Impact of prior treatment with immune checkpoint inhibitors on dacarbazine efficacy in metastatic melanoma

Br J Cancer. 2021 Sep;125(7):948-954. doi: 10.1038/s41416-021-01486-8. Epub 2021 Jul 14.

Abstract

Background: Despite its low efficacy, chemotherapy with dacarbazine remains an option in metastatic melanoma patients after failure of immune checkpoint inhibitors (ICI) ± targeted therapy. Some observations suggested an increased efficacy of chemotherapy in melanoma or lung cancer patients previously treated with ICI; we aimed to evaluate the efficacy of dacarbazine in a controlled-group study of patients pre-treated or not with ICI.

Methods: We retrospectively collected data from all consecutive patients treated with dacarbazine for advanced cutaneous melanoma without brain metastasis, in our skin cancer centre between June 2006 and September 2019. The primary endpoint was progression-free survival (PFS); secondary endpoints were overall response rates (ORR), overall survival (OS) and safety of dacarbazine.

Results: Among 72 patients, 17 (23.6%) received dacarbazine after ICI and 55 (76.3%) without prior ICI. Despite less favourable prognostic factors in patients ICI-pre-treated, median PFS was 4.27 months (range 0.89-43.69) in this group versus 2.04 months (range 1.25-39.25) P = 0.03 in non-ICI-pre-treated patients; ORR were 35.3% and 12.7%, respectively. The median OS and the occurrence of adverse events were similar in both groups.

Conclusion: Dacarbazine seems to offer a short-lived benefit in patients with progressive advanced disease despite ICI (±targeted therapy), and could be an alternative before considering best supportive care.

Publication types

  • Comparative Study

MeSH terms

  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents, Alkylating / therapeutic use*
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Case-Control Studies
  • Dacarbazine / therapeutic use*
  • Disease-Free Survival
  • Female
  • Humans
  • Immune Checkpoint Inhibitors / therapeutic use*
  • Male
  • Melanoma / drug therapy*
  • Melanoma / immunology
  • Middle Aged
  • Retrospective Studies
  • Treatment Outcome

Substances

  • Antineoplastic Agents, Alkylating
  • Immune Checkpoint Inhibitors
  • Dacarbazine