis using CTLA-4 blockade, or thyroid disease using PD-1 inhibitors.

10 Review Future of combination therapy with dabrafenib and trametinib in metastatic melanoma. 2015

Zia, Yasaman / Chen, Lawrence / Daud, Adil. ·a 1 UCSF Helen Diller Comprehensive Cancer Center , 1600 Divisadero Street, Room B708, San Francisco, CA 94115, USA +1 20 24 89 19 86 ; +1 41 55 14 69 69 ; yaszia@gmail.com. · b 2 UCSF Helen Diller Comprehensive Cancer Center , 1600 Divisadero Street, Room B708, San Francisco, CA 94115, USA. · c 3 UCSF Helen Diller Comprehensive Cancer Center , 1600 Divisadero Street, Room B708, San Francisco, CA 94115, USA. ·Expert Opin Pharmacother · Pubmed #26331795.

ABSTRACT: INTRODUCTION: Combination therapy with BRAF and MEK inhibitors is a recommended treatment strategy for metastatic melanoma patients with BRAF(V600) mutations. This treatment provides significant response rates and little added toxicity, with relatively improved survival outcomes compared to RAF/MEK inhibitor monotherapy and chemotherapy. AREAS COVERED: This review covers the pharmacology, efficacy, and toxicity data derived from clinical studies of dabrafenib, trametinib , and the combination thereof. The major downfall of combiDT is the limited durability of response, which is largely due to acquired resistance in the MAPK pathway. EXPERT OPINION: Future directions of combiDT concentrate on further combinations with immunotherapy or other targeted inhibitors, referred to triple-agent therapy, which may be essential to improving durability of responses and overcoming resistance.

11 Review The Role of Anti-PD-1/PD-L1 Agents in Melanoma: Progress to Date. 2015

Tsai, Katy K / Daud, Adil I. ·Division of Hematology/Oncology, Department of Medicine, University of California San Francisco (UCSF), Mount Zion A-743, 1600 Divisadero Street, San Francisco, CA, 94143, USA. ·Drugs · Pubmed #25802230.

ABSTRACT: The discovery of immune inhibitory checkpoints has revolutionized the approach to the systemic treatment of cancer. The programmed death 1 (PD-1) inhibitory checkpoint, in particular, has played a key role in understanding how certain cancers can evade immune surveillance. Blocking the interaction between the PD-1 receptor and its primary ligand (PD-L1) has demonstrated remarkable anti-cancer activity, and has led to the recent accelerated approval of two anti-PD-1 drugs for use in unresectable and metastatic melanoma in the USA. Results of these therapeutic advances have solidified the role of immunotherapy in the treatment of melanoma, results that may be applicable to the treatment of other cancers. In this review, we discuss the role of the PD-1 pathway in the immune system and the anti-cancer mechanism of action of inhibiting the PD-1/PD-L1 interaction. We also review the efficacy and safety data of currently approved and in-development anti-PD-1 agents, and explore the next steps to further improve patient outcomes.

12 Review PD-1 and PD-L1 antibodies for melanoma. 2014

Tsai, Katy K / Zarzoso, Inés / Daud, Adil I. ·a University of California San Francisco ; San Francisco , CA USA. ·Hum Vaccin Immunother · Pubmed #25625924.

ABSTRACT: Melanoma is the most serious form of skin cancer. Metastatic melanoma historically carries a poor prognosis and until recently there have been few effective agents available to treat widely disseminated disease. Recognition of the immunogenic nature of melanoma has resulted in the development of various immunotherapeutic approaches, especially with regards to the programmed cell death 1 (PD-1) receptor and its ligand (PD-L1). Antibodies targeting the PD-1 axis have shown enormous potential in the treatment of metastatic melanoma. Here, we will review the immune basis for the disease and discuss approved immunotherapeutic options for advanced melanoma, as well as the current state of development of PD-1 and PD-L1 antibodies and their importance in shaping the future of melanoma treatment.

13 Review Combinatorial approach to treatment of melanoma. 2014

Ashworth, Michelle T / Daud, Adil I. ·Hematology/Oncology, University of California, San Francisco, 505 Parnassus Avenue, M1286 MS1270, San Francisco, CA 94143, USA. · Melanoma Clinical Research, UCSF Helen Diller Family Comprehensive Cancer Center, 1600 Divisadero Street, San Francisco, CA 94115, USA. Electronic address: adaud@medicine.ucsf.edu. ·Hematol Oncol Clin North Am · Pubmed #24880950.

ABSTRACT: There are multiple effective and well-tolerated systemic therapy treatments for the treatment of advanced melanoma, as well as new immunotherapy and targeted therapy agents in clinical trials. Traditional cytotoxic chemotherapy and targeted BRAF inhibitors can increase antigen presentation and can rebalance the intratumoral immune milieu. The combination of pulsed cytotoxic therapy and immunotherapy is a logical next step in designing treatment regimens. Combination radiotherapy and immunotherapy also has experimental and clinical support. The standard of care for patients with advanced melanoma remains participation in clinical trials in order to enhance understanding of the effectiveness and toxicities of combination regimens.

14 Review Melanoma immunotherapy. 2014

Sanlorenzo, Martina / Vujic, Igor / Posch, Christian / Dajee, Akshay / Yen, Adam / Kim, Sarasa / Ashworth, Michelle / Rosenblum, Michael D / Algazi, Alain / Osella-Abate, Simona / Quaglino, Pietro / Daud, Adil / Ortiz-Urda, Susanna. ·University of California San Francisco; San Francisco, CA USA; Department of Medical Sciences; Section of Dermatology; University of Turin; Turin, Italy. · University of California San Francisco; San Francisco, CA USA; The Rudolfstiftung Hospital; Vienna, Austria. · University of California San Francisco; San Francisco, CA USA. · Department of Medical Sciences; Section of Dermatology; University of Turin; Turin, Italy. ·Cancer Biol Ther · Pubmed #24651672.

ABSTRACT: Immunotherapy is a cornerstone in the treatment of melanoma, and is intended to modulate the host immunity against the tumor. Immunotherapy can be used in an adjuvant setting, after complete surgical excision in patients with a high risk of disease relapse and as a treatment in advanced (unresectable or metastatic) stages. Development of novel therapeutic approaches and the optimization of existing therapies hold a great promise in the field of melanoma therapy research. Different clinical trials are ongoing, and immunotherapy is showing the ability to confirm durable clinical benefits in selected groups of melanoma patients. The aim of this review is to summarize different types of immunotherapy agents, as well as to discuss different strategies, complementary regimens, and possible biomarkers of response to the treatment.

15 Review Plasmid IL-12 electroporation in melanoma. 2012

Cha, Edward / Daud, Adil. ·Department of Medicine; University of California-San Francisco, CA, USA. Edward.cha@ucsf.edu ·Hum Vaccin Immunother · Pubmed #23151447.

ABSTRACT: Intratumoral gene electroporation uses electric charges to facilitate entry of plasmid DNA into cells in a reproducible and highly efficient manner, especially to accessible sites such as cutaneous and subcutaneous melanomas. Effective for locally treated disease, electroporation of plasmid DNA encoding interleukin-12 can also induce responses in untreated distant disease, suggesting that adaptive immune responses are being elicited that can target melanoma-associated antigens. In vivo electroporation with immunomodulatory cytokine DNA is a promising approach that can trigger systemic anti-tumor immune responses without the systemic toxicity associated with intravenous cytokine delivery and potentially offer complete long-term tumor regression.

16 Review Management of pegylated interferon alpha toxicity in adjuvant therapy of melanoma. 2012

Daud, Adil / Soon, Christopher / Dummer, Reinhard / Eggermont, Alexander M M / Hwu, Wen-Jen / Grob, Jean Jacques / Garbe, Claus / Hauschild, Axel. ·University of California, San Francisco, Melanoma Program, San Francisco 1600 Divisadero St, Rm A741, Box 1770, San Francisco, CA 94115, USA. adaud@medicine.ucsf.edu ·Expert Opin Biol Ther · Pubmed #22694288.

ABSTRACT: INTRODUCTION: Both native IFNα2b and pegylated IFNα2b (PegIFNα2b) are approved for the adjuvant treatment of high-risk melanoma. AREAS COVERED: This review compares the toxicity profiles of high-dose IFNα2b (HDI) and PegIFNα2b, and provides recommendations on the management of common PegIFNα2b-related toxicities, based on available clinical data and published literature. EXPERT OPINION: The toxicity profile of PegIFNα2b at the approved dose (6 μg/kg/week for 8 weeks then 3 μg/kg/week for up to 5 years) is qualitatively similar to HDI in melanoma. The most common adverse events (AEs) are fatigue, anorexia, hepatotoxicity, flu-like symptoms, injection site reactions and depression. However, fatigue and flu-like symptoms appear less severe with PegIFNα2b, and toxicity seems to occur earlier, whereas with HDI toxicity may increase with time. Most AEs can be managed effectively by dose modification and aggressive symptom control. Dosing to tolerance using a three-step dose reduction schedule to maintain an ECOG performance status of 0 - 1 may enable patients experiencing toxicity to remain on treatment; this can be applied readily in clinical practice. PegIFNα2b is therefore a valuable alternative option for adjuvant treatment in melanoma, with a toxicity profile similar to that of HDI overall but a more convenient administration schedule.

17 Review Cutting edge in medical management of cutaneous oncology. 2012

Chong, Kim / Daud, Adil / Ortiz-Urda, Susana / Arron, Sarah T / Anonymous1980727. ·Department of Dermatology, University of California at San Francisco, San Francisco, CA 94143, USA. arrons@derm.ucsf.edu ·Semin Cutan Med Surg · Pubmed #22640435.

ABSTRACT: Traditional chemotherapy has resulted in only a modest response, if any, for the 3 most common cutaneous malignancies of basal cell carcinoma, squamous cell carcinoma, and melanoma. Recent advances in understanding of the defects in the pathways driving tumorigenesis have changed the way that we think of these cancers and paved the way to targeted therapy for specific tumors. In this review, we will introduce the novel systemic treatments currently available for these cancers in the context of what is understood about the tumor pathogenesis. We will also introduce ongoing studies that will hopefully broaden our options for highly effective and tolerable treatment.

18 Review Beyond BRAF in melanoma. 2012

Daud, Adil / Bastian, Boris C. ·University of California, San Francisco, CA 94143, USA. ·Curr Top Microbiol Immunol · Pubmed #21826607.

ABSTRACT: Recent progress in the analysis of genetic alterations in melanoma has identified recurrent mutations that result in the activation of critical signaling pathways promoting growth and survival of tumors cells. Alterations in the RAS-RAF-MAP kinase and PI3-kinase signaling pathways are commonly altered in melanoma. Mutations in BRAF, NRAS, KIT, and GNAQ occur in a mutually exclusive pattern and lead to MAP-kinase activation. Loss of PTEN function, primarily by deletion, is the most common known genetic alteration in the PI3-kinase cascade, and is commonly associated with BRAF mutations (Curtin et al., N Engl J Med 353:2135-2147, 2005; Tsao et al., Cancer Res 60:1800-1804, 2000, J Investig Dermatol 122:337-341, 2004). The growth advantage conveyed by the constitutive activation of these pathways leads to positive selection of cells that have acquired the mutations and in many instances leads to critical dependency of the cancer cells on their activation. This creates opportunities for therapeutic interventions targeted at signaling components within these pathways that are amenable for pharmacological inhibition. This concept follows the paradigm established by the landmark discovery that inhibition of the fusion kinase BCR-ABL can be used to treat chronic myelogenous leukemia (Druker et al., N Engl J Med 344:1031-037, 2001). The review will focus primarily on kinases involved in signaling that are currently being evaluated for therapeutic intervention in melanoma.

19 Review Preclinical and clinical activity of the topoisomerase I inhibitor, karenitecin, in melanoma. 2011

Munster, Pamela N / Daud, Adil I. ·University of California, Department of Medicine, San Francisco, CA , USA. Pmunster@medicine.ucsf.edu ·Expert Opin Investig Drugs · Pubmed #21985236.

ABSTRACT: INTRODUCTION: This review covers the preclinical and clinical activity of the novel camptothecin analog, karenitecin, in melanoma. AREAS COVERED: While the camptothecins are widely used antitumor agents that inhibit topoisomerase I, their utility is limited by instability, high interpatient variability and the development of drug resistance. Karenitecin was rationally designed to overcome these limitations. The authors review the data on karenitecin in preclinical models and in clinical trials in melanoma using studies published in Medline and reports presented at AACR and ASCO. EXPERT OPINION: Karenitecin shows activity in melanoma, both as a single agent and in combination. In adverse prognostic factor melanoma, karenitecin showed prolonged disease stabilization in 34% of patients. Because preclinical studies suggested a synergistic interaction between karenitecin and HDAC inhibitors, a schedule-specific combination Phase I-II trial of valproic acid and karenitecin was carried out in heavily pretreated melanoma patients which showed a benefit rate in 47% patients with acceptable toxicity. The treatment for melanoma is in rapid transition and genomic profiling is now an integral part, and hence the optimal use of karenitecin in melanoma should be re-evaluated with regard to specific mutational status.

20 Review Cutaneous melanoma: a model to study cancer metastasis. 2011

Leong, Stanley P L / Gershenwald, Jeffrey E / Soong, Seng-Jaw / Schadendorf, Dirk / Tarhini, Ahmad A / Agarwala, Sanjiv / Hauschild, Axel / Soon, Christopher W M / Daud, Adil / Kashani-Sabet, Mohammed. ·Center for Melanoma Research and Treatment and Department of Surgery, California Pacific Medical Center and Research Institute, San Francisco, California 94115, USA. leongsx@cpmcri.org ·J Surg Oncol · Pubmed #21480247.

ABSTRACT: Nodal status in melanoma is a critically important prognostic factor for patient outcome. The survival rate drops to <10% when melanoma has spread beyond the regional lymph nodes and includes visceral involvement. In general, the process of melanoma metastasis is progressive in that dissemination of melanoma from the primary site to the regional lymph nodes occurs prior to systemic disease. The goal of this review article is to describe melanoma as a clinical model to study cancer metastasis. A future challenge is to develop a molecular taxonomy to subgroup melanoma patients at various stages of tumor progression for more accurate targeted treatment.

21 Review State of the science 60th anniversary review: 60 Years of advances in cutaneous melanoma epidemiology, diagnosis, and treatment, as reported in the journal Cancer. 2008

Demierre, Marie-France / Sabel, Michael S / Margolin, Kim A / Daud, Adil I / Sondak, Vernon K. ·Department of Dermatology, Boston University School of Medicine, Boston, Massachusetts, USA. ·Cancer · Pubmed #18798543.

ABSTRACT: -- No abstract --

22 Clinical Trial Outcomes by line of therapy and programmed death ligand 1 expression in patients with advanced melanoma treated with pembrolizumab or ipilimumab in KEYNOTE-006: A randomised clinical trial. 2018

Carlino, Matteo S / Long, Georgina V / Schadendorf, Dirk / Robert, Caroline / Ribas, Antoni / Richtig, Erika / Nyakas, Marta / Caglevic, Christian / Tarhini, Ahmed / Blank, Christian / Hoeller, Christoph / Bar-Sela, Gil / Barrow, Catherine / Wolter, Pascal / Zhou, Honghong / Emancipator, Kenneth / Jensen, Erin H / Ebbinghaus, Scot / Ibrahim, Nageatte / Daud, Adil. ·Crown Princess Mary Cancer Centre, Westmead Hospital, Sydney, NSW, Australia; Blacktown Hospital, Blacktown, NSW, Australia; Melanoma Institute Australia, Sydney, NSW, Australia; School of Medicine, University of Sydney, Sydney, NSW, Australia. Electronic address: Matteo.carlino@sydney.edu.au. · Melanoma Institute Australia, Sydney, NSW, Australia; Department of Medical Oncology and Translational Research, University of Sydney, Sydney, NSW, Australia; Royal North Shore Hospital, Sydney, NSW, Australia; Mater Hospital, Sydney, NSW, Australia. Electronic address: georgina.long@sydney.edu.au. · Department of Dermatology, University Hospital Essen, Essen, Germany; German Cancer Consortium, Heidelberg, Germany. Electronic address: Dirk.Schadendorf@uk-essen.de. · Department of Oncology, Gustave Roussy, Villejuif, France; Paris-Sud University, Orsay, France. Electronic address: Caroline.Robert@igr.fr. · Department of Medicine, University of California, Los Angeles, Los Angeles, CA, USA. Electronic address: aribas@mednet.ucla.edu. · Department of Dermatology, Medical University of Graz, Graz, Austria. Electronic address: erika.richtig@medunigraz.at. · Department of Clinical Cancer Research, Oslo University Hospital, Oslo, Norway. Electronic address: marnya@ous-hf.no. · Unit of Investigational Cancer Drugs, Instituto Oncologico Fundación Arturo López Pérez, Santiago, Chile. Electronic address: oncodemia@yahoo.com. · Division of Hematology/Oncology, University of Pittsburgh, Pittsburgh, PA, USA. Electronic address: tarhiniaa@upmc.edu. · Division of Immunology, Netherlands Cancer Institute, Amsterdam, Netherlands. Electronic address: c.blank@nki.nl. · Department of Dermatology, Medical University of Vienna, Vienna, Austria. Electronic address: christoph.hoeller@meduniwien.ac.at. · Division of Oncology, Rambam Health Care Campus, Haifa, Israel. Electronic address: g_barsela@rambam.health.gov.il. · Wellington Blood and Cancer Centre, Wellington Hospital, Wellington, New Zealand. Electronic address: Catherine.Barrow@ccdhb.org.nz. · Leuven Cancer Institute, University Hospitals Leuven, Leuven, Belgium. Electronic address: pascalwolter@hotmail.com. · Department of BARDS, Merck & Co., Inc., Kenilworth, NJ, USA. Electronic address: honghongz@gmail.com. · Companion Diagnostics, Merck & Co., Inc., Kenilworth, NJ, USA. Electronic address: kenneth.emancipator@merck.com. · LDS - Medical Communications, Merck & Co., Inc., North Wales, PA, USA. Electronic address: erin_jensen2@merck.com. · Department of Clinical Oncology, Merck & Co., Inc., North Wales, PA, USA. Electronic address: scot_ebbinghaus@merck.com. · Department of Clinical Oncology, Merck & Co., Inc., North Wales, PA, USA. Electronic address: nageatte.ibrahim@merck.com. · University of California, San Francisco, San Francisco, CA, USA. Electronic address: adaud@medicine.ucsf.edu. ·Eur J Cancer · Pubmed #30096704.

ABSTRACT: BACKGROUND: Predictive biomarkers of patients likely to benefit from anti-programmed death 1 inhibitor therapy have clinical relevance. We examined whether line of therapy or tumour programmed death ligand 1 (PD-L1) expression affects the efficacy and safety of pembrolizumab, compared with ipilimumab, in advanced melanoma. METHODS: Of 834 patients enrolled in the randomised, open-label phase III KEYNOTE-006 study, 833 were included in this analysis. Patients were randomly assigned 1:1:1 to receive pembrolizumab 10 mg/kg every 2 or 3 weeks (for 24 months) or ipilimumab 3 mg/kg every 3 weeks (for four doses) until disease progression/intolerable toxicity. This analysis evaluated progression-free survival (PFS), overall survival (OS) and objective response rate (ORR). Data cut-off: 03 November 2016. RESULTS: Of the patients, 60.3% were male, 65.9% were treatment naive and 80.6% had PD-L1-positive tumours (median follow-up was 33.9 months). Twenty-four-month survival rates were higher with pembrolizumab than with ipilimumab in treatment-naive (PFS 31.0% versus 14.6%; OS 58.0% versus 44.7%) and previously treated patients (PFS 25.7% versus 11.3%; OS 49.2% versus 37.9%). Twenty-four-month survival rates were higher with pembrolizumab than with ipilimumab in patients with PD-L1-positive tumours (PFS 33.2% versus 13.1%; OS 58.4% versus 45.0%) and similar in PD-L1-negative tumours (PFS 14.9% versus NR [no data at 24 months for a PFS estimate]; OS 43.6% versus 31.8%). Safety of pembrolizumab by subgroup was consistent with previous reports. CONCLUSIONS: Findings support pembrolizumab monotherapy as standard of care in patients with advanced melanoma, regardless of first- or second-line therapy or PD-L1 status. CLINICALTRIALS. GOV IDENTIFIER: NCT01866319.

23 Clinical Trial Dual MEK/AKT inhibition with trametinib and GSK2141795 does not yield clinical benefit in metastatic NRAS-mutant and wild-type melanoma. 2018

Algazi, Alain P / Esteve-Puig, Rosaura / Nosrati, Adi / Hinds, Brian / Hobbs-Muthukumar, Adele / Nandoskar, Prachi / Ortiz-Urda, Susana / Chapman, Paul B / Daud, Adil. ·UCSF Melanoma Oncology, San Francisco, CA, USA. · UCSF Dermatology, San Francisco, CA, USA. · UCSD Dermatopathology, La Jolla, CA, USA. · Memorial Sloan Kettering Cancer Center, New York, NY, USA. ·Pigment Cell Melanoma Res · Pubmed #28921907.

ABSTRACT: Aberrant MAPK and PI3K pathway signaling may drive the malignant phenotype in NRAS-mutant and BRAF

24 Clinical Trial Efficacy and Safety of Pembrolizumab in Patients Enrolled in KEYNOTE-030 in the United States: An Expanded Access Program. 2017

Gangadhar, Tara C / Hwu, Wen-Jen / Postow, Michael A / Hamid, Omid / Daud, Adil / Dronca, Roxana / Joseph, Richard / O'Day, Steven J / Hodi, F S / Pavlick, Anna C / Kluger, Harriet / Oxborough, Romina P / Yang, Aiming / Gazdoiu, Mihaela / Kush, Debra A / Ebbinghaus, Scot / Salama, April K S. ·*Abramson Cancer Center of the University of Pennsylvania, Philadelphia, PA †The University of Texas MD Anderson Cancer Center, Houston, TX ‡Memorial Sloan Kettering Cancer Center §Weill Cornell Medical College §§NYU Clinical Cancer Center, New York, NY ∥The Angeles Clinic and Research Institute, Los Angeles ¶Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco ††The John Wayne Cancer Institute, Providence Saint John's Health Center, Santa Monica, CA #Mayo Clinic, Rochester, MN **Mayo Clinic, Jacksonville, FL ‡‡Dana-Farber Cancer Institute, Boston, MA ∥∥Yale Cancer Center, New Haven, CT ¶¶Clinigen, Weybridge, UK ##Merck & Co. Inc., Kenilworth, NJ ***Duke Cancer Institute, Durham, NC. ·J Immunother · Pubmed #29028788.

ABSTRACT: KEYNOTE-030 (ClinicalTrials.gov ID, NCT02083484) was a global expanded access program that allowed access to pembrolizumab, an antiprogrammed death 1 antibody, for patients with advanced melanoma before its regulatory approval. Patients with unresectable stage III/IV melanoma that progressed after standard-of-care therapy, including ipilimumab and, if BRAF mutant, a BRAF inhibitor, were eligible to receive pembrolizumab 2 mg/kg every 3 weeks. Response was assessed by immune-related response criteria by investigator review. Adverse events (AEs) were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0. In the United States, 979 patients enrolled between April and September 2014. Of the 947 evaluable patients, 621 (65.6%) remained on treatment and transitioned to receive commercial pembrolizumab following approval by the Food and Drug Administration, whereas 326 (34.4%) discontinued, most commonly for disease progression (39.6%) or death (26.4%). Objective response rate was 14.5% (95% confidence interval, 12.2%-16.8%) in the treated population (n=947) and 22.1% (95% confidence interval, 18.8%-25.5%) in patients who had ≥1 response assessment reported (n=619). Twelve patients achieved complete response. One hundred eighty-one (19.1%) patients experienced ≥1 treatment-related AE, most commonly general disorders (8.0%), skin/subcutaneous tissue disorders (7.3%), and gastrointestinal disorders (6.4%); 29 (3.1%) patients experienced ≥1 grade 3/4 treatment-related AE. Immune-mediated AEs were also reported. There were no treatment-related deaths. The safety and efficacy observed in this expanded access program were consistent with those previously reported for similar populations and support the use of pembrolizumab for patients with advanced melanoma.

25 Clinical Trial Final analysis of a randomised trial comparing pembrolizumab versus investigator-choice chemotherapy for ipilimumab-refractory advanced melanoma. 2017

Hamid, Omid / Puzanov, Igor / Dummer, Reinhard / Schachter, Jacob / Daud, Adil / Schadendorf, Dirk / Blank, Christian / Cranmer, Lee D / Robert, Caroline / Pavlick, Anna C / Gonzalez, Rene / Hodi, F Stephen / Ascierto, Paolo A / Salama, April K S / Margolin, Kim A / Gangadhar, Tara C / Wei, Ziwen / Ebbinghaus, Scot / Ibrahim, Nageatte / Ribas, Antoni. ·The Angeles Clinic and Research Institute, Los Angeles, CA, USA. Electronic address: ohamid@theangelesclinic.org. · Vanderbilt-Ingram Cancer Center, Nashville, TN, USA. · University of Zürich, Zürich, Switzerland. · Ella Lemelbaum Institute of Melanoma, Sheba Medical Center, Tel Hashomer, Israel. · University of California, San Francisco, San Francisco, CA, USA. · University Hospital Essen, Essen, Germany. · Netherlands Cancer Institute, Amsterdam, The Netherlands. · University of Arizona Cancer Center, Tucson, AZ, USA. · Gustave Roussy and Paris-Sud University, Villejuif, France. · New York University Cancer Institute, New York, NY, USA. · University of Colorado Denver, Aurora, CO, USA. · Dana-Farber Cancer Institute, Boston, MA, USA. · Istituto Nazionale Tumori Fondazione G. Pascale, Napoli, Italy. · Duke Cancer Institute, Durham, NC, USA. · City of Hope, Duarte, CA, USA. · Abramson Cancer Center of the University of Pennsylvania, Philadelphia, PA, USA. · Merck & Co., Inc., Kenilworth, NJ, USA. · University of California Los Angeles, Los Angeles, CA, USA. ·Eur J Cancer · Pubmed #28961465.

ABSTRACT: AIM: To evaluate the protocol-specified final analysis of overall survival (OS) in the KEYNOTE-002 study (NCT01704287) of pembrolizumab versus chemotherapy in patients with ipilimumab-refractory, advanced melanoma. METHODS: In this randomised, phase II study, eligible patients had advanced melanoma with documented progression after two or more ipilimumab doses, previous BRAF or MEK inhibitor or both, if BRAF RESULTS: A total of 180 patients were randomised to pembrolizumab 2 mg/kg, 181 to pembrolizumab 10 mg/kg and 179 to chemotherapy. At a median follow-up of 28 months (range 24.1-35.5), 368 patients died and 98 (55%) crossed over to pembrolizumab. Pembrolizumab 2 mg/kg (hazard ratio [HR] 0.86, 95% confidence interval [CI] 0.67-1.10, p = 0.117) and 10 mg/kg (0.74, 0.57-0.96, p = 0.011) resulted in a non-statistically significant improvement in OS versus chemotherapy; median OS was 13.4 (95% CI 11.0-16.4) and 14.7 (95% CI 11.3-19.5), respectively, versus 11.0 months (95% CI 8.9-13.8), with limited improvement after censoring for crossover. Two-year survival rates were 36% and 38%, versus 30%. Progression-free survival, objective response rate and duration of response improved with pembrolizumab versus chemotherapy, regardless of dose. Grade III-V treatment-related adverse events occurred in 24 (13.5%), 30 (16.8%) and 45 (26.3%) patients, respectively. CONCLUSION: Improvement in OS with pembrolizumab was not statistically significant at either dose versus chemotherapy.

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