Elevate Cutaneous Oncology

Skin cancer and actinic keratoses (AKs) are some of the most common conditions seen in dermatology, and their global prevalence is on the rise.¹ New drugs and treatment approaches are redefining strategies for cutaneous oncology. Speaking at Maui Derm NP + PA 2022, Ted Rosen, MD, and George Martin, MD, drilled down on the latest solutions for tackling the challenges of the skin pre-cancers and cancers.²

The presentation began with an update on the management of actinic keratosis (AK). Rosen and Martin reviewe the recent American Academy of Dermatology (AAD) treatment guidelines. They highlighted key take-aways such as recommendations on UV protection, cryosurgery, imiquimod, and flououracil (5-FU).

The speakers also delved into newest topical therapy for AKs. The focus of a recent AAD update which provided a strong recommendation, tirbanibulin 1% ointment (Klysiri; Almirall) achieved a median AK clearance of 87.5% in phase 3 trials and only requires a 5 day course of treatment, the speakers noted.³

Martin remarked on this development, “Tirbanibulin 1% ointment has become our new ‘go to’ first-line therapy in the treatment of actinic keratoses. The convenience of a 5-day, once daily application and minimal side effects has led to really good compliance and a patient willingness to do additional courses of therapy particularly for facial AK.”

However, He added this caution, “Tirbanibulin is absorbed and we have to be careful of women of childbearing years so we take precautions in much the same way we treat these patients with 5-FU”.

Rosen and Martin then offered tips for optimizing efficacy and minimizing pain during photodynamic therapy (PDT). They discussed multiple studies on pain associated with PDT treatment and detailed ways to conduct painless PDT.

“The painless PDT protocol has evolved to become the only way we employ 5-aminolevulinic acid photodynamic therapy (ALA-PDT),” Martin said. “Simultaneous application of ALA and illumination for 30 minutes has equal efficacy as 45 and 60 minutes simultaneous application and illumination protocols for both face and scalp. More importantly it has almost no pain associated with the protocol when compared to the standard ALA PDT protocol which utilizes 1-hour incubation periods followed by illumination”. Recently, it has been shown that the addition of 10,000 units of vitamin D taken daily for up to two weeks prior to PDT, significantly enhances efficacy.

Use of PDT to treat squamous cell carcinoma continue to evolve. A recent retrospective study of ALA-PDT for squamous cell carcinoma in situ performed by Kibbi et. al. demonstrated an outstanding response in tumors on the face (86.8%) compared to the trunk/extremities (66.7%). Moreover, ALA incubation of 3 hours or longer produced better clearance rates and smaller lesions under 2 cm responded better than larger lesions.“⁴

While off label, this therapy is highly effective and reduces the incidence of scarring associated with surgery and other destructive modalities such as ED&C and is also very safe,” Martin said. He added, “Superficial basal cell carcinoma also responds very well to ALA-PDT using a similar protocol but both treatments are technically off-label”.

The second part of the presentation focused on the treatment of advanced squamous cell and basal cell carcinoma. A recent addition to the armamentarium is cemiplimab (Libtayo; Sanofi and Regeneron Pharmaceuticals), a PD-1 immune check point inhibitor, which was FDA-approved in early 2021 fotreatment of locally advanced and metastatic basal cell carcinoma. Candidates for this therapy include those who have failed surgery or radiation and for whom hedgehog inhibitors are not appropriate. Clinical trial data demonstrated disease control was attained in 68% of patients with metastatic disease and an 80% of those with locally advanced basal cell carcinoma.⁵ This medication had a previous approval for the treatment of advanced cutaneous squamous cell carcinoma where the disease control rate was 72%.

The presentation ended with an update on therapies for patients who have failed immunotherapies.Cavrotolimod, an intra-tumor injectable therapy, is now being studied in squamous cell carcinoma and Merkel cell carcinoma. It employs a novel “spherical nucleus acid” technology utilizing a lipid nano particle core. The mechanism of action is one of immune stimulation by the incorporation of a Toll-like 9 receptor agonist. Commenting on this pipeline therapy, Martin stated, “it has proven effective in treating PD-1 refractory cutaneous metastatic melanoma.” It will be exciting to see more data from this medication, and others like it, in the future”.

References:

1. Christenson LJ, Borrowman TA, Vachon CM, et al. Incidence of basal cell and squamous cell carcinomas in a population younger than 40 years. JAMA. 2005;294(6):681-690. doi:10.1001/jama.294.6.681

2. Martin G, Rosen T. Cutaneous oncology update 2022. Presented at Maui Derm NP + PA 2022. HeldJune 23 -25, 2022, Colorado Springs, Colorado, and virtual.

3. Bullock TA, Negrey J, Hu B, Warren CB, Hasan T, Maytin EV. Significant improvement of facial actinic keratoses after blue light photodynamic therapy with oral vitamin D pretreatment: An interventional cohort-controlled trial. Journal of the American Academy of Dermatology. 2022;87(1):80-86. doi:10.1016/j.jaad.2022.02.067

4. Kibbi N, Zhang Y, Leffell DJ, Christensen SR. Photodynamic therapy for cutaneous squamous cell carcinoma in situ: Impact of anatomic location, tumor diameter, and incubation time on effectiveness. J Am Acad Dermatol. 2020;82(5):1124-1130. doi:10.1016/j.jaad.2019.10.079

5. Stratigos AJ, Sekulic A, Peris K, et al. Cemiplimab in locally advanced basal cell carcinoma after hedgehog inhibitor therapy: an open-label, multi-centre, single-arm, phase 2 trial. The Lancet Oncology. 2021;22(6):848-857. doi:10.1016/S1470-2045(21)00126-1