RESUMO
Immunotherapies have revolutionized the management of advanced cutaneous malignancies. However, some patients fail to respond to these therapies, others are ineligible because of comorbidities, and a minority of patients experience treatment-limiting systemic immune-related adverse events. To address these issues and expand treatment options for patients with early-stage disease, a variety of immunotherapies are being developed for direct intratumoral administration. Agents including oncolytic viruses, monoclonal antibodies, cytokines, peptides, and pattern-recognition receptor agonists have been engineered to evoke a local immune response while minimizing systemic toxicity and have shown favorable results in preclinical and early clinical testing. This review covers the current landscape of intratumoral immunotherapies for the treatment of cutaneous melanoma, squamous cell carcinoma, and basal cell carcinoma, highlighting the diverse array of agents being explored and their potential benefits and challenges.
RESUMO
Basal cell carcinoma (BCC) is one of the most common human cancers. Most cases of BCC are amenable to surgical and topical treatments with excellent prognosis if diagnosed timely and managed appropriately. However, in a small percentage of cases, it could be locally advanced BBC (laBCC) and not amenable to surgery or radiation, including recurrent, large tumors or tumors that invade deeper tissue. Hedgehog inhibitors (vismodegib and sonidegib) are approved as the first-line treatment of laBCC. PD-1 inhibitor immunotherapy (cemiplimab) is indicated for cases that progressed on or could not tolerate hedgehog inhibitors or when hedgehog inhibitors are contraindicated. Given the modest response and bothersome side effects of some of the agents above, there are reports of novel treatments, and clinical trials are currently evaluating multiple agents.
Assuntos
Antineoplásicos , Carcinoma Basocelular , Neoplasias Cutâneas , Humanos , Neoplasias Cutâneas/tratamento farmacológico , Proteínas Hedgehog , Recidiva Local de Neoplasia/tratamento farmacológico , Carcinoma Basocelular/tratamento farmacológico , Carcinoma Basocelular/induzido quimicamente , Prognóstico , Antineoplásicos/efeitos adversos , Anilidas/uso terapêutico , Anilidas/farmacologiaRESUMO
BACKGROUND: Cemiplimab (Libtayo®), a human monoclonal immunoglobulin G4 antibody to the programmed cell death-1 receptor, is approved for the treatment of patients with advanced cutaneous squamous cell carcinoma (CSCC), who are not candidates for curative surgery or curative radiation, using an every-3-weeks (Q3W) dosing interval. Pharmacokinetic modeling indicated that Ctrough of extended intravenous dosing of 600 mg every 4 weeks (Q4W) would be comparable to the approved intravenous dosage of 350 mg Q3W. We examined the efficacy, pharmacokinetics, and safety of cemiplimab dosed Q4W. METHODS: In this open-label, phase II trial (ClinicalTrials.gov identifier NCT02760498), the cohort of patients ≥18 years old with advanced CSCC received cemiplimab 600 mg intravenously Q4W for up to 48 weeks. Tumor measurements were recorded every 8 weeks. The primary endpoint was objective response rate by independent central review. RESULTS: Sixty-three patients with advanced CSCC were treated with cemiplimab. The median duration of follow-up was 22.4 months (range: 1.0-39.8). An objective response was observed in 39 patients (62%; 95% CI: 48.8% to 73.9%), with 22% of patients (n=14) achieving complete response and 40% (n=25) achieving partial response. The most common treatment-emergent adverse events were diarrhea, pruritus, and fatigue. CONCLUSIONS: Extended dosing of cemiplimab 600 mg intravenously Q4W exhibited substantial antitumor activity, rapid and durable responses, and an acceptable safety profile in patients with advanced CSCC. These results confirm that cemiplimab is a highly active therapy for advanced CSCC. Additional data would help ascertain the benefit-risk profile for the 600 mg intravenous dosing regimen compared with the approved regimen.