Abstract
Background
Immune checkpoint inhibitors are now standard-of-care treatments for metastatic cutaneous melanoma. However, for rare sub-groups, such as mucosal melanomas, few published data are available, and with no established therapeutic guidelines. Our objective was to assess the response to anti-CTLA4 and anti-PD1 immunotherapy in patients with mucosal melanomas.
Methods
We performed a single-center, prospective cohort analysis of patients with non-surgical locally advanced and/or metastatic mucosal melanoma receiving anti-CTLA4 and/or anti-PD1 immunotherapy from 2010 to 2016.
Results
Forty-four patients were enrolled, including 18 (40.9%) with head and neck, 12 (27.3%) with vulvo-vaginal and 14 (31.8%) with ano-rectal primary tumours. Eleven (25%) patients had stage 3 disease, and 11 (25%) had distant metastases. The first-line immunotherapy was ipilimumab in 24 patients and pembrolizumab in 20. The objective response rate (ORR) was 8.2% (one complete response) for ipilimumab and 35% (four complete responses) for pembrolizumab. No significant difference was observed for primary tumour location. The median follow-up was 24 months (range 4–73). The median progression-free survival (PFS) in the first-line ipilimumab and pembrolizumab groups was 3 months [95% confidence interval (CI) 2.5–4.6] and 5 months (95% CI 2.6–33.1), respectively (p = 0.0147).
Conclusion
In the patients with unresectable and/or metastatic mucosal melanoma, we found ORR and PFS rates comparable to those in patients with cutaneous melanoma, with no significant differences in the types of mucosal surfaces involved. Anti-PD1 therapy has a more favorable benefit-risk ratio than ipilimumab and should be used preferentially.
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Abbreviations
- BRAF:
-
B-Raf proto-oncogene, serine/threonine kinase
- BRCA1:
-
Breast cancer 1
- cKIT:
-
KIT proto-oncogene, receptor tyrosine kinase
- CR:
-
Complete response
- DCR:
-
Disease control rate
- DOR:
-
Duration of response
- iRECIST:
-
Immune response evaluation criteria in solid tumours
- irRC:
-
Immune-related response criteria
- MBD4:
-
Methyl-CpG-binding domain 4
- NF1:
-
Neurofibromin 1
- NRAS:
-
NRAS proto-oncogene, GTPase
- ORR:
-
Objective response rate
- PD:
-
Progressive disease
- SD:
-
Stable disease
- SF3B1:
-
Splicing factor 3b subunit 1
- SNV:
-
Somatic nucleotide variants
- TG:
-
Tumour growth
- TGR:
-
Tumor growth rate
- V0:
-
Tumour volume at baseline
- Vt :
-
Tumour volume at time t
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AM-P, FJ, AMME, LD and CR conceptualized the manuscript, harmonized and edited the text and references and produced the figures. CR and IG performed statistical analysis. RGHG, SA, SR, J-YS and SV were responsible for data collection and analysis. All the authors contributed to the writing and editing of the manuscript. All the authors approved the final version.
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The translational research study NCT02105168 was approved by the Institutional Review Board at Gustave Roussy Cancer Campus on April 7, 2014. All the methods and procedures associated with this study were conducted in accordance with the ethical standards as laid down in the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards.
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All the patients have given their written authorization to perform research on their tumour samples by signing the Institutional Tumor Bank form (before April 2014) or the form of the translational research study NCT02105168. All the patients provided written informed consent to the use of their anonymized data in scientific studies.
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Moya-Plana A, Herrera Gómez RG, Rossoni C, Dercle L, Ammari S, Girault I et al. “Response assessment to anti-CTLA4 or/and anti-PD1 immunotherapy in mucosal melanomas”. American Society of Clinical Oncology (ASCO) Annual Meeting, June 2018 Chicago, USA. [Abstract #221719].
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Moya-Plana, A., Herrera Gómez, R.G., Rossoni, C. et al. Evaluation of the efficacy of immunotherapy for non-resectable mucosal melanoma. Cancer Immunol Immunother 68, 1171–1178 (2019). https://doi.org/10.1007/s00262-019-02351-7
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DOI: https://doi.org/10.1007/s00262-019-02351-7