Are checkpoint inhibitors a valuable option for metastatic or unresectable vulvar and vaginal melanomas?

Quéreux, G.; Wylomanski, S.; Bouquin, R.; Saint‐Jean, M.; Peuvrel, L.; Knol, Anne-Chantal; Hanf, Matthieu; Dréno, Brigitte

doi:10.1111/jdv.14486

Cited by 16 publications

(14 citation statements)

References 6 publications

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“…In addition, three single-center retrospective studies showed an ORR from 0% to 16.7% in MM patients who received ipilimumab monotherapy. [27][28][29] Anti-PD-1 monoclonal antibodies Regarding anti-PD-1 immunotherapy, 22 studies with a total of 850 patients were identified ( ORR of 23.5%. Another phase II study of nivolumab (3 mg/kg) was performed on 24 Japanese patients with untreated stage III/IV or recurrent melanoma.…”

Section: Anti-ctla-4 Monoclonal Antibodiesmentioning

confidence: 99%

“…In addition, seven independent single-center, retrospective studies showed that MM patients treated with nivolumab had an ORR from 9.5% to 50.0% and a median PFS from 2.1 to 10.2 months. 29,[34][35][36][37][38][39] Pembrolizumab was independently assessed in four studies. 26,[40][41][42] An exploratory post hoc analysis of three randomized trials (KEYNOTE-001, KEYNOTE-002, and KEYNOTE-006) enrolled almost 1600 patients with stage III or IV melanoma.…”

Section: Anti-ctla-4 Monoclonal Antibodiesmentioning

confidence: 99%

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Immune checkpoint inhibitors in advanced or metastatic mucosal melanoma: a systematic review

Kan

Zhao

et al. 2020

Ther Adv Med Oncol

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Background: Conventional cytotoxic chemotherapy offers minor benefit to patients with mucosal melanoma (MM). Although immune checkpoint inhibitors (ICIs) have become the preferred approach in patients with advanced or metastatic cutaneous melanoma, the evidence of their clinical use for MM is still limited. This systematic review aims to summarize the efficacy and safety of ICIs in advanced or metastatic MM. Methods: We searched electronic databases, conference abstracts, clinical trial registers and reference lists for relevant studies. The primary outcomes included the overall response rate (ORR), median progression-free survival (PFS), median overall survival (OS), one-year PFS rate, and one-year OS rate. Results: This review identified 13 studies assessing anti-CTLA-4 monotherapy, 22 studies assessing anti-PD-1 monotherapy, two studies assessing anti-CTLA-4 and anti-PD-1 combination therapy, one study assessing anti-PD-1 antibodies combined with axitinib, and three studies assessing anti-PD-1 antibodies combined with radiotherapy. For most patients who received ipilimumab monotherapy, the ORR ranged from 0% to 17%, the median PFS was less than 5 months, and the median OS was less than 10 months. For patients who received nivolumab or pembrolizumab monotherapy, most studies showed an ORR of more than 15% and a median OS of more than 11 months. The combined administration of anti-CTLA-4 and anti-PD-1 agents showed benefits over single-agent therapy with an ORR of more than 33.3%. In a phase Ib trial of toripalimab in combination with axitinib, approximately half of patients had complete or partial responses. Three retrospective studies that investigated anti-PD-1 antibodies combined with radiotherapy showed an ORR of more than 50%, which was higher than each single modality treatment. Conclusions: Immune checkpoint inhibitors, especially anti-PD-1 monoclonal antibodies alone and in combination with anti-CTLA-4 monoclonal antibodies or other modalities, are promising treatment options for advanced or metastatic MM. However, high-level evidence is still needed to support the clinical application.

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Section: Anti-ctla-4 Monoclonal Antibodiesmentioning

confidence: 99%

Section: Anti-ctla-4 Monoclonal Antibodiesmentioning

confidence: 99%

Immune checkpoint inhibitors in advanced or metastatic mucosal melanoma: a systematic review

Kan

Zhao

et al. 2020

Ther Adv Med Oncol

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“…In a skin cancer department in France between 2013 and 2018, a study including 15 patients with unresectable or metastatic vulvovaginal melanoma was conducted [ 30 ]. Six patients were treated with ipilimumab.…”

Section: Resultsmentioning

confidence: 99%

Current Status and Prospects of Immunotherapy for Gynecologic Melanoma

Anko

Kobayashi

Banno

et al. 2021

JPM

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Gynecologic melanomas are rare and have a poor prognosis. Although immunotherapy (immune checkpoint inhibitors) and targeted therapy has greatly improved the systemic treatment of cutaneous melanoma (CM) in recent years, its efficacy in gynecologic melanomas remains uncertain because of the rarity of this malignancy and its scarce literature. This review aimed to evaluate the literature of gynecologic melanomas treated with immunotherapy and targeted therapy through a PubMed search. We identified one study focusing on the overall survival of gynecologic melanomas separately and five case series and nine case reports concentrating on gynecologic melanomas treated with an immune checkpoint inhibitor and/or targeted therapy. Furthermore, the KIT mutation has the highest rate among all mutations in mucosal melanoma types. The KIT inhibitors (Tyrosine kinase inhibitors: TKIs) imatinib and nilotinib could be the treatment options. Moreover, immune checkpoint inhibitors combined with KIT inhibitors may potentially treat cases of resistance to immune checkpoint inhibitors. However, because of the different conditions and a small number of cases, it is difficult to evaluate the efficacy of immunotherapy and targeted therapy for gynecologic melanoma rigorously at this time. Further prospective cohort or randomized trials of gynecologic melanoma alone are needed to assess the treatment with solid evidence.

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“…In a small cohort of six patients with metastatic vulvar/vaginal melanomas treated with an anti-CTLA-4 ICI, disease progression was observed in four patients, a stable disease in one patient (maintained for 11 months) and an important clinical response was obtained in one patient, achieving long survival (31 months). The 1-year survival rate was 33% [109] (Table 1). As previously mentioned, the RT plus ICIs combination can lead to important results when dealing with advanced neoplasms.…”

Section: Potential Role Of Icis In Rare Vulvar Tumor Types 41 Vulvar Melanomamentioning

confidence: 99%

Is There a Place for Immune Checkpoint Inhibitors in Vulvar Neoplasms? A State of the Art Review

Borella

Preti

Bertero

et al. 2020

IJMS

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Vulvar cancer (VC) is a rare neoplasm, usually arising in postmenopausal women, although human papilloma virus (HPV)-associated VC usually develop in younger women. Incidences of VCs are rising in many countries. Surgery is the cornerstone of early-stage VC management, whereas therapies for advanced VC are multimodal and not standardized, combining chemotherapy and radiotherapy to avoid exenterative surgery. Randomized controlled trials (RCTs) are scarce due to the rarity of the disease and prognosis has not improved. Hence, new therapies are needed to improve the outcomes of these patients. In recent years, improved knowledge regarding the crosstalk between neoplastic and tumor cells has allowed researchers to develop a novel therapeutic approach exploiting these molecular interactions. Both the innate and adaptive immune systems play a key role in anti-tumor immunesurveillance. Immune checkpoint inhibitors (ICIs) have demonstrated efficacy in multiple tumor types, improving survival rates and disease outcomes. In some gynecologic cancers (e.g., cervical cancer), many studies are showing promising results and a growing interest is emerging about the potential use of ICIs in VC. The aim of this manuscript is to summarize the latest developments in the field of VC immunoncology, to present the role of state-of-the-art ICIs in VC management and to discuss new potential immunotherapeutic approaches.

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Are checkpoint inhibitors a valuable option for metastatic or unresectable vulvar and vaginal melanomas?

Abstract: might not be limited to a maximum treatment area (e.g. 5% imiquimod is limited to 25 cm 2 ) and could be an attractive option

Cited by 16 publications

References 6 publications

Immune checkpoint inhibitors in advanced or metastatic mucosal melanoma: a systematic review

Immune checkpoint inhibitors in advanced or metastatic mucosal melanoma: a systematic review

Current Status and Prospects of Immunotherapy for Gynecologic Melanoma

Is There a Place for Immune Checkpoint Inhibitors in Vulvar Neoplasms? A State of the Art Review

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