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 correl