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. 2021 May;10(10):3155-3164.
doi: 10.1002/cam4.3760. Epub 2021 May 1.

Decreased survival in patients treated by chemotherapy after targeted therapy compared to immunotherapy in metastatic melanoma

Marie-Alix Mangin  1 , Amélie Boespflug  1   2 , Delphine Maucort Boulch  3 , Charles-Hervé Vacheron  3   4 , Isabelle Carpentier  5 , Luc Thomas  1   2 , Stéphane Dalle  1   2
Affiliations

Decreased survival in patients treated by chemotherapy after targeted therapy compared to immunotherapy in metastatic melanoma

Marie-Alix Mangin et al. Cancer Med. 2021 May.

Abstract

Background: Cytotoxic chemotherapy (CC) is currently used in metastatic melanoma after patients have developed resistance to immune checkpoint inhibitors (ICI) and/or Mitogen-Activated Protein Kinase inhibitors (MAPKi). We sought to evaluate if a previous treatment by ICI or MAPKi influences clinical outcomes in patients treated by CC in metastatic melanoma.

Methods: Eighty-eight patients with a metastatic melanoma, treated by CC after a previous treatment by ICI or MAPKi between January 2009 and October 2019, were retrospectively analyzed. Progression-Free-Survival (PFS), Overall Survival (OS), Overall Response Rate (ORR), and Disease Control Rate (DCR) were evaluated in patients treated by CC according to their prior treatment by ICI or MAPKi.

Results: Patients treated by CC after ICI tended to have a better median PFS (2.81 months (2.39-5.30) versus 2.40 months (0.91-2.75), p = 0.023), median OS (6.03 months (3.54-11.54) versus 4.44 months (1.54-8.59), p = 0.27), DCR (26.0% vs. 10.5%, p = 0.121) and ORR (22.0% vs. 7.9% p = 0.134) than those previously treated by MAPKi.

Conclusions: A prior treatment by an MAPKi may be associated with a worse response to CC than ICI, and further investigations should be performed to confirm if there is a clinical benefit to propose CC in this setting.

Keywords: cytotoxic chemotherapy; immunotherapy; melanoma; nivolumab; pembrolizumab; targeted therapy.

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Conflict of interest statement

SD is a principal investigator in clinical trials sponsored by BMS, MSD, Novartis, Amgen, and Roche. SD received institutional research grants from BMS, Roche and MSD. The other authors declare no conflict of interest in relation to this article.

Figures

FIGURE 1
FIGURE 1
Flowchart of the study cohort. CC, Cytotoxic Chemotherapy; ICI, Immune Checkpoint Inhibitors; MAPKi, MAPK inhibitors; UMM, unresecable or/and metastatic melanoma
FIGURE 2
FIGURE 2
Progression‐Free Survival (A) and Overall Survival (B) to chemotherapy in function prior treatment by immunotherapy or MAPKi. This figure shows the Kaplan‐Meier Progression‐Free Survival and Overall Survival curves of all patients included in the study in function of their prior treatment before CC. (A) logrank test: 0.023; (B)logrank test: 0.27
See this image and copyright information in PMC

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