Evolving impact of long-term survival results on metastatic melanoma treatment

Abstract

Melanoma treatment has been revolutionized over the past decade. Long-term results with immuno-oncology (I-O) agents and targeted therapies are providing evidence of durable survival for a substantial number of patients. These results have prompted consideration of how best to define long-term benefit and cure. Now more than ever, oncologists should be aware of the long-term outcomes demonstrated with these newer agents and their relevance to treatment decision-making. As the first tumor type for which I-O agents were approved, melanoma has served as a model for other diseases. Accordingly, discussions regarding the value and impact of long-term survival data in patients with melanoma may be relevant in the future to other tumor types. Current findings indicate that, depending on the treatment, over 50% of patients with melanoma may gain durable survival benefit. The best survival outcomes are generally observed in patients with favorable prognostic factors, particularly normal baseline lactate dehydrogenase and/or a low volume of disease. Survival curves from melanoma clinical studies show a plateau at 3 to 4 years, suggesting that patients who are alive at the 3-year landmark (especially in cases in which treatment had been stopped) will likely experience prolonged cancer remission. Quality-of-life and mixture-cure modeling data, as well as metrics such as treatment-free survival, are helping to define the value of this long-term survival. In this review, we describe the current treatment landscape for melanoma and discuss the long-term survival data with immunotherapies and targeted therapies, discussing how to best evaluate the value of long-term survival. We propose that some patients might be considered functionally cured if they have responded to treatment and remained treatment-free for at least 2 years without disease progression. Finally, we consider that, while there have been major advances in the treatment of melanoma in the past decade, there remains a need to improve outcomes for the patients with melanoma who do not experience durable survival.

Combination Therapy of Novel Oncolytic Adenovirus with Anti-PD1 Resulted in Enhanced Anti-Cancer Effect in Syngeneic Immunocompetent Melanoma Mouse Model

“…Furthermore, about 25% of the responders, despite ongoing therapy, develop relapses due to treatment resistance [ 25 , 62 ]. Nevertheless, metastatic melanoma responds better to immunotherapy compared to conventional chemotherapeutic drugs and radiotherapy [ 63 , 64 , 65 ]. Hence, combined treatment with novel oncolytic adenovirus and ICIs induces complementary antitumor response that could actually lead to more favorable therapeutic outcomes [ 66 , 67 , 68 , 69 ].…”

Anticancer Activity of Two Novel Hydroxylated Biphenyl Compounds toward Malignant Melanoma Cells

“…The therapeutic approach contrasting advanced melanoma, the most aggressive cutaneous tumor, has recently taken an encouraging trend, due to the development of new targeted and immunotherapies [ 13 ]. However, it remains the topic of a cure for patients either lacking a BRAF mutation or who are refractory to therapies, in addition to those that develop resistance to them [ 14 , 16 ]. The theme of finding new antitumor compounds able to front these issues is not new but still current, and natural compounds and their derivatives have often been investigated in such a direction.…”

“…The use of immunotherapeutic agents (i.e., the immune checkpoint inhibitors), given in sequence or combination with targeted therapies, is now achieving satisfactory clinical outcomes in large fractions of patients presenting alterations in candidate target genes. Actually, about 50% of metastatic melanoma patients gain long-term benefits from immune and target therapies, while chemotherapy is indicated only for patients who do not respond to them [ 13 , 14 ]. Overall, one could state that BRAF -mutated melanoma patients may indeed benefit of an additional treatment opportunity represented by the targeted therapies.…”

“…In other words, the therapeutic weaponry is more limited for patients with cutaneous melanoma lacking a BRAF mutation (about 50% of all cases) and for those with rare melanoma subtypes (e.g., uveal, acral, and mucosal). Moreover, about one-tenth of melanoma patients is innately resistant to therapy (primary resistance), whereas all the remaining ones become resistant following an initial response due to the activation of alternative proliferative pathways in the cancer cell (acquired resistance) [ 14 , 15 ]. Therefore, there remains a need to improve the outcomes for patients left the “orphans” of any therapy or for those who experience drug resistance, as well as to combine additional therapeutic compounds aimed at increasing the responsiveness to current treatments and, thus, at ameliorating the global prognosis [ 16 ].…”

Claisened Hexafluoro Inhibits Metastatic Spreading of Amoeboid Melanoma Cells

“…However, once melanoma cells spread to distant organs, mostly to the brain, lungs, liver, and small bowel, patients’ life expectancy strongly decreases. Even if in recent years new therapeutic approaches are increasing the overall survival of melanoma patients [ 17 ], new therapies aimed at targeting invasive cells and preventing their metastatic dissemination are urgently needed.…”