An interview with Dr. Pauline Funchain from Cleveland Clinic in Cleveland, OH, author on "Systemic Therapy for Melanoma: ASCO Guideline Rapid Recommendation Update." Dr. Funchain reviews recent evidence and updated recommendations from the ASCO Expert Panel for the use of tebentafusp in patients with metastatic uveal melanoma. For more information, visit www.asco.org/melanoma-guidelines.

TRANSCRIPT

Brittany Harvey: Hello and welcome to the ASCO Guidelines podcast series brought to you by the ASCO Podcast Network, a collection of nine programs covering a range of educational and scientific content and offering enriching insight into the world of cancer care. You can find all the shows, including this one at asco.org/podcasts.

My name is Brittany Harvey and today I am interviewing Dr. Pauline Funchain from Cleveland Clinic in Cleveland, Ohio, author on Systemic Therapy for Melanoma: ASCO Guideline Rapid Recommendation Update. Thank you for being here, Dr. Funchain.

Dr. Pauline Funchain: It's great to be here with you, Brittany. Thank you!

Brittany Harvey: First, I'd like to note that ASCO takes great care in the development of its guidelines and ensuring that the ASCO conflict of interest policy is followed for each guideline.

The full conflict of interest information for this guideline panel is available online with the publication of the guideline in the Journal of Clinical Oncology.

Dr. Funchain, do you have any relevant disclosures that are directly related to this guideline topic?

Dr. Pauline Funchain: I do not have relevant disclosures that relate to this guideline topic.

Brittany Harvey: Great, thank you. Then getting into the rapid update, what prompted this rapid update to the Systemic Therapy for Melanoma: ASCO Guideline published in 2020?

Dr. Pauline: So, earlier this year, on January 25th, the FDA approved tebentafusp for metastatic uveal melanoma. So, this is the first FDA approval for metastatic uveal melanoma. We felt it was really important to put out a rapid update to let both clinicians know about the therapy and also so that more patients can get access to it as quickly as possible.

Brittany Harvey: Understood. So, then based on this new FDA approval, what are the updated recommendations for patients with uveal melanoma?

Dr. Pauline Funchain: So, any patients who have a previously untreated metastatic uveal melanoma, and also who are HLA-A*02:01 positive, this group of patients should be offered tebentafusp as systemic therapy.

This is the only systemic therapy that has been shown to prolong overall survival in patients with metastatic uveal melanoma. And if you look at the kind of benefit that was seen, patients who were on tebentafusp had a median overall survival of 21.7 months versus 16 months in comparison to investigator's choice. In this case, that was either single agent pembrolizumab, ipilimumab, or dacarbazine. So, it is a pretty significant overall survival benefit.

Brittany Harvey: Great! Thank you for reviewing those updated recommendations and the data behind them. So, what should clinicians know as they implement this updated recommendation?

Dr. Pauline Funchain: So, they should know that there was a great overall survival benefit seen, but it doesn't correlate with the objective response rate that was seen in the trial. So, for patients who were treated with tebentafusp, the objective response rate was 9%. And for those patients who were treated with the investigator's choice, again, that was single agent pembrolizumab, ipilimumab, or dacarbazine, the response rate was 5%.

So, that margin was not very different in terms of objective response rate when looking at RECIST-based criteria, so radiologic criteria for response, but the survival was clearly seen. And interestingly, even in those patients that had radiologic progression, there was an improved survival for those patients who were on tebentafusp versus investigator's choice.

So, there is some kind of survival benefit that may not correlate with what is seen on imaging. So, clinicians should know that they may not see a dramatic response in terms of tumor size on imaging, but patients may still benefit from the therapy.

Brittany Harvey: Understood. So, then you've just talked a little bit about responses in patients. So, how does this guideline update affect patients with melanoma?

Dr. Pauline Funchain: So, despite a difference in response rate, long story short, there is an overall survival difference. So, really, this is the first overall survival difference that we have seen in metastatic uveal melanoma.

It is really exciting. It is finally an approved drug for metastatic uveal melanoma, which did not have any approved or standard of care, systemic drugs. So, this is a really big win for a rare disease. I think, in terms of the general melanoma field and also the cancer field in general, this is really an exciting first-in-class drug on two different fronts. It is the first approved T-cell receptor therapy. It is also the first bispecific protein and it works differently than other immunotherapies we have seen. So, hopefully, this is something we see more of in other cancers.

Brittany Harvey: Definitely, it's good to see that these patients finally have an option and we'll look forward to research in other cancers as well. So, then finally, Dr. Funchain, what are the outstanding questions regarding systemic therapy for melanoma?

Dr. Pauline Funchain: Well, there are multiple questions that are outstanding. I think, for metastatic uveal melanoma, I think there are a lot of questions about the dissociation between the radiologic response and survival. I think there are questions about knowing when to stop tebentafusp if it's not working because we don't really have a good sense of what we should be using to know if this is not the right therapy for that patient.

I think we would love to know what the biomarkers of response are, and we may need different ways of looking for how to judge if a patient is benefiting from tebentafusp and other systemic therapies. And I think that there's still a big question in uveal melanoma about whether we start with systemic therapy or local therapy. I don't think that's been answered.

Now, in terms of the entire guideline, I think for melanoma in general, there are new data that are emerging and have been recently published and we will be looking forward to the next ASCO guideline in systemic therapy for melanoma because I think that there are a lot of emerging data that need to be addressed.

Brittany Harvey: Definitely. We'll look forward to that new research in uveal melanoma and to reviewing the updated data with the guideline panel for the next edition of the systemic therapy for melanoma guideline. So, I want to thank you so much for your work to rapidly updating this guideline, and thank you for your time today, Dr. Funchain.

Dr. Pauline Funchain: Thank you for having me. It is really meaningful to us to be able to offer education and get the word out about therapies that can help our patients.

Brittany Harvey: Agreed. And thank you to all of our listeners for tuning in to the ASCO Guidelines Podcast series. To read the full rapid recommendation update, go to www.asco.org/melanoma-guidelines.

You can also find many of our guidelines and interactive resources in the free ASCO Guidelines app available on iTunes or the Google Play Store. If you have enjoyed what you've heard today, please rate and review the podcast and be sure to subscribe so you never miss an episode.

The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions.

Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.

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