PracticalDermatology

FDA Approves First Treatment for Rare Form of Skin Cancer

The FDA granted accelerated approval to Bavencio (avelumab) for the treatment of adults and pediatric patients 12 years and older with metastatic Merkel cell carcinoma (MCC), including those who have not received prior chemotherapy. This is the first FDA-approved treatment for metastatic MCC, a rare, aggressive form of skin cancer.

Bavencio targets the PD-1/PD-L1 pathway (proteins found on the body’s immune cells and some cancer cells). By blocking these interactions, Bavencio may help the body’s immune system attack cancer cells.

Bavencio received an Accelerated Approval, which enables the FDA to approve drugs for serious conditions to fill an unmet medical need using clinical trial data that is thought to predict a clinical benefit to patients. Further clinical trials are required to confirm Bavencio’s clinical benefit and the sponsor is currently conducting these studies.

Approval of Bavencio was based on data from a single-arm trial of 88 patients with metastatic MCC who had been previously treated with at least one prior chemotherapy regimen. The trial measured the percentage of patients who experienced complete or partial shrinkage of their tumors (overall response rate) and, for patients with a response, the length of time the tumor was controlled (duration of response). Of the 88 patients who received Bavencio in the trial, 33 percent experienced complete or partial shrinkage of their tumors. The response lasted for more than six months in 86 percent of responding patients and more than 12 months in 45 percent of responding patients.

Common side effects of Bavencio include fatigue, musculoskeletal pain, diarrhea, nausea, infusion-related reactions, rash, decreased appetite and peripheral edema. The most common serious risks of Bavencio are immune-mediated, where the body’s immune system attacks healthy cells or organs, such as the lungs (pneumonitis), liver (hepatitis), colon (colitis), hormone-producing glands (endocrinopathies) and kidneys (nephritis). In addition, there is a risk of serious infusion-related reactions. Patients who experience severe or life-threatening infusion-related reactions should stop using Bavencio. Women who are pregnant or breastfeeding should not take Bavencio because it may cause harm to a developing fetus or a newborn baby.

Pierre Fabre and Hill Dermaceuticals Partner in Commercial Partnership for Tolak for AKs

Pierre Fabre Dermo-Cosmetique and Hill Dermaceuticals, Inc. have entered into a strategic commercial partnership for Tolak, a patented prescription dermatologic drug, indicated for the topical treatment of actinic keratosis lesions of the face, ears, and/or scalp.

By the Numbers

Percentage of subjects who were more sunburned with SPF 50+ than with SPF 100+ sunscreen in a real-world, split-face comparison study supported by Johnson & Johnson and presented at the Annual Meeting of the AAD last month (Poster 4839).

Subjects—skiers in Vail, CO—were furnished with both SPF 50+ and SPF 100+ formulations (but blinded to the product identities) and randomized to apply each product to either the right or left side of the face. Subjects were instructed to use the sunscreens as they would normally during ski activities, using diaries to record sun exposure time and frequency and timing of sunscreen reapplications. Subjects reported the next morning for clinical evaluation.

After an average duration of sun exposure for all subjects of 6.05±1.29 hours, only five percent of subjects were more sunburned on the SPF 100+ side. Clinical grading showed subjects had a two-fold increase in erythema on the SPF 50+ side, compared with the SPF 100+ side.

There were no differences in the amount of sunscreen used or in the frequency of reapplications for the formulations.

Under the terms of the agreement, Pierre Fabre Dermo-Cosmétique will be granted an exclusive license for Tolak in a broad territory through two of its subsidiaries: Pierre Fabre USA for the immediate distribution of Tolak in the US, and Pierre Fabre for commercialization in certain other countries (pending local authorization). Pierre Fabre has also acquired the option rights to countries outside the initial licensed territory. Hill Dermaceuticals will retain ownership of the NDA for Tolak in the US and will supply the product to Pierre Fabre on an exclusive basis. Pierre Fabre Dermatologie will be responsible for obtaining marketing authorizations outside the US and will hold marketing approvals in other countries.

New Biomarker May Help Guide Metastatic Melanoma Treatment

Measuring levels of Bim—a protein made by cancer-fighting T cells—via a simple blood draw can help doctors predict which metastatic melanoma patients would benefit from anti-PD-1 checkpoint blockade.

Haidong Dong, MD, PhD, currently a Cancer Research Institute CLIP investigator, and Svetomir Markovic, MD, PhD, who was a CRI clinical investigator from 2002-2007, both at Mayo Clinic in Rochester, MN, published their findings in the Journal of Clinical Investigation.

Drs. Dong and Markovic showed that patients who experienced clinical benefit had higher levels of Bim before treatment compared to patients who experienced tumor growth.

By monitoring Bim levels after treatment, doctors could determine if the immunotherapy was working. Compared to non-responders, Bim levels in responders decreased significantly after the first three months of treatment, the study showed. Bim measurements could signal successful anti-tumor immune responses (or lack thereof) even earlier than traditional assessment tools, including radiographic imaging. Bim measurements also provided clinicians with clarity concerning the challenge of pseudoprogression, in which a tumor can appear “to get worse before it gets better.”

This is important for two reasons, the study authors note. First, it could help ensure that patients who are experiencing pseudoprogression but are still responding aren’t prematurely taken off the treatment. Second, it could help prevent patients who aren’t responding from being subjected to further doses and potential side effects, and allow them to seek out other treatment options.

High Bim levels mean that the tumor is protecting itself from the immune system via PD-1/PD-L1 activity; decreased levels of Bim biomarkers during treatment would suggest the interaction between PD-1 and PD-L1 in tumor-reactive T cell populations is successfully blocked.

Skin Cancer Finding Provides Hope for Patients with Rare Type of Melanoma

A team of researchers report a significant genetic association linked to an aggressive form of melanoma in a study published in the journal Genome Research. Led by investigators at the Translational Genomics Research Institute (TGen), in collaboration with Vanderbilt University Medical Center, Memorial Sloan Kettering Cancer Center, and Mayo Clinic, researchers identified a protein target that opens a window into acral lentiginous melanoma (ALM), may aid in diagnosis and, one day, lead to improved treatments.

The researchers sequenced samples from 34 patients with ALM and found significant evidence that inhibiting a protein called TERT may be “an effective approach” to destroying ALM cells. In laboratory experiments, more than 75 percent of ALM cancer cells were affected, following 72 hours of exposure to a drug that inhibits TERT.

“These data establish a foundation for understanding ALM’s genetic triggers, with the ultimate goal to inform ALM clinical management for patients,” said Dr. Jeffrey Sosman, an internationally recognized melanoma expert and another of the paper’s co-senior authors.

“Our analysis of these patients confirms a number of findings of prior smaller analyses, but also sheds new light on the molecular foundations of human acral melanoma,” said Dr. Charlotte Ariyan, the third co-senior author of the study. Dr. Ariyan is a surgeon specializing in melanoma at Memorial Sloan Kettering Cancer Center.

“Mapping the relatively uncharted landscapes of melanoma in non-cutaneous parts of the body will have broad relevance for understanding melanoma biology and clinical management similar to cutaneous melanoma,” said Dr. Aleksandar Sekulic, a skin cancer expert who holds joint appointments at TGen and Mayo Clinic, and a co-author of the study.

Genetic changes in TERT were found among 41 percent of the patients in this study, which also suggests that additional research should be undertaken to verify the impact of genetic aberrations on TERT activity.

“Based on our findings of TERT alterations in nearly half of the patient samples we analyzed, TERT inhibitors represent a putative therapeutic strategy in ALM,” said Dr. Winnie Liang, an Assistant Professor and Director of TGen’s Collaborative Sequencing Center, and the study’s lead author.