Abstract Background The anti-programmed cell death-1 (PD-1) inhibitors pembrolizumab and nivolumab alone or in combination with ipilimumab have shown improved objective response rates and ...progression-free survival compared to ipilimumab only in advanced melanoma patients. Anti-PD-1 therapy demonstrated nearly equal clinical efficacy in patients who had progressed after ipilimumab or were treatment-naïve. However, only limited evidence exists regarding the efficacy of ipilimumab alone or in combination with nivolumab after treatment failure to anti-PD-therapy. Patients and methods A multicenter retrospective study in advanced melanoma patients who were treated with nivolumab (1 or 3 mg/kg) and ipilimumab (1 mg or 3 mg/kg) or ipilimumab (3 mg/kg) alone after treatment failure to anti-PD-1 therapy was performed. Patient, tumour, pre- and post-treatment characteristics were analysed. Results In total, 47 patients were treated with ipilimumab (ipi-group) and 37 patients with ipilimumab and nivolumab (combination-group) after treatment failure to anti-PD-1 therapy. Overall response rates for the ipi- and the combination-group were 16% and 21%, respectively. Disease control rate was 42% for the ipi-group and 33% for the combination-group. One-year overall survival rates for the ipi- and the combination-group were 54% and 55%, respectively. Conclusions Ipilimumab should be considered as a viable treatment option for patients with failure to prior anti-PD-1 therapy, including those with progressive disease as best response to prior anti-PD-1. In contrast, the combination of ipilimumab and nivolumab appears significantly less effective in this setting compared to treatment-naïve patients.
Sentinel lymph node (SLN) biopsy should be performed with the technical expertise required to correctly identify the sentinel node, in the context of understanding both the likelihood of positivity ...in a given patient and the prognostic significance of a positive or negative result. National Comprehensive Cancer Network guidelines recommend SLN biopsy for all cutaneous melanoma patients with primary tumor thickness greater than 1 mm and in select patients with thickness between 0.8 and 1 mm, yet admit a lack of consistent clarity in its utility for prognosis and therapeutic value in tumors < 1 mm and leave the decision for undergoing the procedure up to the patient and treating physician. Recent studies have evaluated specific patient populations, tumor histopathologic characteristics, and gene expression profiling and their use in predicting SLN positivity. These data have given insight into improving the physician’s ability to potentially predict SLN positivity, shedding light on if and when omission of SLN biopsy in specific patients based on clinicopathological characteristics might be appropriate. This review provides discussion and insight into these recent advancements.
Acral lentiginous melanoma is a rare subtype of melanoma generally associated with poor outcomes, even when diagnosed at an early stage. The tumor genetic profile remains poorly understood, but it is ...known to have a suppressed immune environment compared to that of non-acral cutaneous melanomas, which limits therapy options. There is significant attention on the development of novel therapeutic approaches, although studies are limited due to disease rarity. For local disease, wide local excision remains the standard of care. Due to frequent under-staging on preoperative biopsy, wider margins and routine sentinel lymph node biopsy may be considered if morbidity would not be increased. For advanced disease, anti-PD1 monotherapy or combination therapy with anti-PD1 and anti-CTLA4 agents have been used as first-line treatment modalities. Anti-PD1 and anti-CTLA4 combination therapies have been shown to be particularly beneficial for patients with BRAF-mutant acral lentiginous melanoma. Other systemic combination regimens and targeted therapy options may be considered, although large studies with consistent results are lacking. Regional and intralesional therapies have shown promise for cutaneous melanomas, but studies generally have not reported results for specific histologic subtypes, especially for acral melanoma. Overall, the unique histologic and genetic characteristics of acral lentiginous melanoma make therapy options significantly more challenging. Furthermore, studies are limited, and data reporting has been inconsistent. However, more prospective studies are emerging, and alternative therapy pathways specific to acral lentiginous melanoma are being investigated. As further evidence is discovered, reliable treatment guidelines may be developed.
Management of in-transit melanoma encompasses a variety of possible treatment pathways and modalities. Depending on the location of disease, number of lesions, burden of disease and patient ...preference and characteristics, some treatments may be more beneficial than others. After full body radiographic staging is performed to rule out metastatic disease, curative therapy may be performed through surgical excision, intraarterial regional perfusion and infusion therapies, intralesional injections, systemic therapies or various combinations of any of these. While wide excision is limited in indication to superficial lesions that are few in number, the other listed therapies may be effective in treating unresectable disease. Where intraarterial perfusion based therapies have been shown to successfully treat extremity disease, injectable therapies can be used in lesions of the head and neck. Although systemic therapies for in-transit melanoma have limited specific data to support their primary use for in-transit disease, there are patients who may not be eligible for any of the other options, and current clinical trials are exploring the use of concurrent and sequential use of regional and systemic therapies with early results suggesting a synergistic benefit for oncologic response and outcomes.
Major advances in the understanding of the pathophysiology of melanoma have led to a new era of melanoma treatment with targeted therapy and immunotherapies. Since 2011, four new classes of ...medications with unique mechanisms of action have been approved, which allow melanoma to be treated at many different stages in its development. These include the checkpoint inhibitors anti-PD1/PDL-1 and anti-CTLA4, as well as BRAF inhibitors and MEK inhibitors. The latter two were developed to directly inhibit key components in the MAP kinase pathway with significant breakthrough in the treatment of metastatic and unresectable melanoma. In this review, we discuss the development of targeted therapy of melanoma up to the latest agents encorafenib and binimetinib, including mechanisms of action, adverse effects, and the latest data on treatment response. Current ongoing trials will continue to elucidate these medications and their ultimate impact on melanoma therapy.
Reply to A. Mangla and E. Hindié Moncrieff, Marc D; Sondak, Vernon K; Thompson, John F ...
Journal of clinical oncology,
02/2023, Letnik:
41, Številka:
6
Journal Article