I look forward to sharing more during my presentation “What’s New in the Management of Advanced Skin Cancer,” but here is quick preview of what to expect and to prepare for. Despite the last decade’s revolution of skin cancer treatment paradigms, global non-melanoma skin cancer (NMSC) and melanoma age-standardized incidence ratios remain elevated at 79.1 and 3.6 per 100,000 persons and they contribute to an estimated 62,800 and 56,100 deaths annually, respectively. Very recently, several novel therapies have been approved for the treatment of advanced NMSC and show promise for patients who are not surgical candidates. Many off-label trials are also underway.
Hedgehog pathway inhibitors (HHI) have been mainstay therapy for non-surgical basal cell carcinoma (BCC) patients since first-in-class vismodegib was approved by the FDA in 2012. Yet, resistance and adverse effects remain a paramount concern as their post-market evaluation and study as neoadjuvants continue. We can now look forward to increasing our knowledge and comfort with the use of checkpoint inhibitors in the NMSC therapy arsenal too; cemiplimab, first approved for squamous cell carcinoma (SCC) in 2018, was approved in February 2021 for those with locally advanced and metastatic BCC who previously received HHI or were non-HHI candidates. Of importance, the FDA definition of non-candidacy is not explicit. As of July 2021, locally advanced, recurrent, and metastatic SCC patients were approved for pembrolizumab therapy as well. Numerous in-progress trials for unresectable SCCs using various combinations of cemiplimab, nivolumab, pembroliuzumab, avelumab, panitumumab and talimogene laherparepvec are in progress too.
In contrast, systemic therapy for non-surgical, advanced, or metastatic melanoma patients has not received any FDA approvals since encorafenib and binimetinib in 2018, as highlighted by this month’s timely JAAD excerpt by Skudalski et al. Nonetheless, at the time of this writing, www.clinicaltrials.gov shows 580 active trials for stage III/IV melanoma. Interesting findings regarding artificial intelligence imaging in prognosis determination and microbiome association with idiosyncratic checkpoint inhibitor response will be something to keep an eye on moving forward.
It is my hope that attendees come away from my presentation on “What’s new in the Management of Advanced Skin Cancer” with a greater understanding of the mechanism, efficacy, utility, and risks of the aforementioned HHI and checkpoint inhibitors and, most importantly, more context regarding the patient populations in which they should be considered in or avoided most. As you will come to learn, if you haven’t already, it is extremely important to assess underlying risk factors when deciding on these high-risk treatment options – lesion location, immunosuppression or organ transplantation, pathologic subtype, mutation profile, prior radiotherapy exposure, and anatomic size, to name a few, are all uniquely counterweighted variables to consider. Through this presentation I expect attendees to have much greater familiarity and confidence in this area.
I share these thoughts not only to provide a brief glimpse into what I plan on communicating at this year’s much-anticipated in-person AAD Annual Conference, but also to highlight the continuation of this past decade’s trend of therapeutic innovation. It is reassuring that, even in the midst of this century’ most-challenging health crisis, treatment paradigms of our field’s most fatal adversaries have continued to evolve.
What sessions am I personally looking forward to listening to and sitting in on? I have listed a few from the extensive list of incredible educational content in this year’s program: U008 - OFF-LABEL USE OF BIOLOGICS AND NEW MEDICATIONS; F002 - COMPLEX MEDICAL DERMATOLOGY CASES - PEARLS AND PITFALLS; F005 - DON’T BE AN ONLINE TOOL: #WINNING IN THE AGE OF SOCIAL MEDIA; F020 - THE CHANGING LANDSCAPE OF EARLY-STAGE MELANOMA MANAGEMENT U044 - NOVEL USES FOR LASER & LIGHT-BASED DEVICES IN PEDIATRIC PATIENTS; and U053 - MERKEL CELL CARCINOMA: UPDATES IN PRACTICE MANAGEMENT.
- Global Burden of Disease 2019 Cancer Collaboration, Kocarnik JM, et al. Cancer Incidence, Mortality, Years of Life Lost, Years Lived With Disability, and Disability-Adjusted Life Years for 29 Cancer Groups From 2010 to 2019: A Systematic Analysis for the Global Burden of Disease Study 2019. JAMA Oncol. 2021 Dec 30:e216987. doi: 10.1001/jamaoncol.2021.6987. Epub ahead of print. PMID: 34967848; PMCID: PMC8719276.
- Dercle L, Zhao B, Gönen M, Moskowitz CS, Firas A, Beylergil V, Connors DE, Yang H, Lu L, Fojo T, Carvajal R, Karovic S, Maitland ML, Goldmacher GV, Oxnard GR, Postow MA, Schwartz LH. Early Readout on Overall Survival of Patients With Melanoma Treated With Immunotherapy Using a Novel Imaging Analysis. JAMA Oncol. 2022 Jan 20:e216818. doi: 10.1001/jamaoncol.2021.6818. Epub ahead of print. PMID: 35050320; PMCID: PMC8778619.
- Lee, K.A., Thomas, A.M., Bolte, L.A. et al. Cross-cohort gut microbiome associations with immune checkpoint inhibitor response in advanced melanoma. Nat Med (2022). https://doi.org/10.1038/s41591-022-01695-5
Dr. Schlesinger reports grant funding from several organizations, including Regeneron, Bristol-Meyers Squibb, and Pfizer, is on the advisory board for Amgen. Dr. Synder reports no conflicts of interest.
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