Anti-PD-1 alone or in combination with anti-CTLA-4 for advanced melanoma patients with liver metastases

Ines Pires da Silva; Isabel Li; Selma Ugurel; Patricio Serra-Bellver; Avanti Andhale; Hannah Burnette; Francisco Aya; Jordan W Conway; Jorja Braden; Matteo S Carlino; Alexander M Menzies; Michael Weichenthal; Peter Mohr; Ralf Gutzmer; Ana M Arance; Douglas B Johnson; Paul Lorigan; Dirk Schadendorf; Serigne N Lo; Georgina V Long

doi:10.1016/j.ejca.2024.114101

Anti-PD-1 alone or in combination with anti-CTLA-4 for advanced melanoma patients with liver metastases

Eur J Cancer. 2024 Jul:205:114101. doi: 10.1016/j.ejca.2024.114101. Epub 2024 May 7.

Authors

Ines Pires da Silva¹, Isabel Li², Selma Ugurel³, Patricio Serra-Bellver⁴, Avanti Andhale⁴, Hannah Burnette⁵, Francisco Aya⁶, Jordan W Conway⁷, Jorja Braden⁷, Matteo S Carlino⁸, Alexander M Menzies⁹, Michael Weichenthal¹⁰, Peter Mohr¹¹, Ralf Gutzmer¹², Ana M Arance⁶, Douglas B Johnson⁵, Paul Lorigan⁴, Dirk Schadendorf¹³, Serigne N Lo¹⁴, Georgina V Long¹⁵

Affiliations

¹ Melanoma Institute Australia, University of Sydney, Sydney, NSW, Australia; Faculty of Medicine & Health, The University of Sydney, NSW, Australia; Charles Perkins Centre, The University of Sydney, NSW, Australia; Crown Princess Mary Cancer Centre Westmead, Blacktown Hospital, Sydney, Australia. Electronic address: [email protected].
² Melanoma Institute Australia, University of Sydney, Sydney, NSW, Australia.
³ Department of Dermatology, University Hospital Essen, and German Cancer Consortium (DKTK) partner site Essen/Düsseldorf, Essen, Germany.
⁴ The Christie NHS Foundation Trust, Manchester, UK.
⁵ Vanderbilt University Medical Center, Nashville, TN, United States.
⁶ Department of Medical Oncology, IDIBAPS, Hospital Clínic, Barcelona, Spain.
⁷ Melanoma Institute Australia, University of Sydney, Sydney, NSW, Australia; Faculty of Medicine & Health, The University of Sydney, NSW, Australia; Charles Perkins Centre, The University of Sydney, NSW, Australia.
⁸ Melanoma Institute Australia, University of Sydney, Sydney, NSW, Australia; Crown Princess Mary Cancer Centre Westmead, Blacktown Hospital, Sydney, Australia.
⁹ Melanoma Institute Australia, University of Sydney, Sydney, NSW, Australia; Faculty of Medicine & Health, The University of Sydney, NSW, Australia; Royal North Shore and Mater Hospitals, Sydney, Australia.
¹⁰ University Skin Cancer Center Kiel, University Hospital of Schleswig-Holstein, Kiel, Germany.
¹¹ Elbe-Klinikum Buxtehude, Buxtehude, Germany.
¹² Ruhr University Bochum Campus Minden, Minden, Germany.
¹³ Department of Dermatology, University Hospital Essen, and German Cancer Consortium (DKTK) partner site Essen/Düsseldorf, Essen, Germany; Westdeutsches Tumorzentrum (WTZ) & National Center for Tumor Diseases (NCT-West), Campus Essen & University Alliance Ruhr, Research Center One Health, University Duisburg-Essen, Essen, Germany.
¹⁴ Melanoma Institute Australia, University of Sydney, Sydney, NSW, Australia; Faculty of Medicine & Health, The University of Sydney, NSW, Australia.
¹⁵ Melanoma Institute Australia, University of Sydney, Sydney, NSW, Australia; Faculty of Medicine & Health, The University of Sydney, NSW, Australia; Charles Perkins Centre, The University of Sydney, NSW, Australia; Royal North Shore and Mater Hospitals, Sydney, Australia. Electronic address: [email protected].

PMID: 38735161
DOI: 10.1016/j.ejca.2024.114101

Abstract

Background: The combination of anti-PD-1 and anti-CTLA-4 has been associated with improvement in response and survival over anti-PD-1 monotherapy in unselected patients with advanced melanoma. Whether patients with liver metastases also benefit from the combination of anti-PD-1 and anti-CTLA-4 over anti-PD-1, is unclear. In this study, we sought to assess whether the combination of anti-PD-1 and anti-CTLA-4 leads to better response, progression-free survival and overall survival, compared with anti-PD-1 monotherapy for patients with liver metastases.

Methods: We have conducted an international multicentre retrospective study. Patients with advanced melanoma with liver metastases treated with 1st line anti-PD1 monotherapy or with anti-CTLA-4 were included. The endpoints of this study were: objective response rate, progression-free survival and overall survival.

Results: With a median follow-up from commencement of anti-PD-1 monotherapy or in combination with anti-CTLA-4 of 47 months (95% CI, 42-51), objective response rate was higher with combination therapy (47%) versus anti-PD-1 monotherapy (35%) (p = 0.0027), while progression-free survival and overall survival were not statistically different between both treatment groups. However, on multivariable analysis with multiple imputation for missing values and adjusting for predefined variables, combination of anti-PD1 and anti-CTLA-4 was associated with higher objective response (OR 2.21, 1.46 - 3.36; p < 0.001), progression-free survival (HR 0.73, 0.57 - 0.92; p = 0.009) and overall survival (HR 0.71, 0.54 - 0.94; p = 0.018) compared to anti-PD1 monotherapy.

Conclusions: Findings from this study will help guide treatment selection for patients who present with liver metastases, suggesting that combination therapy should be considered for this group of patients.

Keywords: Advanced melanoma; Anti-CTLA-4″; Anti-PD-(L)1; Combination immunotherapy; Immunotherapy; Liver metastases”; Metastatic melanoma.

Publication types

Multicenter Study

MeSH terms

Adult
Aged
Aged, 80 and over
Antineoplastic Combined Chemotherapy Protocols* / therapeutic use
CTLA-4 Antigen* / antagonists & inhibitors
Female
Humans
Immune Checkpoint Inhibitors* / therapeutic use
Liver Neoplasms* / drug therapy
Liver Neoplasms* / mortality
Liver Neoplasms* / secondary
Male
Melanoma* / drug therapy
Melanoma* / mortality
Melanoma* / secondary
Middle Aged
Programmed Cell Death 1 Receptor* / antagonists & inhibitors
Progression-Free Survival
Retrospective Studies
Skin Neoplasms / drug therapy
Skin Neoplasms / mortality
Skin Neoplasms / pathology

Substances

CTLA-4 Antigen
Programmed Cell Death 1 Receptor
Immune Checkpoint Inhibitors
CTLA4 protein, human
PDCD1 protein, human