Angeles Clinic and Research Institute

Los Angeles, CA, United States

Angeles Clinic and Research Institute

Los Angeles, CA, United States
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News Article | February 15, 2017

Physicians’ Education Resource® (PER®), will host the 13th Annual International Symposium on Melanoma and Other Cutaneous Malignancies® on Feb. 11 at Trump International Miami. The program will be led by Co-Chairs Dr. Jeffrey S. Weber, deputy director of the Laura and Issac Perlmutter Cancer Center and professor of medicine at NYU’s Langone Medical Center, and Dr. Omid Hamid, chief of translational and immuno-oncology and director of cutaneous malignancies at the Angeles Clinic and Research Institute and Director of Experimental Therapeutics at Cedars Sinai Medical Care Foundation in Los Angeles. In making the announcement, Dr. Jeffery S. Weber said: “We have just begun to scratch the surface in the process of developing the innovative techniques and therapies that we can use to fight cutaneous malignancies. Interactive forums like the current one allow those on the front lines to collaborate in order to propel the right initiatives forward to improve patient care.” The one-day educational meeting’s focal point will be on contemporary approaches and the future of direction of therapy in the management of melanoma and other cutaneous malignancies, and contains a fast-paced forum on key core areas of personalizing care for melanoma tumors including immunotherapies, targeted therapies, regional therapy, predictive/prognostic modeling, and integrated medicine/patient care. The symposium will be held at the Trump International Miami on Feb. 11 in Sunny Isles Beach, Florida, located 3.5 miles from the Miami International Airport and 13 miles from the Fort Lauderdale International Airport. For more information and to register please visit: About PER® Since 1995, PER has been the educational resource of choice for live and online activities focusing on oncology and hematology. PER provides high-quality, evidence-based activities featuring leading national and international faculty with a focus on practice-changing advances and standards of care in treatment and disease management. Activities also include topics on emerging strategies currently under investigation, supportive care, diagnosis and staging, prevention, screening and early detection, and practice management. With the rapid advances occurring in the field of oncology, understanding how to use molecular data to diagnose and stage patients, selecting the most appropriate candidates for novel therapeutic agents, individualizing treatment based on tumor type, and referring patients to clinical trials will continue to ensure the highest level of patient care is provided. PER serves the oncology healthcare community, including physicians, fellows, advanced practice nurses, nurses, physician assistants, pharmacists, and researchers. PER is part of the Cranbury, N.J.-based Michael J. Hennessy Associates, Inc. family of businesses. Learn more at and

Hamid O.,Angeles Clinic and Research Institute | Robert C.,Institute Gustave Roussy | Daud A.,University of California at San Francisco | Hodi F.S.,Dana-Farber Cancer Institute | And 22 more authors.
New England Journal of Medicine | Year: 2013

BACKGROUND: The programmed death 1 (PD-1) receptor is a negative regulator of T-cell effector mechanisms that limits immune responses against cancer. We tested the anti-PD-1 antibody lambrolizumab (previously known as MK-3475) in patients with advanced melanoma. METHODS: We administered lambrolizumab intravenously at a dose of 10 mg per kilogram of body weight every 2 or 3 weeks or 2 mg per kilogram every 3 weeks in patients with advanced melanoma, both those who had received prior treatment with the immune checkpoint inhibitor ipilimumab and those who had not. Tumor responses were assessed every 12 weeks. RESULTS: A total of 135 patients with advanced melanoma were treated. Common adverse events attributed to treatment were fatigue, rash, pruritus, and diarrhea; most of the adverse events were low grade. The confirmed response rate across all dose cohorts, evaluated by central radiologic review according to the Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1, was 38% (95% confidence interval [CI], 25 to 44), with the highest confirmed response rate observed in the cohort that received 10 mg per kilogram every 2 weeks (52%; 95% CI, 38 to 66). The response rate did not differ significantly between patients who had received prior ipilimumab treatment and those who had not (confirmed response rate, 38% [95% CI, 23 to 55] and 37% [95% CI, 26 to 49], respectively). Responses were durable in the majority of patients (median follow-up, 11 months among patients who had a response); 81% of the patients who had a response (42 of 52) were still receiving treatment at the time of analysis in March 2013. The overall median progression-free survival among the 135 patients was longer than 7 months. CONCLUSIONS: In patients with advanced melanoma, including those who had had disease progression while they had been receiving ipilimumab, treatment with lambrolizumab resulted in a high rate of sustained tumor regression, with mainly grade 1 or 2 toxic effects. Copyright © 2013 Massachusetts Medical Society.

Minor D.R.,University of California at San Francisco | Kashani-Sabet M.,University of California at San Francisco | Garrido M.,University of California at San Francisco | O'Day S.J.,Angeles Clinic and Research Institute | And 2 more authors.
Clinical Cancer Research | Year: 2012

Purpose: Recent studies have shown activating KIT mutations in melanoma originating from mucosa, acral, or cumulative sun-damaged skin sites. We aimed to assess the predictive role of KIT mutation, amplification, or overexpression for response to treatment with the kinase inhibitor sunitinib. Experimental Design: Tumor tissues from 90 patients with stage III or IV acral, mucosal, or cumulative sun-damaged skin melanoma underwent sequencing of KIT, BRAF, NRAS, and GNAQ genes, FISH analysis for KIT amplification, and immunohistochemistry of KIT protein (CD117). Patients with mutations, amplifications, or overexpression of KIT were treated with sunitinib and responses measured by Response Evaluation Criteria in Solid Tumors (RECIST). Results: Eleven percent of the melanomas tested had mutations in KIT, 23% in BRAF, 14% in NRAS, and none in GNAQ. Of 12 patients treated with sunitinib, 10 were evaluable. Of the 4 evaluable patients with KIT mutations, 1 had a complete remission for 15 months and 2 had partial responses (1- and 7-month duration). In contrast, only 1 of the 6 patients with only KIT amplification or overexpression alone had a partial response. In 1 responder with rectal melanoma who later progressed, the recurring tumor had a previously undetected mutation in NRAS, which was found in addition to the persisting mutation in KIT. Interestingly, among patients with manifest stage IV disease, KIT mutations were associated with a significantly shortened survival time (P < 0.0001). Conclusions: Sunitinib may have activity in patients with melanoma and KIT mutations; more study is needed. KIT mutations may represent an adverse prognostic factor in metastatic melanoma. ©2012 AACR.

Herbst R.S.,Yale University | Soria J.-C.,Gustave Roussy South Paris University | Kowanetz M.,Genentech | Fine G.D.,Genentech | And 18 more authors.
Nature | Year: 2014

The development of human cancer is a multistep process characterized by the accumulation of genetic and epigenetic alterations that drive or reflect tumour progression. These changes distinguish cancer cells from their normal counterparts, allowing tumours to be recognized as foreign by the immune system1-4. However, tumours are rarely rejected spontaneously, reflecting their ability to maintain an immunosuppressive microenvironment5. Programmed death-ligand 1 (PD-L1; also called B7-H1 or CD274), which is expressed on many cancer and immune cells, plays an important part in blocking the 'cancer immunity cycle' by binding programmed death-1 (PD-1) and B7.1 (CD80), both of which are negative regulators of T-lymphocyte activation. Binding of PD-L1 to its receptors suppresses T-cell migration, proliferation and secretion of cytotoxic mediators, and restricts tumour cell killing6-10. The PD-L1-PD-1 axis protects the host from overactive T-effector cells not only in cancer but also during microbial infections11. Blocking PD-L1 should therefore enhance anticancer immunity, but little is known about predictive factors of efficacy. This study was designed to evaluate the safety, activity and biomarkers of PD-L1 inhibition using the engineered humanized antibody MPDL3280A. Here we show that across multiple cancer types, responses (as evaluated by Response Evaluation Criteria in Solid Tumours, version 1.1) were observed in patients with tumours expressing high levels of PD-L1, especially when PD-L1 was expressed by tumour-infiltrating immune cells. Furthermore, responses were associated with T-helper type 1 (TH 1) gene expression, CTLA4 expression and the absence of fractalkine (CX3CL1) in baseline tumour specimens. Together, these data suggest that MPDL3280A is most effective in patients in which pre-existing immunity is suppressed by PD-L1, and is re-invigorated on antibody treatment. © 2014 Macmillan Publishers Limited. All rights reserved.

Garon E.B.,University of California at Los Angeles | Rizvi N.A.,Columbia University | Hui R.,University of Sydney | Leighl N.,Princess Margaret Cancer Center | And 23 more authors.
New England Journal of Medicine | Year: 2015

BACKGROUND: We assessed the efficacy and safety of programmed cell death 1 (PD-1) inhibition with pembrolizumab in patients with advanced non-small-cell lung cancer enrolled in a phase 1 study. We also sought to define and validate an expression level of the PD-1 ligand 1 (PD-L1) that is associated with the likelihood of clinical benefit. METHODS: We assigned 495 patients receiving pembrolizumab (at a dose of either 2 mg or 10 mg per kilogram of body weight every 3 weeks or 10 mg per kilogram every 2 weeks) to either a training group (182 patients) or a validation group (313 patients). We assessed PD-L1 expression in tumor samples using immunohistochemical analysis, with results reported as the percentage of neoplastic cells with staining for membranous PD-L1 (proportion score). Response was assessed every 9 weeks by central review. RESULTS: Common side effects that were attributed to pembrolizumab were fatigue, pruritus, and decreased appetite, with no clear difference according to dose or schedule. Among all the patients, the objective response rate was 19.4%, and the median duration of response was 12.5 months. The median duration of progression-free survival was 3.7 months, and the median duration of overall survival was 12.0 months. PD-L1 expression in at least 50% of tumor cells was selected as the cutoff from the training group. Among patients with a proportion score of at least 50% in the validation group, the response rate was 45.2%. Among all the patients with a proportion score of at least 50%, median progression-free survival was 6.3 months; median overall survival was not reached. CONCLUSIONS: Pembrolizumab had an acceptable side-effect profile and showed antitumor activity in patients with advanced non-small-cell lung cancer. PD-L1 expression in at least 50% of tumor cells correlated with improved efficacy of pembrolizumab. Copyright © 2015 Massachusetts Medical Society.

Ledezma B.,University of California at Los Angeles | Heng A.,Angeles Clinic and Research Institute
Cancer Management and Research | Year: 2014

After decades without promising new treatments for advanced and metastatic melanoma, ipilimumab was the first systemic therapy approved for use in this patient population. A fully human monoclonal antibody that blocks cytotoxic T-lymphocyte antigen 4 (CTLA-4) to augment antitumor T-cell responses, ipilimumab significantly extended overall survival in clinical trials. Because ipilimumab is associated with a set of immune-related adverse events that likely reflect the agent's mechanism of action, a management guide has been established. Nurses play a significant role in initially identifying these adverse reactions and assisting in patient education, treatment, and follow-up. Herein, we discuss commonly asked questions related to ipilimumab therapy and treatment of adverse events, and how nurses can be prepared to answer these questions as they arise from patients and caregivers. © 2014 Ledezma and Heng, This work is published by Dove Medical Press Limited.

Goldenberg G.,Mount Sinai School of Medicine | Hamid O.,Angeles Clinic and Research Institute
Journal of Drugs in Dermatology | Year: 2013

Basal cell carcinoma (BCC) is the most common cancer in the world. It is typically slow growing and usually effectively managed with surgery. However, BCCs in some patients are unsuitable for surgery or the patient may prefer a nonsurgical treatment. Radiotherapy is a nonsurgical option for the primary treatment of either low- or high-risk BCCs. It is associated with high cure rates, albeit somewhat lower than those observed with Mohs micrographic surgery for high-risk BCCs. Not all patients with BCCs are suitable for radiotherapy. Superficial therapies for BCC include topical imiquimod or 5- fluorouracil and photodynamic therapy (PDT). These therapies are generally associated with somewhat lower clearance rates and/or higher recurrence rates than surgery or radiotherapy, although they may be suitable in patients with low-risk BCCs when surgery or radiotherapy are impractical or less appropriate. An appealing feature of PDT is excellent cosmesis, but PDT is not currently approved by the Food and Drug Administration (FDA), and regimens are not well standardized. Vismodegib is a first-in-class hedgehog pathway inhibitor and recent addition to the armamentarium for the treatment of advanced BCC. Copyright © 2013 Journal of Drugs in Dermatology.

Hamid O.,Angeles Clinic and Research Institute | Goldenberg G.,Mount Sinai School of Medicine
Journal of Drugs in Dermatology | Year: 2013

Basal cell carcinoma (BCC) is a common skin cancer and its incidence is on the rise worldwide. Clinical presentation and histologic examination are used for diagnosis and to stratify BCCs as either low- or high-risk for recurrence or development of advanced disease. A number of surgical and nonsurgical options are available for BCC. BCC is most often managed with a surgical approach, but not all tumors and patients are suitable for surgery. Vismodegib is a recently approved first-in-class hedgehog pathway inhibitor that has expanded options for patients who have locally advanced or metastatic BCC. Copyright © 2013.

Boasberg P.,Angeles Clinic and Research Institute | Hamid O.,Angeles Clinic and Research Institute | O'Day S.,Angeles Clinic and Research Institute
Seminars in Oncology | Year: 2010

Malignant melanoma is rising faster in incidence than any other malignancy. Long-term remission or "cure" is rare and is almost exclusively limited to therapies that stimulate an immune antitumor response. Ipilimumab is a novel targeted human immunostimulatory monoclonal antibody that blocks cytotoxic T-lymphocyte antigen4 (CTLA-4), an immune-inhibitory site expressed on activated T cells. Ipilimumab is well tolerated as an outpatient infusion therapy. Multiple studies have confirmed significant antimelanoma activity. A randomized trial has documented a survival benefit when ipilimumab was compared to a gp-100 vaccine only arm. The unique mechanism of action of ipilimumab makes assessment of response by conventional criteria difficult. Benefit from ipilimumab can occur after what would be considered progression with World Health Oganization (WHO) or Response Evaluation Criteria in Solid Tumors (RECIST) criteria. New immune response criteria have been proposed. Therapeutic responses peak between 12 and 24 weeks, with slow responses continuing up to and beyond 12 months. The major drug- related adverse side effects (10%15% grade 3 or above) are immune-related and consist most commonly of rash, colitis, hypophysitis, thyroiditis, and hepatitis. Colonic perforation can occur and patients with diarrhea have to be monitored carefully with strict adherence to treatment algorithms. Algorithms for the treatment of other adverse side effects have been developed. The treatment of immune-related side effects with immunosuppressive agents, such as corticosteroids, does not appear to impair antitumor response. With proper monitoring and management of side effects, ipilimumab is an extremely safe drug to administer. The benefits of ipilimumab will most certainly extend to other malignancies in the near future. © 2010 Published by Elsevier Inc.

Hamid O.,Angeles Clinic and Research Institute | Carvajal R.D.,Sloan Kettering Cancer Center
Expert Opinion on Biological Therapy | Year: 2013

Introduction: Multiple agents targeting the immune "checkpoint" programmed death-1 (PD-1) pathway have demonstrated early evidence of durable clinical activity and an encouraging safety profile in patients with various tumor types, including some cancers, such as non-small-cell lung cancer, historically perceived as non-immunogenic and thus nonresponsive to immunotherapy. Areas covered: Functions of the PD-1 pathway in normal immune responses are reviewed, along with the significance of expression of PD-1 and its ligands in malignant settings. Rationale for the development of PD-1 pathway-targeted therapies and associated clinical data are presented. Finally, efforts to date to identify and develop partner predictive or prognostic biomarkers for these new PD-1 pathway-targeted immunotherapies are discussed. Expert opinion: Rather than targeting the tumor directly, immunotherapies inhibiting PD-1 pathway signaling modulate the antitumor immune response. Indeed, these agents have already demonstrated promising antitumor activity and manageable toxicity in various cancers. If future data continue to support encouraging clinical profiles of anti-PD-1 and anti-programmed death-ligand 1 antibodies, the current paradigm of cancer therapy may shift. In select patient populations (ideally identified by a predictive biomarker), PD-1 pathway-targeted immunotherapy has the potential to serve as the backbone of cancer treatment, and trials evaluating combinations with chemotherapy and/or molecularly targeted therapies will determine whether additive or even synergistic responses can be achieved. © 2013 Informa UK, Ltd.

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