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Melanoma: HELP
Articles by Nikhil I. Khushalani
Based on 30 articles published since 2010
(Why 30 articles?)
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Between 2010 and 2020, N. Khushalani wrote the following 30 articles about Melanoma.
 
+ Citations + Abstracts
Pages: 1 · 2
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 / Anonymous5190793. ·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 / Anonymous4400755. ·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 Review Leptomeningeal disease in melanoma patients: An update to treatment, challenges, and future directions. 2020

Glitza, Isabella C / Smalley, Keiran S M / Brastianos, Priscilla K / Davies, Michael A / McCutcheon, Ian / Liu, James K C / Ahmed, Kamran A / Arrington, John A / Evernden, Brittany R / Smalley, Inna / Eroglu, Zeynep / Khushalani, Nikhil / Margolin, Kim / Kluger, Harriet / Atkins, Michael B / Tawbi, Hussein / Boire, Adrienne / Forsyth, Peter. ·Department of Melanoma Medical Oncology, UT MD Anderson Cancer Center, Houston, TX, USA. · Melanoma Research Center of Excellence, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA. · Department of Hematology/Oncology, Massachusetts General Hospital, Boston, MA. · Department of Neurosurgery, UT MD Anderson Cancer Center, Houston, TX, USA. · Department of Neuro-Oncology & Tumor Biology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA. · Department of Radiation Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA. · Head of Neuroradiology Section, Department of Radiology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA. · Department of Tumor Biology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA. · Department of Cutaneous Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA. · Department of Medical Oncology and Therapeutics Research, City of Hope National Medical Center, Duarte, CA, USA. · Department of Medical Oncology, Yale Cancer Center, New Haven, CT, USA. · Department of Medical Oncology, Georgetown University Medical Center, Washington, DC, USA. · Department of Neuro-Oncology, Memorial Sloan Kettering, New York, NY, USA. ·Pigment Cell Melanoma Res · Pubmed #31916400.

ABSTRACT: In February 2018, the Melanoma Research Foundation and the Moffitt Cancer Center hosted the Second Summit on Melanoma Central Nervous System Metastases in Tampa, Florida. The meeting included investigators from multiple academic centers and disciplines. A consensus summary of the progress and challenges in melanoma parenchymal brain metastases was published (Eroglu et al., Pigment Cell & Melanoma Research, 2019, 32, 458). Here, we will describe the current state of basic, translational, clinical research, and therapeutic management, for melanoma patients with leptomeningeal disease. We also outline key challenges and barriers to be overcome to make progress in this deadly disease.

5 Review Principles of Targeted Therapy for Melanoma. 2020

Sun, James / Carr, Michael J / Khushalani, Nikhil I. ·Department of Cutaneous Oncology, Moffitt Cancer Center, 10920 North McKinley Drive, 4th Floor, Tampa, FL 33612, USA. · Department of Cutaneous Oncology, Moffitt Cancer Center, 10920 North McKinley Drive, 4th Floor, Tampa, FL 33612, USA. Electronic address: nikhil.khushalani@moffitt.org. ·Surg Clin North Am · Pubmed #31753111.

ABSTRACT: Targeted BRAF and MEK inhibition has become an appropriate first-line treatment of BRAF-mutant advanced cutaneous melanoma. The authors present an overview of the MAPK pathway as well as the other major pathways implicated in melanoma development. Melanoma brain metastases are a devastating complication of melanoma that can be traced to derangements in cell signaling pathways, and the current evidence for targeted therapy is reviewed. Finally, activating KIT mutations are rarely found to cause melanomas and may provide an actionable target for therapy. The authors review the current evidence for targeted KIT therapy and summarize the ongoing clinical trials.

6 Review Current Immunotherapy Practices in Melanoma. 2019

Rothermel, Luke D / Sarnaik, Amod A / Khushalani, Nikhil I / Sondak, Vernon K. ·Moffitt Cancer Center, 12902 USF Magnolia Drive, Tampa, FL 33612, USA. · Department of Cutaneous Oncology, Moffitt Cancer Center, 10920 N. McKinley Drive, Tampa, FL 33612, USA. · Department of Cutaneous Oncology, Moffitt Cancer Center, 10920 N. McKinley Drive, Tampa, FL 33612, USA. Electronic address: Vernon.sondak@moffitt.org. ·Surg Oncol Clin N Am · Pubmed #31079796.

ABSTRACT: Immunotherapy has revolutionized the treatment of melanoma, with implications for the surgical management of this disease. Surgeons must be aware of the impact of various immunotherapies on patients with resectable and unresectable disease, and how surgical decision-making should progress as a result. We expect that current and developing immunotherapies will increase surgeon involvement for resection of metastatic melanoma, whether for tumor harvests to generate autologous lymphocytes or for consolidating control of disease beyond what immunotherapies alone can achieve. Despite remarkable advancements in the field, significant work is needed to optimize the immuno-modulation that targets cancers while minimizing toxicity for patients.

7 Review Intralesional and systemic immunotherapy for metastatic melanoma. 2016

Luu, Carrie / Khushalani, Nikhil I / Zager, Jonathan S. ·a Department of Cutaneous Oncology , H. Lee Moffitt Cancer Center , Tampa , FL , USA. · b Department of Cutaneous Oncology , Director of Regional Therapies Moffitt Cancer Center , Tampa , FL , USA. ·Expert Opin Biol Ther · Pubmed #27602429.

ABSTRACT: INTRODUCTION: Immunotherapy has revolutionized the treatment of metastatic melanoma and dramatically improved patient outcomes. Ipilimumab, an inhibitor of cytotoxic T-lymphocyte antigen-4 (CTLA-4), was the first immunotherapeutic agent to demonstrate improved survival in advanced melanoma. More recently, other immune checkpoint inhibitors, including the programmed death-1 (PD-1) inhibitors pembrolizumab and nivolumab, have demonstrated efficacy in locally advanced unresectable and metastatic melanoma. In addition to systemically delivered immunotherapies, intralesional therapies such as talimogene laherparepvec (TVEC) play an important role in the treatment of locoregionally advanced and metastatic melanoma. Areas covered: This review provides an overview of the mechanisms behind immune checkpoint inhibitors. Clinical evidence of their efficacy is presented and discussion of new patterns of response and associated immune related adverse events associated with immunotherapy are provided. Expert opinion: Treatment options for locally advanced and metastatic melanoma are expanding with new developments in immunotherapy and immune checkpoint inhibitors. The utility of these novel therapies in the adjuvant setting is currently being explored. The ideal treatment of metastatic melanoma continues to be multimodal, combining systemic treatments, intralesional and regional therapies, surgery and radiotherapy to achieve optimal outcomes.

8 Review BRAF and beyond: Tailoring strategies for the individual melanoma patient. 2014

Jarkowski, Anthony / Khushalani, Nikhil I. ·Department of Pharmacy, James P. Wilmot Cancer Center, University of Rochester Medical Center, Rochester, USA. · Department of Medicine, Roswell Park Cancer Institute, Buffalo, NY, USA. ·J Carcinog · Pubmed #24737949.

ABSTRACT: Until recently, options for therapy in metastatic melanoma were limited. The understanding of immune check-point blockade and the discovery of molecular pathways involving driver mutations like BRAF has transformed the therapeutic landscape in this disease. Ipilimumab was the first drug shown to improve survival while vemurafenib demonstrated rapid responses never seen before in melanoma. Drugs from these classes and others are now in advanced stages of development and primed to positively impact patient survival in an incremental fashion. In this review, we highlight some of the developments during this renaissance in melanoma therapy and discuss agents of promise. Clinical challenges we face include individualizing therapy for patients, overcoming resistance to molecularly targeted therapy and developing rationale combinations or sequences of drugs. A concerted bench and bedside effort in this direction will undoubtedly keep melanoma in the forefront in an era of personalized medicine.

9 Clinical Trial NCI 8628: A randomized phase 2 study of ziv-aflibercept and high-dose interleukin 2 or high-dose interleukin 2 alone for inoperable stage III or IV melanoma. 2018

Tarhini, Ahmad A / Frankel, Paul / Ruel, Christopher / Ernstoff, Marc S / Kuzel, Timothy M / Logan, Theodore F / Khushalani, Nikhil I / Tawbi, Hussein A / Margolin, Kim A / Awasthi, Sanjay / Butterfield, Lisa H / McDermott, David / Chen, Alice / Lara, Primo N / Kirkwood, John M. ·University of Pittsburgh Medical Center Hillman Cancer Center, University of Pittsburgh, Pittsburgh, Pennsylvania. · Department of Hematology and Oncology, Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center, Cleveland, Ohio. · City of Hope National Medical Center, Duarte, California. · Roswell Park Comprehensive Cancer Center, Buffalo, New York. · Rush University Medical Center, Chicago, Illinois. · Indiana University Melvin and Bren Simon Cancer Center, Indianapolis, Indiana. · Moffitt Cancer Center, Tampa, Florida. · The University of Texas MD Anderson Cancer Center, Houston, Texas. · Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania. · Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania. · Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania. · Beth Israel Deaconess Medical Center, Boston, Massachusetts. · Cancer Therapy Evaluation Program, National Cancer Institute, Bethesda, Maryland. · University of California at Davis Comprehensive Cancer Center, Sacramento, California. ·Cancer · Pubmed #30303516.

ABSTRACT: BACKGROUND: Interleukin 2 (IL-2) is a growth factor for T and natural killer cells, promotes proinflammatory cytokines, and can lead to durable responses in patients with melanoma. Vascular endothelial growth factor (VEGF) promotes angiogenesis and modulates host innate and adaptive immunity. High VEGF levels were found to be associated with nonresponse to IL-2. Ziv-aflibercept may deplete VEGF and thereby enhance antitumor T-cell responses, thus supporting a combination immunotherapeutic strategy with IL-2. METHODS: NCI 8628 was a phase 2 trial of ziv-aflibercept and IL-2 (arm A) versus IL-2 alone (arm B) randomized at 2:1, respectively. Eligible patients had inoperable American Joint Committee on Cancer stage III or stage IV melanoma. The primary endpoint was progression-free survival (PFS). RESULTS: A total of 89 patients were enrolled and 84 patients were treated. The median follow-up was 41.4 months. Among treated patients (55 patients in arm A and 29 patients in arm B), PFS was significantly improved in favor of arm A, with a median of 6.9 months (95% confidence interval [95% CI], 4.1-8.7 months) versus 2.3 months (95% CI, 1.6-3.5 months) (P<.001). No significant difference was noted with regard to overall survival, with a median of 26.9 months (95% CI, 14.4-63.6 months) for arm A and 24.2 months (95% CI, 11.3-36.4 months) for arm B. The response rate (according to Response Evaluation Criteria In Solid Tumors [RECIST]) was 22% in arm A (4 complete responses [CRs] and 8 partial responses [PRs]) and 17% in arm B (1 CR and 4 PRs). Stable disease or PR or CR was noted in 65% of patients in arm A and 48% of patients in arm B. The combination was found to be superior to monotherapy in patients with high and low levels of serum VEGF and VEGF receptor 2. Adverse events were consistent with the expected profiles of monotherapy with IL-2 and ziv-aflibercept. CONCLUSIONS: Ziv-aflibercept and IL-2 were found to significantly improve PFS compared with IL-2 alone, thereby meeting the primary endpoint of the current study. These findings support further study of immunotherapeutic combination strategies involving VEGF inhibitors.

10 Clinical Trial Combined Nivolumab and Ipilimumab in Melanoma Metastatic to the Brain. 2018

Tawbi, Hussein A / Forsyth, Peter A / Algazi, Alain / Hamid, Omid / Hodi, F Stephen / Moschos, Stergios J / Khushalani, Nikhil I / Lewis, Karl / Lao, Christopher D / Postow, Michael A / Atkins, Michael B / Ernstoff, Marc S / Reardon, David A / Puzanov, Igor / Kudchadkar, Ragini R / Thomas, Reena P / Tarhini, Ahmad / Pavlick, Anna C / Jiang, Joel / Avila, Alexandre / Demelo, Sheena / Margolin, Kim. ·From the University of Texas M.D. Anderson Cancer Center, Houston (H.A.T.) · Moffitt Cancer Center and Research Institute, Tampa, FL (P.A.F., N.I.K.) · University of California-San Francisco, San Francisco (A. Algazi), the Angeles Clinic and Research Institute, Los Angeles (O.H.), Stanford University Hospital, Palo Alto (R.P.T.), and the Department of Medical Oncology, City of Hope, Duarte (K.M.) - all in California · Dana-Farber Cancer Institute, Boston (F.S.H., D.A.R.) · University of North Carolina Lineberger Comprehensive Cancer Center, Chapel Hill (S.J.M.) · University of Colorado Comprehensive Cancer Center, Aurora (K.L.) · University of Michigan, Ann Arbor (C.D.L.) · Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York (M.A.P.), Roswell Park Cancer Institute, Buffalo (M.S.E., I.P.), and New York University, Lake Success (A.C.P.) - all in New York · Georgetown-Lombardi Comprehensive Cancer Center, Washington DC (M.B.A.) · Winship Cancer Institute of Emory University, Atlanta (R.R.K.) · University of Pittsburgh Medical Center, Pittsburgh (A.T.) · Bristol-Myers Squibb, Princeton, NJ (J.J., A. Avila, S.D.) · and Cleveland Clinic-Taussig Cancer Institute, Cleveland (A.T.). ·N Engl J Med · Pubmed #30134131.

ABSTRACT: BACKGROUND: Brain metastases are a common cause of disabling neurologic complications and death in patients with metastatic melanoma. Previous studies of nivolumab combined with ipilimumab in metastatic melanoma have excluded patients with untreated brain metastases. We evaluated the efficacy and safety of nivolumab plus ipilimumab in patients with melanoma who had untreated brain metastases. METHODS: In this open-label, multicenter, phase 2 study, patients with metastatic melanoma and at least one measurable, nonirradiated brain metastasis (tumor diameter, 0.5 to 3 cm) and no neurologic symptoms received nivolumab (1 mg per kilogram of body weight) plus ipilimumab (3 mg per kilogram) every 3 weeks for up to four doses, followed by nivolumab (3 mg per kilogram) every 2 weeks until progression or unacceptable toxic effects. The primary end point was the rate of intracranial clinical benefit, defined as the percentage of patients who had stable disease for at least 6 months, complete response, or partial response. RESULTS: Among 94 patients with a median follow-up of 14.0 months, the rate of intracranial clinical benefit was 57% (95% confidence interval [CI], 47 to 68); the rate of complete response was 26%, the rate of partial response was 30%, and the rate of stable disease for at least 6 months was 2%. The rate of extracranial clinical benefit was 56% (95% CI, 46 to 67). Treatment-related grade 3 or 4 adverse events were reported in 55% of patients, including events involving the central nervous system in 7%. One patient died from immune-related myocarditis. The safety profile of the regimen was similar to that reported in patients with melanoma who do not have brain metastases. CONCLUSIONS: Nivolumab combined with ipilimumab had clinically meaningful intracranial efficacy, concordant with extracranial activity, in patients with melanoma who had untreated brain metastases. (Funded by Bristol-Myers Squibb and the National Cancer Institute; CheckMate 204 ClinicalTrials.gov number, NCT02320058 .).

11 Clinical Trial Combined BRAF and HSP90 Inhibition in Patients with Unresectable 2018

Eroglu, Zeynep / Chen, Y Ann / Gibney, Geoffrey T / Weber, Jeffrey S / Kudchadkar, Ragini R / Khushalani, Nikhil I / Markowitz, Joseph / Brohl, Andrew S / Tetteh, Leticia F / Ramadan, Howida / Arnone, Gina / Li, Jiannong / Zhao, Xiuhua / Sharma, Ritin / Darville, Lancia N F / Fang, Bin / Smalley, Inna / Messina, Jane L / Koomen, John M / Sondak, Vernon K / Smalley, Keiran S M. ·Department of Cutaneous Oncology, Moffitt Cancer Center, Tampa, Florida. · Department of Biostatistics and Bioinformatics, Moffitt Cancer Center, Tampa, Florida. · Georgetown Lombardi Comprehensive Cancer Center, Washington, District of Columbia. · NYU Langone Medical Center, New York, New York. · Winship Cancer Institute of Emory University School of Medicine, Atlanta, Georgia. · Department of Tumor Biology, Moffitt Cancer Center, Tampa, Florida. · Department of Proteomics, Moffitt Cancer Center, Tampa, Florida. · Molecular Oncology, Moffitt Cancer Center, Tampa, Florida. · Department of Cutaneous Oncology, Moffitt Cancer Center, Tampa, Florida. keiran.smalley@moffitt.org. ·Clin Cancer Res · Pubmed #29674508.

ABSTRACT:

12 Clinical Trial Overall Survival in Patients With Advanced Melanoma Who Received Nivolumab Versus Investigator's Choice Chemotherapy in CheckMate 037: A Randomized, Controlled, Open-Label Phase III Trial. 2018

Larkin, James / Minor, David / D'Angelo, Sandra / Neyns, Bart / Smylie, Michael / Miller, Wilson H / Gutzmer, Ralf / Linette, Gerald / Chmielowski, Bartosz / Lao, Christopher D / Lorigan, Paul / Grossmann, Kenneth / Hassel, Jessica C / Sznol, Mario / Daud, Adil / Sosman, Jeffrey / Khushalani, Nikhil / Schadendorf, Dirk / Hoeller, Christoph / Walker, Dana / Kong, George / Horak, Christine / Weber, Jeffrey. ·James Larkin, Royal Marsden NHS Foundation Trust, London · Paul Lorigan, The Christie National Health Service Foundation Trust, Manchester, United Kingdom · David Minor, California Pacific Medical Center Research Institute · Adil Daud, University of California San Francisco, San Francisco · Bartosz Chmielowski, University of California, Santa Monica, CA · Sandra D'Angelo, Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College · Jeffrey Weber, Perlmutter Cancer Center at New York University-Langone Medical Center, New York · Nikhil Khushalani, Roswell Park Cancer Institute, Buffalo, NY · Gerald Linette, Washington University, St. Louis, MO · Christopher D. Lao, University of Michigan, Ann Arbor, MI · Kenneth Grossmann, Huntsman Cancer Institute, Salt Lake City, UT · Mario Sznol, Yale Comprehensive Cancer Center, New Haven, CT · Jeffrey Sosman, Northwestern University, Chicago, IL · Dana Walker, George Kong, and Christine Horak, Bristol-Myers Squibb, Princeton, NJ · Bart Neyns, University Hospital, Vrije Universiteit Brussel, Brussels, Belgium · Michael Smylie, Cross Cancer Institute, Edmonton, Alberta · Wilson H. Miller Jr, Jewish General Hospital and Segal Cancer Centre, McGill University, Montreal, Quebc, Canada · Ralf Gutzmer, Medizinische Hochschule Hannover, Hannover · Jessica C. Hassel, Nationale Centrum für Tumorerkrankungen Heidelberg, Heidelberg · Dirk Schadendorf, University Hospital Essen, Essen, Germany · and Christoph Hoeller, Medical University of Vienna, Wien, Austria. ·J Clin Oncol · Pubmed #28671856.

ABSTRACT: Purpose Until recently, limited options existed for patients with advanced melanoma who experienced disease progression while receiving treatment with ipilimumab. Here, we report the coprimary overall survival (OS) end point of CheckMate 037, which has previously shown that nivolumab resulted in more patients achieving an objective response compared with chemotherapy regimens in ipilimumab-refractory patients with advanced melanoma. Patients and Methods Patients were stratified by programmed death-ligand 1 expression, BRAF status, and best prior cytotoxic T-lymphocyte antigen-4 therapy response, then randomly assigned 2:1 to nivolumab 3 mg/kg intravenously every 2 weeks or investigator's choice chemotherapy (ICC; dacarbazine 1,000 mg/m

13 Clinical Trial Ipilimumab alone or in combination with nivolumab after progression on anti-PD-1 therapy in advanced melanoma. 2017

Zimmer, Lisa / Apuri, Susmitha / Eroglu, Zeynep / Kottschade, Lisa A / Forschner, Andrea / Gutzmer, Ralf / Schlaak, Max / Heinzerling, Lucie / Krackhardt, Angela M / Loquai, Carmen / Markovic, Svetomir N / Joseph, Richard W / Markey, Kelly / Utikal, Jochen S / Weishaupt, Carsten / Goldinger, Simone M / Sondak, Vernon K / Zager, Jonathan S / Schadendorf, Dirk / Khushalani, Nikhil I. ·Department of Dermatology, University Hospital, University Duisburg-Essen, Germany & German Cancer Consortium (DKTK), Heidelberg, Germany. Electronic address: lisa.zimmer@uk-essen.de. · Hematology/Oncology Fellowship Program, H Lee Moffitt Cancer Center and Research Institute/University of South Florida, Tampa, FL, USA. · Department of Cutaneous Oncology, Moffitt Cancer Center, Tampa, FL, USA. · Department of Oncology, Hematology and Immunology, Mayo Clinic, Rochester, MN, USA. · Department of Dermatology, University Hospital Tübingen, Germany. · Department of Dermatology and Allergy, Skin Cancer Center Hannover, Hannover Medical School, Germany. · Department of Dermatology, University Hospital Cologne, Skin Cancer Center, Center for Integrated Oncology (CIO) Köln Bonn, Germany. · Department of Dermatology, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nürnberg (FAU), Germany. · III. Medical Department, Technische Universität München (TUM) Munich, Germany. · Department of Dermatology, University Hospital Mainz, Germany. · Skin Cancer Unit, German Cancer Research Center (DKFZ), Heidelberg, Germany; Department of Dermatology, Venereology and Allergology, University Medical Center Mannheim, Ruprecht-Karl University of Heidelberg, Mannheim, Germany. · Department of Dermatology, University Hospital Münster, Germany. · Department of Dermatology, University Hospital Zurich, Switzerland. · Department of Dermatology, University Hospital, University Duisburg-Essen, Germany & German Cancer Consortium (DKTK), Heidelberg, Germany. ·Eur J Cancer · Pubmed #28214657.

ABSTRACT: BACKGROUND: The anti-programmed cell death-1 (PD-1) inhibitors pembrolizumab and nivolumab alone or in combination with ipilimumab have shown improved objective response rates and progression-free survival compared to ipilimumab only in advanced melanoma patients. Anti-PD-1 therapy demonstrated nearly equal clinical efficacy in patients who had progressed after ipilimumab or were treatment-naïve. However, only limited evidence exists regarding the efficacy of ipilimumab alone or in combination with nivolumab after treatment failure to anti-PD-therapy. PATIENTS AND METHODS: A multicenter retrospective study in advanced melanoma patients who were treated with nivolumab (1 or 3 mg/kg) and ipilimumab (1 mg or 3 mg/kg) or ipilimumab (3 mg/kg) alone after treatment failure to anti-PD-1 therapy was performed. Patient, tumour, pre- and post-treatment characteristics were analysed. RESULTS: In total, 47 patients were treated with ipilimumab (ipi-group) and 37 patients with ipilimumab and nivolumab (combination-group) after treatment failure to anti-PD-1 therapy. Overall response rates for the ipi- and the combination-group were 16% and 21%, respectively. Disease control rate was 42% for the ipi-group and 33% for the combination-group. One-year overall survival rates for the ipi- and the combination-group were 54% and 55%, respectively. CONCLUSIONS: Ipilimumab should be considered as a viable treatment option for patients with failure to prior anti-PD-1 therapy, including those with progressive disease as best response to prior anti-PD-1. In contrast, the combination of ipilimumab and nivolumab appears significantly less effective in this setting compared to treatment-naïve patients.

14 Clinical Trial Nivolumab versus chemotherapy in patients with advanced melanoma who progressed after anti-CTLA-4 treatment (CheckMate 037): a randomised, controlled, open-label, phase 3 trial. 2015

Weber, Jeffrey S / D'Angelo, Sandra P / Minor, David / Hodi, F Stephen / Gutzmer, Ralf / Neyns, Bart / Hoeller, Christoph / Khushalani, Nikhil I / Miller, Wilson H / Lao, Christopher D / Linette, Gerald P / Thomas, Luc / Lorigan, Paul / Grossmann, Kenneth F / Hassel, Jessica C / Maio, Michele / Sznol, Mario / Ascierto, Paolo A / Mohr, Peter / Chmielowski, Bartosz / Bryce, Alan / Svane, Inge M / Grob, Jean-Jacques / Krackhardt, Angela M / Horak, Christine / Lambert, Alexandre / Yang, Arvin S / Larkin, James. ·Moffitt Cancer Center, Tampa, FL, USA. Electronic address: jeffrey.weber@moffitt.org. · Memorial Sloan-Kettering Cancer Center and Weill Cornell Medical College, New York, NY, USA. · California Pacific Center for Melanoma Research, San Francisco, CA, USA. · Dana-Farber Cancer Institute, Boston, MA, USA. · Medizinische Hochschule Hannover, Hannover, Germany. · Universitair Ziekenhuis Brussel, Brussels, Belgium. · Medical University of Vienna, Vienna, Austria. · Roswell Park Cancer Institute, Buffalo, NY, USA. · Segal Cancer Centre, Jewish General Hospital, McGill University, Montreal, QC, Canada. · University of Michigan, Ann Arbor, MI, USA. · Washington University, St Louis, MO, USA. · Centre Hospitalier Universitaire de Lyon, Lyon, France. · Christie Hospital, Manchester, UK. · Huntsman Cancer Institute, Salt Lake City, UT, USA. · German Cancer Research Centre University Hospital, Heidelberg, Germany. · Medical Oncology and Immunotherapy, University Hospital of Siena, Istituto Toscano Tumori, Siena, Italy. · Yale Cancer Center, New Haven, CT, USA. · Istituto Nazionale Tumori Fondazione G Pascale, Naples, Italy. · Elbe Kliniken Buxtehude, Buxtehude, Germany. · Department of Medicine, University of California, Los Angeles, CA, USA. · Department of Medicine, Mayo Clinic, Scottsdale, AZ, USA. · Department of Oncology, Herlev Hospital, Copenhagen, Denmark. · Aix-Marseille University, Hopital de la Timone, Marseille, France. · Technische Universität München School of Medicine, II Medical Department, Munich, Germany. · Bristol-Myers Squibb, Princeton, NJ, USA. · Bristol-Myers Squibb, Braine-I'Alleud, Belgium. · Royal Marsden Hospital, London, UK. ·Lancet Oncol · Pubmed #25795410.

ABSTRACT: BACKGROUND: Nivolumab, a fully human IgG4 PD-1 immune checkpoint inhibitor antibody, can result in durable responses in patients with melanoma who have progressed after ipilimumab and BRAF inhibitors. We assessed the efficacy and safety of nivolumab compared with investigator's choice of chemotherapy (ICC) as a second-line or later-line treatment in patients with advanced melanoma. METHODS: In this randomised, controlled, open-label, phase 3 trial, we recruited patients at 90 sites in 14 countries. Eligible patients were 18 years or older, had unresectable or metastatic melanoma, and progressed after ipilimumab, or ipilimumab and a BRAF inhibitor if they were BRAF(V 600) mutation-positive. Participating investigators randomly assigned (with an interactive voice response system) patients 2:1 to receive an intravenous infusion of nivolumab 3 mg/kg every 2 weeks or ICC (dacarbazine 1000 mg/m(2) every 3 weeks or paclitaxel 175 mg/m(2) combined with carboplatin area under the curve 6 every 3 weeks) until progression or unacceptable toxic effects. We stratified randomisation by BRAF mutation status, tumour expression of PD-L1, and previous best overall response to ipilimumab. We used permuted blocks (block size of six) within each stratum. Primary endpoints were the proportion of patients who had an objective response and overall survival. Treatment was given open-label, but those doing tumour assessments were masked to treatment assignment. We assessed objective responses per-protocol after 120 patients had been treated with nivolumab and had a minimum follow-up of 24 weeks, and safety in all patients who had had at least one dose of treatment. The trial is closed and this is the first interim analysis, reporting the objective response primary endpoint. This study is registered with ClinicalTrials.gov, number NCT01721746. FINDINGS: Between Dec 21, 2012, and Jan 10, 2014, we screened 631 patients, randomly allocating 272 patients to nivolumab and 133 to ICC. Confirmed objective responses were reported in 38 (31·7%, 95% CI 23·5-40·8) of the first 120 patients in the nivolumab group versus five (10·6%, 3·5-23·1) of 47 patients in the ICC group. Grade 3-4 adverse events related to nivolumab included increased lipase (three [1%] of 268 patients), increased alanine aminotransferase, anaemia, and fatigue (two [1%] each); for ICC, these included neutropenia (14 [14%] of 102), thrombocytopenia (six [6%]), and anaemia (five [5%]). We noted grade 3-4 drug-related serious adverse events in 12 (5%) nivolumab-treated patients and nine (9%) patients in the ICC group. No treatment-related deaths occurred. INTERPRETATION: Nivolumab led to a greater proportion of patients achieving an objective response and fewer toxic effects than with alternative available chemotherapy regimens for patients with advanced melanoma that has progressed after ipilimumab or ipilimumab and a BRAF inhibitor. Nivolumab represents a new treatment option with clinically meaningful durable objective responses in a population of high unmet need. FUNDING: Bristol-Myers Squibb.

15 Article Neoadjuvant BRAF-targeted therapy in regionally advanced and oligometastatic melanoma. 2020

Eroglu, Zeynep / Eatrides, Jennifer / Naqvi, Syeda Mahrukh Hussnain / Kim, Youngchul / Rich, Jeani / Babacan, Nalan Akgul / Brohl, Andrew S / Markowitz, Joseph / Sarnaik, Amod / Zager, Jonathan / Khushalani, Nikhil I / Sondak, Vernon K / Messina, Jane. ·Department of Cutaneous Oncology, Moffitt Cancer Center, Tampa, Florida. · Department of Biostatistics and Bioinformatics, Moffitt Cancer Center, Tampa, Florida. ·Pigment Cell Melanoma Res · Pubmed #31329344.

ABSTRACT: Current management of locoregional and oligometastatic melanoma is typically with surgery; however, some patients are unable to undergo resection due to location/size of their tumors and/or the anticipated morbidity of the surgery. While there are currently no established guidelines for neoadjuvant therapy in melanoma, neoadjuvant BRAF-targeted therapy may make resection more feasible. A retrospective analysis was conducted of 23 patients with BRAFV600-mutant, stage III/IV melanoma treated with BRAF-targeted therapy prior to surgery, with no adjuvant treatment. Surgical specimens, preoperative imaging, and clinical outcomes were evaluated. Results: Ten of 23 patients (44%) attained a pathologic complete response (pCR), with no correlation between RECIST response based on preoperative imaging and pathologic response. After a median of 43-month follow-up, only 1 patient (10%) with a pCR recurred, while 8 of 13 (62%) patients without a pCR recurred. Patients with a pCR had significantly improved relapse-free (RFS) and overall survival (OS) compared to patients with residual tumor. Neoadjuvant BRAF-targeted therapy is associated with a high pCR rate in patients with stage III-IV melanoma, which may correlate with improved RFS and OS.

16 Article Management of intussusception in patients with melanoma. 2019

Perez, Matthew C / Sun, James / Farley, Clara / Han, Dale / Sun, Alexander H / Narayan, Deepak / Lowe, Michael / Delman, Keith A / Messina, Jane L / Gonzalez, Ricardo J / Sondak, Vernon K / Khushalani, Nikhil I / Zager, Jonathan S. ·Department of Cutaneous Oncology, Moffitt Cancer Center, Tampa, Florida. · Division of Surgical Oncology, Emory University, Atlanta, Georgia. · Division of Surgical Oncology, Department of Surgery, Oregon Health and Science University, Portland, Oregon. · Department of Plastic and Reconstructive Surgery, Johns Hopkins University, Baltimore, Maryland. · Division of Plastic Surgery, Department of Surgery, Yale University, New Haven, Connecticut. ·J Surg Oncol · Pubmed #30734297.

ABSTRACT: BACKGROUND: Increased cross-sectional imaging for surveillance of metastatic melanoma has led to more diagnoses of asymptomatic intussusception. METHODS: We performed a multi-institutional retrospective review of patient records with a history of metastatic melanoma and a diagnosis of intussusception. Patients were divided into three groups: 1) asymptomatic patients without current evidence of melanoma (no evidence of disease [NED]); 2) asymptomatic intussusception and known active metastatic melanoma; 3) symptomatic intussusception and known active metastatic melanoma; the number of patients requiring surgery and intraoperative findings were recorded. RESULTS: We reviewed 73 patients diagnosed with intussusception from 2004 to 2017. Among asymptomatic patients with NED (n = 16), 14 spontaneously resolved and 2 underwent pre-emptive surgery without abnormal intraoperative findings. Of asymptomatic patients with active metastatic disease (n = 32), 25 were initially observed and 7 underwent pre-emptive surgery and 9 of the 25 initially observed patients required surgery for development of symptoms. In this group, all 16 patients undergoing surgery (50% of the group) had intraoperative findings of intussusception and/or metastatic intestinal melanoma.. All symptomatic patients with metastatic melanoma (n = 25) underwent surgery; all had intraoperative findings of intussusception and/or metastatic melanoma except 1 (Meckel's diverticulum). CONCLUSION: Asymptomatic patients with NED do not require surgery and intussusception will likely resolve spontaneously. Asymptomatic patients with known metastatic melanoma may be initially observed, but a low threshold for surgery should be maintained. Symptomatic patients with known metastases should undergo surgery.

17 Article Melanocortin 1 Receptor-Targeted α-Particle Therapy for Metastatic Uveal Melanoma. 2019

Tafreshi, Narges K / Tichacek, Christopher J / Pandya, Darpan N / Doligalski, Michael L / Budzevich, Mikalai M / Kil, HyunJoo / Bhatt, Nikunj B / Kock, Nancy D / Messina, Jane L / Ruiz, Epifanio E / Delva, Nella C / Weaver, Adam / Gibbons, William R / Boulware, David C / Khushalani, Nikhil I / El-Haddad, Ghassan / Triozzi, Pierre L / Moros, Eduardo G / McLaughlin, Mark L / Wadas, Thaddeus J / Morse, David L. ·Department of Cancer Physiology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida. · Department of Radiation Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida. · Department of Physics, University of South Florida, Tampa, Florida. · Department of Cancer Biology, Wake Forest University Health Sciences, Winston-Salem, North Carolina. · Small Animal Imaging Laboratory, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida. · Department of Pharmaceutical Sciences, Health Sciences Center, West Virginia University, and Modulation Therapeutics Inc., Morgantown, West Virginia. · Section on Comparative Medicine, Department of Pathology, Wake Forest University Health Sciences, Winston-Salem, North Carolina. · Departments of Anatomic Pathology and Cutaneous Pathology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida. · Department of Dermatology, University of South Florida, Tampa, Florida. · Department of Oncologic Sciences, University of South Florida, Tampa, Florida. · Division of Research Integrity and Compliance, University of South Florida, Tampa, Florida. · Biostatistics Core Facility, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida. · Department of Cutaneous Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida. · Departments of Diagnostic Imaging and Interventional Radiology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida; and. · Department of Hematology and Oncology, Wake Forest University Health Sciences, Winston-Salem, North Carolina. · Department of Cancer Physiology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida david.morse@moffitt.org. ·J Nucl Med · Pubmed #30733316.

ABSTRACT: New effective therapies are greatly needed for metastatic uveal melanoma, which has a very poor prognosis with a median survival of less than 1 y. The melanocortin 1 receptor (MC1R) is expressed in 94% of uveal melanoma metastases, and a MC1R-specific ligand (MC1RL) with high affinity and selectivity for MC1R was previously developed.

18 Article Melanoma central nervous system metastases: An update to approaches, challenges, and opportunities. 2019

Eroglu, Zeynep / Holmen, Sheri L / Chen, Qing / Khushalani, Nikhil I / Amaravadi, Ravi / Thomas, Reena / Ahmed, Kamran A / Tawbi, Hussein / Chandra, Sunandana / Markowitz, Joseph / Smalley, Inna / Liu, James K C / Chen, Yian Ann / Najjar, Yana G / Karreth, Florian A / Abate-Daga, Daniel / Glitza, Isabella C / Sosman, Jeffrey A / Sondak, Vernon K / Bosenberg, Marcus / Herlyn, Meenhard / Atkins, Michael B / Kluger, Harriet / Margolin, Kim / Forsyth, Peter A / Davies, Michael A / Smalley, Keiran S M. ·Moffitt Cancer Center, Tampa, Florida. · University of Utah Health Sciences Center, Salt Lake City, Utah. · The Wistar Institute, Philadelphia, Pennsylvania. · The University of Pennsylvania, Philadelphia, Pennsylvania. · Stanford University, Palo Alto, California. · MD Anderson Cancer Center, Houston, Texas. · Northwestern University, Chicago, Illinois. · University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania. · Yale University, New Haven, Connecticut. · Georgetown University Cancer Center, Washington, District of Columbia. · City of Hope, Duarte, California. ·Pigment Cell Melanoma Res · Pubmed #30712316.

ABSTRACT: In February 2018, the Melanoma Research Foundation and the Moffitt Cancer Center hosted the Second Summit on Melanoma Central Nervous System (CNS) Metastases in Tampa, Florida. In this white paper, we outline the current status of basic science, translational, and clinical research into melanoma brain metastasis development and therapeutic management. We further outline the important challenges that remain for the field and the critical barriers that need to be overcome for continued progress to be made in this clinically difficult area.

19 Article Interferon is associated with improved survival for node-positive cutaneous melanoma: a single-institution experience. 2018

Oliver, Daniel E / Sondak, Vernon K / Strom, Tobin / Zager, Jonathan S / Naghavi, Arash O / Sarnaik, Amod / Messina, Jane L / Caudell, Jimmy J / Trotti, Andy M / Torres-Roca, Javier F / Khushalani, Nikhil I / Harrison, Louis B. ·Department of Radiation Oncology, Moffitt Cancer Center, Tampa, FL 33612, USA. · Department of Oncologic Sciences, University of South Florida Morsani College of Medicine, Tampa, FL 33612, USA. · Department of Cutaneous Oncology, Moffitt Cancer Center, Tampa, FL 33612, USA. · Department of Radiation Oncology, University of Texas Southwestern, Dallas, TX 75390, USA. · Department of Anatomic Pathology, Moffitt Cancer Center, Tampa, FL 33612, USA. · Departments of Pathology & Cell Biology & Dermatology, University of South Florida Morsani College of Medicine, Tampa, FL 33612, USA. ·Melanoma Manag · Pubmed #30190928.

ABSTRACT: Aim: We assessed the role of adjuvant interferon on relapse-free survival (RFS), distant metastasis-free survival (DMFS) and overall survival (OS) in node-positive melanoma patients. Methods: We retrospectively reviewed 385 node-positive patients without distant metastatic disease treated from 1998 to 2015. The surgery was therapeutic lymph node dissection (LND, n = 86) or sentinel lymph node biopsy ± completion LND (n = 270). 128 patients (33.2%) received adjuvant interferon. Results: After a median follow-up of 70 months, interferon was associated with improved RFS (hazard ratio [HR]: 0.55; p < 0.001), DMFS (HR: 0.59; p < 0.001) and OS (HR: 0.61; p = 0.003), controlling for tumor and nodal stage, node size, sex, primary site, adjuvant therapy and extracapsular extension. In an exploratory age-matched comparison of patients treated with (n = 67) and without (n = 233) adjuvant immunotherapy, interferon still showed improved RFS, DMFS and OS. Conclusion: Adjuvant interferon appears to improve OS among node-positive melanoma patients in a modern experience, providing context for comparison in the adjuvant therapy landscape.

20 Article Combination of Ipilimumab and Adoptive Cell Therapy with Tumor-Infiltrating Lymphocytes for Patients with Metastatic Melanoma. 2018

Mullinax, John E / Hall, MacLean / Prabhakaran, Sangeetha / Weber, Jeffrey / Khushalani, Nikhil / Eroglu, Zeynep / Brohl, Andrew S / Markowitz, Joseph / Royster, Erica / Richards, Allison / Stark, Valerie / Zager, Jonathan S / Kelley, Linda / Cox, Cheryl / Sondak, Vernon K / Mulé, James J / Pilon-Thomas, Shari / Sarnaik, Amod A. ·Sarcoma Department, Moffitt Cancer Center, Tampa, FL, United States. · Immunology Department, Moffitt Cancer Center, Tampa, FL, United States. · Department of Surgery, University of New Mexico, Albuquerque, NM, United States. · NYU Langone Medical Center, New York, NY, United States. · Department of Cutaneous Oncology, Moffitt Cancer Center, Tampa, FL, United States. ·Front Oncol · Pubmed #29552542.

ABSTRACT: Purpose: Adoptive cell therapy (ACT) using tumor-infiltrating lymphocytes (TIL) for metastatic melanoma can be highly effective, but attrition due to progression before TIL administration (32% in prior institutional experience) remains a limitation. We hypothesized that combining ACT with cytotoxic T lymphocyte-associated antigen 4 blockade would decrease attrition and allow more patients to receive TIL. Experimental design: Thirteen patients with metastatic melanoma were enrolled. Patients received four doses of ipilimumab (3 mg/kg) beginning 2 weeks prior to tumor resection for TIL generation, then 1 week after resection, and 2 and 5 weeks after preconditioning chemotherapy and TIL infusion followed by interleukin-2. The primary endpoint was safety and feasibility. Secondary endpoints included of clinical response at 12 weeks and at 1 year after TIL transfer, progression free survival (PFS), and overall survival (OS). Results: All patients received at least two doses of ipilimumab, and 12 of the 13 (92%) received TIL. A median of 6.5 × 10 Conclusion: Ipilimumab plus ACT for metastatic melanoma is feasible, well tolerated, and associated with a low rate of attrition due to progression during cell expansion. This combination approach serves as a model for future efforts to improve the efficacy of ACT.

21 Article Higher than reported adolescent and young adult clinical trial enrollment during the "Golden Age" of melanoma clinical trials. 2018

Sreeraman Kumar, Radhika / Thapa, Ram / Kim, Youngchul / Khushalani, Nikhil I / Sondak, Vernon K / Reed, Damon R. ·Department of Radiation Oncology, Moffitt Cancer Center, Tampa, Florida, 33612. · Department of Biostatistics and Bioinformatics, Moffitt Cancer Center, Tampa, Florida, 33612. · Department of Cutaneous Oncology, Moffitt Cancer Center, Tampa, Florida, 33612. · Adolescent and Young Adult Program, Moffitt Cancer Center, Tampa, Florida, 33612. · Sarcoma Department, Moffitt Cancer Center, Tampa, Florida, 33612. · Chemical Biology and Molecular Medicine Program, Moffitt Cancer Center, Tampa, Florida, 33612. ·Cancer Med · Pubmed #29478277.

ABSTRACT: Clinical trial enrollments in adolescents and young adults (AYA) with cancer have historically been lower than those in pediatric and older adult populations. We sought to examine therapeutic trial enrollment rates at our cancer center. We performed a retrospective evaluation of AYA patients treated before and after the first checkpoint inhibitor trial opened at our cancer center in 2007. We examined gender, stage at presentation and insurance status in terms of trial enrollment. We compared the trial participation rate of AYA patients with that of older adults. In this adult facility, 12.7% (1,831) of total patients were between age 15 and 39. Overall therapeutic clinical trial rate was 17.6% which increased to 19.8% since 2007. Both nodal disease or metastatic disease at presentation was associated with increasing odds of trial enrollment (OR = 5.36 and P < 0.001 for nodal disease and OR = 7.96 and P < 0.001 for metastatic disease). There was a nonstatistically significant trend toward improved 3-year overall survival in the AYA patients with advanced presentation that enrolled on clinical trials compared with those not enrolled on trials since 2007. AYA clinical trial enrollment at a comprehensive care center melanoma program was higher than reported in the literature overall for AYA patients. This 1,831 patient cohort may provide a foundation for more detailed investigation toward quantifying the effects of clinical trial enrollment in terms of age-specific benefits and toxicities for AYA patients with malignancies that have their peak incidence in older adults.

22 Article Duration of Anti-Programmed Death-1 Therapy in Advanced Melanoma: How Much of a Good Thing Is Enough? 2018

Khushalani, Nikhil I. ·Nikhil I. Khushalani, H. Lee Moffitt Cancer Center, Tampa, FL. ·J Clin Oncol · Pubmed #29389234.

ABSTRACT: The Oncology Grand Rounds series is designed to place original reports published in the Journal into clinical context. A case presentation is followed by a description of diagnostic and management challenges, a review of the relevant literature, and a summary of the authors' suggested management approaches. The goal of this series is to help readers better understand how to apply the results of key studies, including those published in Journal of Clinical Oncology, to patients seen in their own clinical practice. A 53-year-old healthy man presented with recurrent in-transit melanoma of the right lower extremity. Eight years prior he had undergone wide local excision and sentinel lymph node biopsy for invasive melanoma of the anteromedial aspect of the distal right thigh. Pathology revealed an ulcerated melanoma, Breslow depth 3.5 mm, and with one involved micrometastatic inguinal lymph node. Staging studies did not demonstrate distant metastases. Superficial inguinal node dissection was performed and did not identify any additional metastatic nodes of 14 retrieved for a final pathologic staging of T3bN1aM0 (stage IIIB) cutaneous melanoma. He received 12 months of adjuvant high-dose interferon alfa-2b. Two years later, he developed a 1.2-cm subcutaneous focus of in-transit recurrence approximately 4 cm proximal to the original melanoma site in the right thigh, which was treated with surgical resection followed by adjuvant radiotherapy. Over the next 4 years, he underwent six additional surgeries for isolated in-transit recurrences affecting the same limb. He was referred for therapeutic options at the time of his latest in-transit recurrence. Examination revealed three palpable subcutaneous nodules in the right thigh in the setting of lymphedema. A core biopsy confirmed recurrent melanoma (Fig 1). Whole-body fluorodeoxyglucose positron emission tomography imaging revealed at least 17 hypermetabolic cutaneous and subcutaneous nodules in the right thigh, four fluorodeoxyglucose-avid nodules below the right knee, but no distant metastases (Fig 2A). Brain magnetic resonance imaging was normal. His serum chemistry profile, including lactate dehydrogenase, was normal. Molecular analysis demonstrated presence of BRAF V600E mutation in the tumor. After multidisciplinary evaluation, an isolated limb infusion procedure of the right lower extremity was not believed to be feasible, secondary to the proximal extent of the recurrence. Therapy was initiated with pembrolizumab at 2 mg/kg intravenously every 3 weeks.

23 Article Adjuvant and Neoadjuvant Therapy in High-Risk Stage III Cutaneous Melanoma. 2017

Sondak, Vernon K / Khushalani, Nikhil I. ·Department of Cutaneous Oncology, Moffitt Cancer Center, and Department of Oncologic Sciences, USF Morsani College of Medicine, Tampa, Florida. ·Int J Radiat Oncol Biol Phys · Pubmed #28586957.

ABSTRACT: -- No abstract --

24 Article Regional Radiation Therapy Impacts Outcome for Node-Positive Cutaneous Melanoma. 2017

Strom, Tobin / Torres-Roca, Javier F / Parekh, Akash / Naghavi, Arash O / Caudell, Jimmy J / Oliver, Daniel E / Messina, Jane L / Khushalani, Nikhil I / Zager, Jonathan S / Sarnaik, Amod / Mulé, James J / Trotti, Andy M / Eschrich, Steven A / Sondak, Vernon K / Harrison, Louis B. ·Department of Radiation Oncology, Moffitt Cancer Center and Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, Texas · Department of Oncologic Sciences, University of South Florida Morsani College of Medicine · Department of Cutaneous Oncology, Moffitt Cancer Center · Department of Pathology & Cell Biology and Dermatology, University of South Florida Morsani College of Medicine · Center for Translational Research, Moffitt Cancer Center · Department of Biomedical Informatics, Moffitt Cancer Center, Tampa, Florida ·J Natl Compr Canc Netw · Pubmed #28404758.

ABSTRACT:

25 Article A phase IB study of ipilimumab with peginterferon alfa-2b in patients with unresectable melanoma. 2016

Brohl, Andrew S / Khushalani, Nikhil I / Eroglu, Zeynep / Markowitz, Joseph / Thapa, Ram / Chen, Y Ann / Kudchadkar, Ragini / Weber, Jeffrey S. ·Department of Cutaneous Oncology, H. Lee Moffitt Cancer Center and Research Institute, 12902 Magnolia Drive, Tampa, FL 33612-9416 USA. · Department of Biostatistics and Bioinformatics, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL USA. · Winship Cancer Institute of Emory University, Atlanta, GA USA. · Department of Cutaneous Oncology, H. Lee Moffitt Cancer Center and Research Institute, 12902 Magnolia Drive, Tampa, FL 33612-9416 USA ; New York University Langone Medical Center, New York, NY USA. ·J Immunother Cancer · Pubmed #28031816.

ABSTRACT: BACKGROUND: Ipilimumab and peginterferon alfa-2b are established systemic treatment options for melanoma that have distinct mechanisms of action. Given the need for improved therapies for advanced melanoma, we conducted an open-label, single institution, phase Ib study to assess the safety and tolerability of using these two agents in combination. METHODS: Study treatment consisted of ipilimumab given every 3 weeks, for a total of four infusions, concurrent with peginterferon alfa-2b administered subcutaneous weekly for a total of 12 weeks. This was followed by maintenance therapy with peginterferon alfa-2b administered subcutaneously weekly for up to 144 additional weeks. The study was designed as a two-stage dose escalation scheme with continuous dose-limiting toxicity monitoring during the induction phase. RESULTS: Thirty one patients received at least 1 dose of study treatment and 30 were assessable for efficacy endpoints. We found that ipilimumab at 3 mg/kg dosing with peginterfeon alfa-2b at 2 μg/kg/week was the maximum tolerated dose of this combination. The incidence of grade 3 drug-related adverse events (AEs) was 45.2%. There were no grade 4/5 AEs. The overall response rate was 40% by immune-related response criteria. Median progression-free survival was 5.9 months. The median overall survival was not reached with at a median follow-up of 35.8 months. CONCLUSIONS: We report that the combination of ipilimumab at 3 mg/kg dosing combined with peginterfeon alfa-2b at 2 μg/kg/week demonstrated an acceptable toxicity profile and a promising efficacy signal. Further study of this combination is warranted. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01496807, Registered December 19th, 2011.

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