Emerging therapies are changing the landscape of melanoma treatment

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Specialist pharmacists play a key role in supporting treatment adherence.

Although melanoma accounts for about 1% of skin cancer diagnoses, it is responsible for a large portion of the lives lost to the disease, with about 8,000 deaths expected in the United States in 2022.1 A
The main reason for the high morbidity rate is that melanoma is much more likely to metastasize than other skin cancers.

Despite the high morbidity rate of melanoma, the disease accounts for only 5.6% of all new cancer cases in the United States, with the incidence of melanoma increasing steadily for several decades.1 Based on this statistic, the American Cancer Society estimates that 100,000 new melanoma diagnoses will occur in the United States in 2022.2

Current treatments
The exact cause of malignant melanoma is unknown, but it is thought to be related to excessive UV exposure from the sun and tanning beds. As such, most melanomas are highly preventable with limited UV exposure, use of sunscreen, and education about risk factors and warning signs. When detected before it begins to spread, melanoma also has a 99% 5-year survival rate.3

In addition, surgical resection is often an effective therapy for most patients with early identified melanoma. In more advanced stages, such as metastatic melanoma, patients have always been treated with standard cancer treatments such as radiation therapy and chemotherapy.1.2

Approved by the FDA in 1998, high-dose IL-2 was the first immunotherapy for metastatic melanoma. However, the potential for serious toxicities from IL-2 treatment has resulted in the development of new products with fewer toxic effects. Additionally, the landscape for treating metastatic melanoma has changed dramatically during recent advances in targeted therapies, and immunotherapy (eg, checkpoint inhibitors) has been shown to be more effective than chemotherapy.2.4

Targeted therapy products work by directly treating melanoma cells, with treatment targets often including mutated genes or proteins involved in regulating cell growth and division. Upon mutation, these cells grow and multiply at an uncontrollable rate, with the most common mutation being in the BRAF embarrassed.1

About 50% of all melanomas have a BRAF gene mutation. When this happens, the MEK The gene (and the encoded MEK protein) interacts with BRAF proteins helping in cell growth.1

Drugs targeting MEK protein inhibition are a common therapy for patients with malignant melanoma and BRAF mutations. Targeted therapies for inhibition of BRAF and/or MEK proteins include binimetinib (Mektovi;
Pfizer), encorafenib (Braftovi; Pfizer), dabrafenib (Tafinlar; Novartis), trametinib (Mekinist; Novartis), vemurafenib (Zelboraf; Genentech) and cobimetinib (Cotellic; Genentech). Additionally, the combination of a BRAF inhibitor and an MEK inhibitor is a common approach in treating a patient with a BRAF mutation who needs targeted therapy, as the combination often works better than monotherapy.1,2,4

Progress has been made with immune checkpoint inhibitors, now a mainstay in the treatment of advanced melanoma. Unlike targeted therapies, which attack melanoma cells directly, immunotherapy aims to improve the immune system’s ability to identify and destroy melanoma cells. The PD-1 inhibitors pembrolizumab (Keytruda; Merck) and nivolumab (Opdivo; Bristol Myers Squibb) and the CTLA-4 inhibitor ipilimumab (Yervoy; Bristol Myers Squibb) are included in this class of drugs. These drugs actively block proteins involved in decreasing T-cell identification and killing melanoma cells. Additionally, blocking these proteins allows T cells to more effectively attack melanoma cells on their own. Other immunotherapies such as melanoma vaccines and cell therapy using tumour-infiltrating lymphocytes are also being explored.1,2,4

Updates in the treatment of melanoma
Effective immunotherapy options for the treatment of advanced melanoma include ipilimumab/nivolumab, PD-1 inhibitor monotherapy, and more recently the fixed-dose relatlimab/nivolumab combination. On March 18, 2022, the FDA approved nivolumab and relatlimabrmbw (Opdualag; Bristol Myers Squibb) for the treatment of adult and pediatric patients 12 years of age and older with unresectable or metastatic melanoma. Nivolumab and relatlimab-rmbw is a combination immunotherapy treatment of nivolumab, a PD-1 inhibitor, with the new LAG-3 blocking antibody, relatlimab, the combination of which has been shown to increase the activation of T lymphocytes.4

FDA approval of nivolumab and relatlimabrmbw was based on data from the Phase 2/3 RELATIVITY-047 trial (NCT03470922) in which nivolumab and relatlimab-rmbw more than doubled median progression-free survival per compared to nivolumab monotherapy, at 10.1 months versus 4.6 months. , respectively. No new safety events were identified with nivolumab and relatlimab-rmbw compared to nivolumab alone.4.5

When used as treatment, nivolumab and relatlimabrmbw are given as an intravenous infusion over 30 minutes every 4 weeks or until disease progression. However, new and emerging treatments often come with a heavy financial burden, and nivolumab and relatlimab-rmbw continue this trend at a single infusion wholesale acquisition cost of $27,389 with an annual price of $328 $668.1,5,6

Role of the specialist pharmacist
The specialty pharmacist is a key member of any patient’s healthcare team. They can provide patients and caregivers with medication and disease-specific education before and throughout treatment. They play a major role in monitoring and managing adverse reactions (AEs), as well as supporting adherence to treatment.

Early recognition and control of AEs can help prevent unnecessary discontinuation of medication, thereby improving patient outcomes. Specialty pharmacists can also collaborate and facilitate communication between other segments of the healthcare team, such as dermatology and oncology, for the treatment of advanced melanoma.

References
1. Review of a new drug: Opdualag. IPD analysis. Accessed June 16, 2022. https://www.ipdanalytics.com/
2. Melanoma skin cancer. American Cancer Society. Accessed June 16, 2022. https://www.cancer.org/cancer/melanoma-skin-cancer.html
3. Skin cancer facts and statistics. Skin Cancer Foundation. May 2022. Accessed July 25, 2022. https://www.skincancer.org/skin-cancer information/skin-cancer-facts/
4. Oncology: melanoma. IPD analysis. Accessed June 16, 2022. https://www. ipdanalytics.com/
5. Fecher LA. Considerations for first-line metastatic melanoma: which treatment is best? ASCO Daily News. April 13, 2022. Accessed June 16, 2022. https://dailynews.ascopubs.org/do/10.1200/ADN.22.200895/full/?utm_source=TrendMD&utm_medium=cpc&utm_campaign=ASCO_Daily_Nes_TrendMD_0
6. The United States Food and Drug Administration approves the first LAG-3 blocking antibody
combination, Opdualag (nivolumab and relatlimab-rmbw), as a treatment for patients with unresectable or metastatic melanoma. Press release. Bristol Myers Squibb. March 18, 2022. Accessed June 16, 2022. https://www.businesswire.com/news/home/20220304005561/en

About the Author
Marcie Morris, PharmD, CSP, is Clinical Program Manager at AllianceRx Walgreens Pharmacy.

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