Management of metastatic cutaneous melanoma: updates in clinical practice

Schvartsman, Gustavo; Taranto, Patrícia; Glitza, Isabella C.; Agarwala, Sanjiv S.; Atkins, Michael B.; Buzaid, Antônio C.

doi:10.1177/1758835919851663

Cited by 33 publications

(36 citation statements)

References 106 publications

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“…In the case of checkpoint inhibitors, the use of immunotherapy as a monotherapy is preferred in most patients due to its low toxicity. The combination of nivolumab and ipilimumab should be recommended especially in patients with asymptomatic CNS metastases [50][51][52]. However, the sequence of therapies, especially in patients with the present mutation in the BRAF gene, remains a problem.…”

Section: Strategy Of Management Of Patients With Advanced Melanomamentioning

confidence: 99%

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Combined or sequential treatment of advanced melanoma?

Cybulska-Stopa

Świtaj

Koseła-Paterczyk

2019

Nowotwory. Journal of Oncology

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Melanoma is a malignant neoplasm with a very high rate of growth in the number of cases. In Poland, in the years 1980-2010, the number of cases of melanoma increased threefold. Although the incidence rates of melanoma are rising, the mortality rate due to melanoma is falling. In recent years, the treatment of patients with melanoma has changed to a great extent. Thanks to the development of molecular research, the presence of specific mutations in melanoma cells was discovered. The progress in understanding the molecular mechanisms occurring in this neoplastic cells and the interaction between the immune system cells and melanoma cells contributed to the development of new classes of drugs: immunotherapy and targeted therapy. With the use of checkpoint inhibitors, long-term remission of the disease can be achieved, which has been confirmed in many clinical trials that have shown improvements in overall survival (OS) and progression free survival (PSF). However, the predominant problem is the low response rate to checkpoint inhibitors and the time between the initiation of therapy and the response to treatment. This is not the case with targeted therapies, where the response rate is high and the response time is very short. Therefore, a promising treatment strategy can be a combination of these two classes of drugs, so that one can try to achieve a quick and long-term response to the treatment. The paper discusses the current treatment options for melanoma patients in the spreading phase of the disease and analyzes the benefits of combined and sequential treatment.

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Section: Strategy Of Management Of Patients With Advanced Melanomamentioning

confidence: 99%

“…A very practical solution was proposed in the work by Schvartsman et al [50]. He distinguished two prognostic groups among patients with melanoma in inoperable grade III and in grade IV: low and high risk (table I).…”

Section: Combined Treatmentmentioning

confidence: 99%

Combined or sequential treatment of advanced melanoma?

Cybulska-Stopa

Świtaj

Koseła-Paterczyk

2019

Nowotwory. Journal of Oncology

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“…In recent years, the treatment of metastatic melanoma includes chemotherapy, checkpoint inhibitors and so on. However, due to poor efficacy, the use of chemotherapy has declined dramatically over time . Checkpoint inhibitors is an immunotherapy that has revolutionized the treatment of metastatic melanoma.…”

Section: Introductionmentioning

confidence: 99%

“…However, due to poor efficacy, the use of chemotherapy has declined dramatically over time. 7,8 Checkpoint inhibitors is an immunotherapy that has revolutionized the treatment of metastatic melanoma. With the application of checkpoint inhibitors, there are also some unique adverse reactions called immunotherapy-related adverse reactions (irae).…”

Section: Introductionmentioning

confidence: 99%

Hesperetin as an adjuvant augments protective anti‐tumour immunity responses in B16F10 melanoma by stimulating cytotoxic CD8⁺ T cells

et al. 2020

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Hesperetin (HES) is a dihydroflavone with the molecular formula of C16H14O6. It has been reported that Hesperetin has antioxidant and anticancer effects. Recent studies showed that it can also regulate immune responses. To assess its potential function as a vaccine adjuvant, we formulated HES with inactivated B16F10 melanoma cells and determined whether it would enhance the activation of antigen‐presenting cells by experiments in vivo and in vitro. We found that HES activated the PI3K‐Akt signalling pathway in antigen‐presenting cells (APCs), enhanced cytotoxic T lymphocyte (CTL) responses and deactivated tolerogenic T cells. We also observed that inactivated B16F10 cells in combination with HES vaccine inhibited the growth of mice tumours, resulting in improved overall survival compared to the effects of inactivated B16F10 cell vaccine. To verify that CD8+T cells play a key role in inhibiting the development of melanoma, we transferred the sorted CD8+T cells from immunized mice to B16F10 challenged models and found that the survival rate of tumour‐bearing mice was significantly prolonged. Taken together, these results suggest that hesperetin can be used as a potential adjuvant to improve tumour immune responses and antigen immunogenicity.

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“…many questions still remain to be answered: what is the best first-and second-line treatment or the best treatment sequence? New combinations of drugs, 'targeted therapies' combined with immunotherapies, immunotherapies combinations, and sequencing strategies are now underway in different clinical trials, highlighting the tendency towards a personalized medical approach [4][5][6][7][8][9].…”

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confidence: 99%

New insights in melanoma biology: Running fast towards precision medicine

Limonta

Queirolo

2019

Seminars in Cancer Biology

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Cutaneous melanoma is one of the most aggressive and the deadliest form of skin cancers characterized by a high degree of intra-tumor heterogeneity harboring mutations in genes involved in different signaling pathways. The majority of melanomas are diagnosed in the early stage and are treatable with surgical resection with a five-year survival rate ranging 82% to 98% for stages I-II. On the other hand, the prognosis of highly aggressive, late stage, melanoma is still very poor. For later stage and metastatic melanoma the alkylating agents, Dacarbazine or Temozolomide were the earliest treatment option; however, patients easily become resistant to these drugs and they also have serious side effects with low overall response and survival rates. 'Targeted therapies', such as Vemurafenib and Dabrafenib (BRAF V600E inhibitors) , were developed in order to specifically target mutated proteins, with a response rate around 50%; however, most patients relapse within few months [1]. The combination of BRAF inhibitors with MEK inhibitors, such as Cobimetinib and Trametinib, achieved response rates as high as 70%; however, most patients still face progressive disease even if treated with combination therapy, with less than 25% of patients being progression-free at 3 years. Along with the development of 'targeted therapies', the immune-checkpoint inhibitors, such as Ipilimumab (a CTLA-4 inhibitor), Nivolumab and Pembrolizumab (PD-1 inhibitors), were developed to improve the endogenous antitumor immune response. However, they are effective in only a subset of patients and may be associated with serious side effects and the development of acquired resistance in initially responders [2, 3]. Thus,

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Management of metastatic cutaneous melanoma: updates in clinical practice

Cited by 33 publications

References 106 publications

Combined or sequential treatment of advanced melanoma?

Combined or sequential treatment of advanced melanoma?

Hesperetin as an adjuvant augments protective anti‐tumour immunity responses in B16F10 melanoma by stimulating cytotoxic CD8⁺ T cells

New insights in melanoma biology: Running fast towards precision medicine

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Management of metastatic cutaneous melanoma: updates in clinical practice

Cited by 33 publications

References 106 publications

Combined or sequential treatment of advanced melanoma?

Combined or sequential treatment of advanced melanoma?

Hesperetin as an adjuvant augments protective anti‐tumour immunity responses in B16F10 melanoma by stimulating cytotoxic CD8+ T cells

New insights in melanoma biology: Running fast towards precision medicine

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Hesperetin as an adjuvant augments protective anti‐tumour immunity responses in B16F10 melanoma by stimulating cytotoxic CD8⁺ T cells