Choosing a melanoma therapy with Dr. Justine Cohen

Thursday, October 17, 2019

Justine V. Cohen, DO, of the University of Pennsylvania, Philadelphia, joins Blood & Cancer host David H. Henry, MD, also of the University of Pennsylvania, to discuss a recent melanoma case in the adjuvant setting and when to consider targeted therapies or immune checkpoint inhibitors for these patients.

Plus, in Clinical Correlation, Ilana Yurkiewicz, MD, of Stanford (Calif.) University, talks about what happens when a patient’s anxiety threatens to get in the way of the clinician’s decision making.

Time stamps:

  • Meet the guest (00:51)
  • This Week in Oncology (03:02)
  • Interview with Dr. Justine Cohen (05:48)
  • Clinical Correlation (26:25)

This week in Oncology

FDA approves rivaroxaban for VTE prevention in hospitalized, acutely ill patients
by Lucas Franki

FDA approval for the new indication is based on results from the phase 3 MAGELLAN and MARINER trials, which included more than 20,000 hospitalized, acutely ill patients.

Therapies for melanoma

  • Classes of therapies for adjuvant melanoma include immune checkpoint inhibitors and targeted therapies.
  • Historically, high-dose interferon was the only available therapy for melanoma. This was associated with a lot of toxicities, without great benefits in terms of overall survival.
  • About 50% of melanomas are BRAF mutated and amendable to adjuvant treatment with the combination of BRAF/MEK inhibitors.
    • Immunotherapy can be used in BRAF mutated patients or BRAF wild type (no mutation).
  • Ipilimumab (anti-CTLA4) demonstrated recurrence-free survival benefit and an overall survival benefit.
    • Toxicity = grade 3 or grade 4 immune-related side effects.
  • Nivolumab and pembrolizumab (anti-PD1) have taken the place of ipilimumab.
    • They are associated with lower rates of toxicities (14%-15%).
  • Side effects of immunotherapy: “itis” (fever, ocular toxicity, lung, colon, rash, many others). These side effects may persist despite cessation of immunotherapy unlike targeted therapies, in which side effects resolve after stopping.
  • Treatment decisions following adverse events depend on how much therapy is delivered prior to the event and the severity of toxicity.

Drug

Class

Mechanism of action

Interferon

Antiviral

· Inhibits protein synthesis

· Inactivates viral RNA

· Enhances phagocytic and cytotoxic mechanisms

Ipilimumab

Checkpoint inhibitor

· IgG1 monoclonal antibody against cytotoxic T-lymphocyte antigen 4

Nivolumab

Checkpoint inhibitor

· Human IgG4 monoclonal antibody against programmed death 1 (PD-1)

Pembrolizumab

Checkpoint inhibitor

· Human IgG4 monoclonal antibody against programmed death 1 (PD-1)

Dabrafenib

Targeted therapy

· BRAF inhibitor

Vemurafenib

Targeted therapy

· BRAF inhibitor

Trametinib

Targeted therapy

· MEK inhibitor

Show notes by Emily Bryer, DO, resident in the department of internal medicine, University of Pennsylvania, Philadelphia.

References

Weber J et al. Adjuvant nivolumab versus ipilimumab in resected stage III or IV melanoma. N Engl J Med. 2017;377:1824-35.

Eggermont AMM et al. Adjuvant pembrolizumab versus placebo in resected stage III melanoma. N Engl J Med. 2018;378:1789-1801.

Long GV et al. Adjuvant dabrafenib plus trametinib in stage III BRAF-mutated melanoma. N Engl J Med. 2017;377:1813-23.

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Ilana Yurkiewicz on Twitter: @ilanayurkiewicz

Podcast Participants

David Henry, MD
David Henry, MD, FACP, is a clinical professor of medicine at the University of Pennsylvania and vice chairman of the department of medicine at Pennsylvania Hospital in Philadelphia. He received his bachelor’s degree from Princeton University and his MD from the University of Pennsylvania, then completed his internship, residency, and fellowship at the Hospital of the University of Pennsylvania. After 2 years as an attending in the U.S. Air Force, he was drawn to practicing as a hem-onc because of the close patient contact and interaction, and his belief that, win or lose with each patient, one can always make a difference in their care and lives. Follow Dr. Henry on Twitter: @davidhenrymd.
Ilana Yurkiewicz, MD
Ilana Yurkiewicz, MD, is a fellow in hematology and oncology at Stanford University, where she also completed her internal medicine residency. Dr. Yurkiewicz holds an MD from Harvard Medical School and a BS from Yale University. She went into hematology and oncology because of the high-stakes decision-making, meaningful relationships with patients, and opportunity to help people through some of the toughest challenges of their lives. Dr. Yurkiewicz is also a medical journalist. She is a former AAAS Mass Media Fellow and Scientific American blog columnist, and her writing has appeared in numerous media outlets including Hematology News, where she writes the monthly column Hard Questions. Dr. Yurkiewicz is on Twitter: @ilanayurkiewicz.