Chemotherapy as an optimal treatment option after failure of immunotherapy and targeted therapy in advanced and metastatic melanoma.

Abstract

Background: Currently, there is no standard option that can be routinely recommended for the treatment of advanced melanoma after failure of modern immunotherapy and/or targeted therapy. Chemotherapy is an option, but its role is considered to be questionable. These doubts are based on historical experiences with chemotherapy, however, there is a lack of evidence of chemotherapy effectiveness after previous treatment with modern systemic therapy.

Patients and methods: At our institution, we managed to collect a set of 23 patients with advanced cutaneous melanoma who failed modern systemic treatment based on anti-PD-1 antibody immunotherapy or after failure of BRAFi (+MEKi) targeted treatments in the years 2017-2023. Dacarbazine monochemotherapy was indicated as further line systemic treatment for all these patients. The treatment effect was evaluated according to the RECIST/iRECIST criteria, and we also earned survival data for all patients.

Results: In our group, we observed substantial treatment response rate (complete remission 3times, partial remission 6times, response rate 39 %, stable disease twice), as well as long duration of those responses. Overall survival from the start of the therapy on second- or third-line dacarbazine in this group was 14.7 months and progression free survival was 9.3 months. In cases where a clinical benefit was achieved (complete remission, partial remission, or stable disease - 11times, 48%), the progression-free survival and overall survival values are 16.4 and 23.3 months respectively.

Conclusion: These excellent results show that the role of chemotherapy in this indication should not be doubted. Obviously, this raises questions about the reasons why these unexpectedly good results were achieved. We should seriously consider the possibility that previous immunotherapy does have a sensitizing and potentiating effect for subsequent chemotherapy.