Specialist pharmacists play a crucial role in supporting adherence.
While melanoma accounts for about 1% of skin cancer diagnoses, it is responsible for a large proportion of lives lost to the disease, with about 8,000 deaths expected in the United States by 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 is responsible for only 5.6% of all new cancer cases in the United States, with the incidence of melanoma steadily increasing over decades.1 Based on this statistic, the American Cancer Society estimates there will be 100,000 new melanoma diagnoses in the United States by 2022.2
The exact cause of malignant melanoma is unknown, but it is believed to be related to excessive UV exposure from the sun and tanning beds. As such, most melanomas are highly preventable through limited UV exposure, sunscreen use, and education about risk factors and warning signs. When detected before it starts to spread, melanoma also has a 5-year survival rate of 99%.3
In addition, surgical resection is often a successful therapy for most patients with melanoma identified early. In more advanced stages, such as metastatic melanoma, patients have historically been treated with standard cancer treatments such as radiation 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 led to the development of newer products with less toxic effects. Furthermore, the treatment landscape of metastatic melanoma has been vastly changed by recent advances in targeted therapies and immunotherapy (e.g., checkpoint inhibitors) are more effective than chemotherapy.2.4
Targeted therapy products work by directly treating melanoma cells, with treatment targets often containing mutated genes or proteins involved in the regulation of cellular growth and division. After mutation, these cells grow and multiply at an uncontrollable rate, with the most common mutation occurring in the BRAF gene.1
About 50% of all melanomas have a mutation in the BRAF gene. When this happens, the MEK gene (and encoded MEK protein) interacts with the BRAF proteins that aid in cell growth.1
Drugs targeting the inhibition of MEK proteins are a common therapy for patients with malignant melanoma and BRAF mutations. Targeted therapies for inhibition of the 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). In addition, combining a BRAF inhibitor and a MEK inhibitor is a common approach in treating a patient with a BRAF mutation in need of targeted therapy because the combination often works better than monotherapy.1,2,4
Advances have been made with immune checkpoint inhibitors, now a mainstay of treatment for advanced melanoma. Unlike targeted therapies, which target melanoma cells directly, immunotherapy aims to improve the immune system’s ability to identify and destroy melanoma cells. PD-1 inhibitors pembrolizumab (Keytruda; Merck) and nivolumab (Opdivo; Bristol Myers Squibb) and CTLA-4 inhibitor ipilimumab (Yervoy; Bristol Myers Squibb) are included in this class of drugs. These drugs actively block proteins involved in reducing T cell identification and destruction of melanoma cells. Furthermore, blocking these proteins allows T cells to attack melanoma cells themselves more effectively. Additional immunotherapies such as melanoma vaccines and cell therapy using tumor-infiltrating lymphocytes are also being studied.1,2,4
Updates in Melanoma Treatment
Effective immunotherapy options for the treatment of advanced melanoma include combination ipilimumab/nivolumab, PD-1 inhibitor monotherapy and most recently a fixed dose combination of relatlimab/nivolumab. 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 the PD-1 inhibitor nivolumab with the novel LAG-3 blocking antibody relatlimab, the combination of which has been shown to increase T-cell activation.4
The FDA approval of nivolumab and relatlimabrmbw was based on data from the phase 2/3 RELATIVITY-047 study (NCT03470922) in which nivolumab and relatlimab-rmbw more than doubled median progression-free survival compared to nivolumab monotherapy, at 10.1 months versus 4.6 months, respectively. No new safety incidents were identified with nivolumab and relatlimab-rmbw compared to nivolumab alone.4.5
When used in treatment, nivolumab and relatlimabrmbw are given as a 30-minute intravenous infusion every 4 weeks or until disease progression. However, new and emerging treatments often come with a significant financial burden, and nivolumab and relatlimab-rmbw continue this trend at a wholesale purchase price of $27,389 for one infusion with an annual price tag of $328,668.1,5,6
Role of specialty pharmacist
The specialist pharmacist is an important member of each patient’s care team. They can provide patients and caregivers with medication and disease-specific education before and during therapy. They play an important role in the monitoring and management of adverse events (AE) and support adherence.
Early recognition and management of side effects can help to avoid unnecessary medication interruptions, improving patient outcomes. Specialist 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.
1. New Drug Review: 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. Facts and Statistics About Skin Cancer. 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 in 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. US Food and Drug Administration Approves First LAG-3 Blocking Antibody
combination, Opdualag (nivolumab and relatlimab-rmbw), as a treatment for patients with unresectable or metastatic melanoma. news item. Bristol Myers Squibb. March 18, 2022. Accessed June 16, 2022. https://www.businesswire.com/news/home/20220304005561/en
About the author
Marcie Morris, Pharm D, CSP, is a clinical program manager at AllianceRx Walgreens Pharmacy.