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UCLA Researcher Provides Insight Into the Impact of Pembrolizumab in Melanoma

Andrew J. Roth
Published: Saturday, Sep 13, 2014

John Glaspy, MD, MPH

John Glaspy, MD, MPH

Last week, the FDA approved pembrolizumab (Keytruda) for the treatment of patients with advanced or unresectable melanoma following progression on prior therapies. In the pivotal KEYNOTE-001 study, at the recommended dose for pembrolizumab of 2 mg/kg, the overall response rate was 24%, with a response duration lasting from 1.4 to 8.5 months.

Pembrolizumab is the first PD-1 inhibitor and sixth new melanoma treatment to gain approval since 2011.

To gain further insight into the approval of this novel agent, OncLive interviewed John Glaspy, MD, MPH, from the Jonsson Comprehensive Cancer Center and UCLA, where research into pembrolizumab was conducted.

Could you discuss the KEYNOTE study results and the approval of pembrolizumab?

Pembrolizumab was approved because it is active for the treatment of metastatic melanoma and brings something new to the table in terms of working in patients who have had all the benefit from the other available medications. About half of melanomas have a BRAF mutation. Pembrolizumab works equally well in patients with this mutation as it does in patients who are BRAF-negative who have fewer therapeutic options.

Pembrolizumab is the 6th drug to gain approval in melanoma since 2011. What is the impact of this drug on the treatment of melanoma?

This drug is up at the top of the new drugs for melanoma for a couple of reasons. First, pembrolizumab can be used in BRAF-negative and BRAF-positive tumors. Second, it works when the other drugs have stopped working or failed to work altogether. Third, when it works, it tends to work for a very long time. These immune checkpoint inhibitors are more durable in their responses than BRAF inhibitors. I would put pembrolizumab in the top rung of those new drugs that have been approved.

Pembrolizumab is the first PD-1 inhibitor to gain approval in the US. What will be the impact on immunotherapy as a whole?

I think this drug will soon find community use in not just melanoma but in non-small cell lung cancer, the most common kind of lung cancer. It will find use in other cancers as well. This drug is also going to be looked at in combinations with other immune strategies and immune vaccines. As this approach, checkpoint inhibition, facilitates the continuation of an immune reaction when it otherwise might stop, treatments good at starting an immune reaction, like vaccines, need to be studied in combination with checkpoint inhibitors. Using checkpoint inhibitors in the adjuvant setting and in combination with one another will also need to be evaluated.

Immunotherapy clearly is going to be an important part of oncology. We are going to be working out how to integrate immunotherapies with all the other approaches to cancer treatment both in melanoma and other cancers.

What side effects are important for a community oncologist to consider with a PD-1 inhibitor?

All their toxicities are related to their intended effect on the immune system. If the immune system has brakes, they are there for a reason. These brakes have evolved to help to make sure that the immune system is under control and does not attack normal cells.

With anti-PD drugs, we have seen autoimmunity that can be anywhere, but most commonly in the lungs, where some pneumonitis or inflammation develops. An oncologist must watch for these events and treat with drugs aimed to train the immune system to back off.

That said, these drugs are very well tolerated compared to other cancer therapies. The chance of having a significant immune attack is about 15%, which is manageable, given that melanoma poses a 100% risk to the patient.




View Conference Coverage
Online CME Activities
TitleExpiration DateCME Credits
Medical Crossfire®: Evolving Roles for Targeted Melanoma Therapies: Assessing Rapid Progress in the Field and Looking Toward Future CombinationsFeb 28, 20191.5
Advances in™ Melanoma: Exploring BRAF/MEK in Adjuvant and Neoadjuvant SettingsSep 28, 20191.5
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