The second seminar of our eight-part online, integrated educational course on issues relevant to the current and future treatment of several different solid tumors and hematologic cancers features Drs Keith T Flaherty, Adriano Piris and Jeffrey Weber. Part II (originally held June 21, 2011) features discussion of the latest clinical research data sets in melanoma. (Webinar)
CE Disclosures and Faculty Information
TARGET AUDIENCE
This activity is intended for medical oncologists, hematology-oncology fellows and other healthcare providers involved in the treatment of melanoma.
OVERVIEW OF ACTIVITY
Between the 1960s and the 1990s, the incidence of melanoma and the mortality rates associated with this disease rose precipitously in most developed and industrialized nations around the world. Despite increased awareness of this phenomenon and extensive attempts to publicize risk factors and screening, current estimates suggest that 68,130 men and women were diagnosed with melanoma and 8,700 individuals died from the disease in 2010 within the United States alone.
Although most patients with in situ or early-stage melanoma may be cured by primary excision in the absence of systemic therapy, the prognosis of patients with metastatic melanoma remains poor. The disappointing impact of existing interventions on clinical outcomes in Stage IV disease has resulted in a need to continue to investigate novel treatment options for patients. Novel treatments exploiting the biologic and genomic characteristics of melanomatous tumors have made this disease a fertile ground for application of emerging systemic therapeutics.
This program uses a review of recent ASCO papers and other relevant publications, faculty case presentations, Q&A, discussion of community practice patterns and a melanoma pathology tutorial to assist practicing clinicians with the incorporation of investigational findings from the multitude of diverse ongoing trials into routine clinical care.
LEARNING OBJECTIVES- Use case-based learning to individualize the care of patients with metastatic melanoma.
- Communicate the benefits and risks of ipilimumab-based therapy to appropriately selected patients with advanced-stage melanoma.
- Recall emerging data with BRAF inhibitors in the targeted treatment of melanoma, and identify how these agents may affect diagnosis and management of the disease.
ACCREDITATION STATEMENT
Research To Practice is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.
CME credit is no longer available for this issue
CREDIT DESIGNATION STATEMENT
CME credit is no longer available for this issue
HOW TO USE THIS CME ACTIVITY
CME credit is no longer available for this issue
This CME activity consists of two video components. The participant should watch the videos.
CONTENT VALIDATION AND DISCLOSURES
Research To Practice (RTP) is committed to providing its participants with high-quality, unbiased and state-of-the-art education. We assess potential conflicts of interest with faculty, planners and managers of CME activities. Real or apparent conflicts of interest are identified and resolved through a conflict of interest resolution process. In addition, all activity content is reviewed by both a member of the RTP scientific staff and an external, independent physician reviewer for fair balance, scientific objectivity of studies referenced and patient care recommendations.
FACULTY — The following faculty (and their spouses/partners) reported real or apparent conflicts of interest, which have been resolved through a conflict of interest resolution process:
Keith T Flaherty, MD
Associate Professor, Harvard Medical School
Director of Developmental Therapeutics
Massachusetts General Hospital Cancer Center
Boston, Massachusetts
Advisory Committee: Bristol-Myers Squibb Company, Eisai Inc, Genentech BioOncology; Consulting Agreements: Cephalon Inc, GlaxoSmithKline.
Adriano Piris, MD
Dermatopathologist, Massachusetts General Hospital
Director, Quality and Safety Division, MGH Dermatopathology
Instructor of Pathology, Harvard Medical School
Boston, Massachusetts
No real or apparent conflicts of interest to disclose.
Jeffrey Weber, MD, PhD
Senior Member, H Lee Moffitt Cancer Center
Director, Donald A Adam Comprehensive Melanoma Research Center
Tampa, Florida
Advisory Committee: Bristol-Myers Squibb Company, Celldex Inc, Genentech BioOncology, Novartis Pharmaceuticals Corporation; Consulting Agreement: Bristol-Myers Squibb Company; Stock Ownership: Celldex Inc.
MODERATOR — Dr Love is president and CEO of Research To Practice, which receives funds in the form of educational grants to develop CME activities from the following commercial interests: Allos Therapeutics, Amgen Inc, AstraZeneca Pharmaceuticals LP, Aureon Laboratories Inc, Bayer HealthCare Pharmaceuticals/Onyx Pharmaceuticals Inc, Biogen Idec, Boehringer Ingelheim Pharmaceuticals Inc, Bristol-Myers Squibb Company, Celgene Corporation, Cephalon Inc, Daiichi Sankyo Inc, Dendreon Corporation, Eisai Inc, EMD Serono Inc, Genentech BioOncology, Genomic Health Inc, ImClone Systems, a wholly owned subsidiary of Eli Lilly and Company, Lilly USA LLC, Millennium: The Takeda Oncology Company, Mundipharma International Limited, Myriad Genetics Inc, Novartis Pharmaceuticals Corporation, OSI Oncology, Sanofi and Seattle Genetics.
RESEARCH TO PRACTICE STAFF AND EXTERNAL REVIEWERS — The scientific staff and reviewers for Research To Practice have no real or apparent conflicts of interest to disclose.
This educational activity contains discussion of published and/or investigational uses of agents that are not indicated by the Food and Drug Administration. Research To Practice does not recommend the use of any agent outside of the labeled indications. Please refer to the official prescribing information for each product for discussion of approved indications, contraindications and warnings. The opinions expressed are those of the presenters and are not to be construed as those of the publisher or grantors.
This program is supported by educational grants from Bristol-Myers Squibb Company and Genentech BioOncology.
Hardware/Software Requirements:
An Internet connection that is at least 28.8 Kbps
A monitor set to 1280 x 1024 pixels or more
Internet Explorer 6.x or newer, Firefox 2.x or newer, or Safari 2.x or newer
Macromedia Flash plug-in 6.0 or greater
Adobe Acrobat Reader
(Optional) Sound card and speakers for audio
Last review date: June 2011
Expiration date: June 2012
Acknowledge and close
(WiFi is recommended for best performance):
During last week’s RTP TV episode featuring melanoma mavens Jeff Weber and the aforementioned Keith Flaherty, we spent most of our time reviewing two more stunning plenary data sets just presented in Chicago and simultaneously published in the New England Journal that bring to a crescendo these landmark strategies and offer real hope in a disease that often affects people in the prime of their lives. Here are a few notes from one of the quickest hours in CME history:
1. Ipilimumab
The Phase III study presented during the plenary session by Jedd Wolchok evaluated DTIC alone or in combination with — as Keith calls it — “Ipi,” and although the impact on short-term variables like response rate and PFS were modest, as seen in prior studies, 20 to 30 percent of patients experienced prolonged survival. Related to this phenomenon, on our webcast Dr Weber presented a 32-year-old patient receiving Ipi on trial who experienced a complete response and is alive and well eight years later. Currently there are no specific clinical or tissue predictors of benefit with this interesting antibody that “blocks the brakes” on T-cell activation, but of particular note is a diverse array of potential immune-related treatment complications. These include a bothersome colitis that both investigators emphasized must be treated promptly with corticosteroids rather than medications like Imodium, pruritus, which can usually be managed with topical corticosteroids, and more uncommonly hypophysitis that may present clinically as fatigue and/or more specific endocrine manifestations. Interestingly, during an unrelated audio interview I conducted with Dr Wolchok on the same day as the webcast he discussed a patient responding to Ipi who was experiencing decreased libido. Sure enough, the patient had pituitary enlargement on MRI and a hypopit endocrine profile.
2. Vemurafenib
One of the exciting new “ibs” discussed in Dr Sledge’s presidential address, vemurafenib is restricted to the 40 to 60 percent of patients with melanoma harboring a BRAF V600E mutation. As was seen in the plenary data set comparing it to DTIC, many of the treated patients experienced objective tumor shrinkage, although this may be short-lived due to a multitude of other mutations that allow the tumor rather than the patient to survive. During the broadcast, both faculty members showed scans from individuals who clearly benefited from this agent, and one strategy being discussed for future trials for patients with BRAF mutation-positive tumors is the combination of Ipi and V-mib. To continue the story of melanoma agents with unusual toxicities, vemurafenib and other V600E BRAF inhibitors not infrequently cause the relatively rapid development of skin keratoacanthomas and actual squamous cell carcinomas. Keith noted that there is a logical biologic explanation for this observation in terms of upregulation of a complementary tumor-activating pathway, and at ASCO the “king of dermato-oncology,”
Although vemurafenib is currently not approved, the faculty speculated on how they might go about sequencing it with Ipi for patients with BRAF mutation-positive tumors if and when the drug becomes available. Jeff felt that the impressive waterfall plots may motivate practitioners to turn to the “ib” first, but for patients who are clinically stable and not in need of immediate tumor response both faculty members believe that Ipi is an equally logical up-front choice. Other strategies that may soon follow include trials of these interesting molecules in the adjuvant setting, and in that regard, please click here for a pathology video tutorial with Dr Adriano Piris on primary melanoma and prognosis.
Next up on our webcast summary series, we review ASCO data sets and faculty cases related to Dr Sledge’s prototypical “smart cancer,” non-small cell lung carcinoma, which was discussed during our most recent RTP TV broadcast this past Tuesday night.
Neil Love, MD
Research To Practice
Miami, Florida