Opdualag (BMS), a fixed-dose combination of two immune checkpoint inhibitors — nivolumab (Opdivo), a programmed death receptor-1 (PD-1) inhibitor, and relatlimab-rmbw, a lymphocyte-activation gene-3 (LAG-3) blocking antibody — has been approved by the FDA for treatment of unresectable or metastatic melanoma in patients ≥12 years old. Relatlimab, which is only available in combination with nivolumab, is the first LAG-3 blocking antibody to become available in the US. Immune checkpoint inhibitors, including the anti-CTLA-4 antibody ipilimumab (Yervoy) and the PD-1 inhibitors nivolumab and pembrolizumab (Keytruda), have been available for several years for treatment of melanoma.

Excessive exposure to ultraviolet (UV) radiation is associated with sunburn, photoaging, and skin cancer. Sunscreens are widely used to reduce these risks, but questions remain about their effectiveness and safety. The FDA has issued a proposed rule that would require manufacturers to perform additional safety studies for some sunscreen active ingredients and would mandate better UVA protection in sunscreen products. Some sunscreen products containing FDA-approved active ingredients are listed in Table 2.

The FDA has required the addition of information about an increased risk of nonmelanoma skin cancer (basal cell carcinoma [BCC] and squamous cell carcinoma [SCC]) to the labels of products containing the diuretic hydrochlorothiazide.

Excessive exposure to ultraviolet (UV) radiation is associated with sunburn, photoaging, and skin cancer. Sunscreens are widely used to reduce these risks, but some questions remain about their effectiveness and safety.

The FDA has approved the fully-human programmed death ligand 1 (PD-L1) blocking antibody avelumab (Bavencio – EMD Serono/Pfizer) for treatment of metastatic Merkel cell carcinoma (MCC) in patients ≥12 years old. Avelumab is the first drug to be approved in the US for this rare skin cancer. About 1600 people in the US, most commonly older adults (mean age at presentation is 75 years), are diagnosed each year with MCC. Most of these patients can be treated with surgical resection, but ~50% will have a recurrence and >30% will eventually have metastatic disease. Median progression-free survival in patients with metastatic disease has been about 3 months with chemotherapy. MCC tumors, which often express PD-L1, have been treated offlabel with the PD-1 inhibitors pembrolizumab (Keytruda)1 and nivolumab (Opdivo).2

In an ongoing single-arm trial (JAVELIN Merkel 200), 88 patients with metastatic MCC (58 with PD-L1 positive tumors, 16 PD-L1 negative, 14 not assessable) who were previously treated with at least one chemotherapy regimen received at least one dose of avelumab; 75% of patients were 65 years or older. An objective response occurred in 28 patients (32%); 8 patients had a complete response. Tumor PD-L1 expression did not affect response rates. The duration of response was ≥6 months in 92% of responders.3

The most common adverse effects of avelumab in clinical trials were fatigue (50%), musculoskeletal pain (32%), diarrhea (23%), nausea (22%), rash (22%), and infusion-site reactions (22%). Serious treatment-related adverse events occurred in 6% of patients. Grade 3 or 4 adverse events (lymphopenia, elevation of creatine kinase, transaminase increases) occurred in 5% of patients. As with PD-1 inhibitors, immune-mediated adverse effects including pneumonitis, colitis, nephritis, hepatitis, and endocrinopathies (hypothyroidism, adrenal insufficiency, type 1 diabetes) can occur.

The recommended dosage of Bavencio is 10 mg/kg infused IV over 60 minutes every 2 weeks. The cost of one 10-mL vial containing 200 mg of the drug is $1504; three months' treatment for a 60-kg patient would cost $27,072.4

1. PT Nghiem et al. PD-1 blockade with pembrolizumab in advanced Merkel-cell carcinoma. N Engl J Med 2016; 374:2542.
2. K Mantripragada and A Birnbaum. Response to anti-PD-1 therapy in metastatic Merkel cell carcinoma metastatic to the heart and pancreas. Cureus 2015; 7:e403.
3. HL Kaufman et al. Avelumab in patients with chemotherapy-refractory metastatic Merkel cell carcinoma: a multicentre, single-group, open-label, phase 2 trial. Lancet Oncol 2016; 17:1374.
4. Approximate WAC. WAC = wholesaler acquisition cost or manufacturer's published price to wholesalers; WAC represents a published catalogue or list price and may not represent an actual transactional price. Source: AnalySource® Monthly. June 5, 2017. Reprinted with permission by First Databank, Inc. All rights reserved. ©2017. www.fdbhealth.com/policies/drug-pricing-policy.

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The FDA has approved two new oral kinase inhibitors for treatment of unresectable or metastatic melanoma: dabrafenib (Tafinlar – GSK) for melanomas with BRAF V600E mutations and trametinib (Mekinist – GSK) for melanomas with either BRAF V600E or V600K mutations. Dabrafenib is not recommended for patients with wild-type BRAF (BRAF-negative) melanoma, and trametinib is not recommended for patients who have received prior BRAF-inhibitor therapy.

The FDA has approved vismodegib (vis moe deg´ ib; Erivedge – Genentech), the first hedgehog (Hh) pathway inhibitor, for oral treatment of metastatic basal cell cancer, locally advanced basal cell carcinoma that has recurred after surgery, or locally advanced basal cell carcinoma in adults who are not candidates for surgery or radiation.

The FDA has approved vemurafenib (Zelboraf – Genentech), a kinase inhibitor, for treatment of unresectable or metastatic melanoma with the BRAF V600E mutation, which is found in 30-60% of melanomas. An FDA-approved test can detect the mutation in DNA from melanoma tissue.

In the absence of randomized studies demonstrating an impact on mortality, the US Preventive Services Task Force (USPSTF) has found the evidence insufficient to recommend a routine whole-body examination for melanoma and other skin cancers.

The FDA has approved ipilimumab (Yervoy – Bristol-Myers Squibb), a recombinant human monoclonal antibody, for treatment of unresectable or metastatic melanoma.

Sunscreens are widely used now, but some questions remain about their effectiveness and safety.

Sunscreens are an important component of photoprotection. A new definition of their effectiveness has been proposed, and some issues have arisen concerning their safety.

Ecamsule (terephthalylidene dicamphor sulfonic acid), the first new sunscreen agent to be approved by the FDA in 18 years, is now available in the US in a moisturizer called Anthelios SX. Ecamsule has been used in Canada and Europe for more than 10 years.