Efficacy and safety of ipilimumab 3mg/kg in patients with pretreated, metastatic, mucosal melanoma

Vecchio, Michele Del; Guardo, Lorenza Di; Ascierto, Paolo A.; Grimaldi, Antonio; Chiarion-Sileni, Vanna; Pigozzo, Jacopo; Ferraresi, Virginia; Nuzzo, Carmen; Rinaldi, Gaetana; Testori, Alessandro; Ferrucci, Pier Francesco; Marchetti, Paolo; Galitiis, Federica De; Queirolo, Paola; Tornari, Elena; Marconcini, Riccardo; Calabrò, Luana; Maio, Michele

doi:10.1016/j.ejca.2013.09.007

Cited by 134 publications

(100 citation statements)

References 32 publications

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“…One (1/10) patient suffered from a severe adverse drug reaction (colitis with sigma perforation, uveitis and otitis interna), and therapy had to be stopped early (10%). These results correlate with the previously reported response rates for immunotherapy in mucosal melanomas of 3-12% PR and 16-43% SD as well as the published severe adverse drug reaction incidence [34,35]. Also, other authors described CR in single cases in mucosal and uveal melanoma [35,36].…”

Section: Discussionsupporting

confidence: 81%

Noncutaneous Melanomas: A Single-Center Analysis

Prete¹,

Chaloupka²,

Holzmann³

et al. 2015

Dermatology

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Background: The optimal treatment algorithm for noncutaneous melanomas must yet be established. Objective: To compare systemic treatment-relevant mutational status, metastatic pattern and response to systemic treatment in noncutaneous melanoma. Methods: Retrospective single-center study analyzing 64 noncutaneous melanoma patients treated between January 2006 and September 2013. Results: c-KIT mutations were found exclusively in vulvovaginal melanoma (4/7). Overall status for NRAS and BRAF mutations was low (1/7 and 0/21 detected mutations, respectively). Seven out of 7 vulvovaginal and 6/13 sinonasal melanomas first metastasized to lymph nodes, whereas 18/22 ocular melanomas first metastasized to the liver. Response to systemic treatment in vulvovaginal melanomas was best for imatinib with a disease control rate of 3/3 and overall for ipilimumab with a disease control rate of 3/10. Sorafenib was associated with adverse drug reactions (6/13) and poor results. Conclusion: Noncutaneous melanomas show few tumor-signaling pathway mutations and distinct metastasization patterns. Immunotherapy induces response rates in mucosal melanoma similar to those in cutaneous melanoma.

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Section: Discussionsupporting

confidence: 81%

Noncutaneous Melanomas: A Single-Center Analysis

Prete¹,

Chaloupka²,

Holzmann³

et al. 2015

Dermatology

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“…Recently, ipilimumab has been evaluated in advanced mucosal melanoma in an Italian cohort, showing that ipilimumab is active in some patients with mucosal melanoma, with a disease control rate about 23.1% (35). However, it is still largely unknown about the effectiveness of these therapies as adjuvant therapy in patients with mucosal melanoma.…”

Section: Survivalmentioning

confidence: 99%

Phase II Randomized Trial Comparing High-Dose IFN-α2b with Temozolomide Plus Cisplatin as Systemic Adjuvant Therapy for Resected Mucosal Melanoma

Lian

Cui

et al. 2013

Clinical Cancer Research

159

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Purpose: Mucosal melanoma is rare and associated with extremely poor prognosis. However, standard adjuvant therapy for mucosal melanoma has not been established. We conducted a randomized phase II clinical trial in patients with resected mucosal melanoma to compare the efficacy and safety of high-dose IFN-a2b (HDI) and temozolomide-based chemotherapy as adjuvant therapy.Experimental Design: Patients with mucosal melanoma in stage II/III after surgery were randomized into three groups: observation group (group A, surgery alone), HDI group (group B, treated with 15 Â 10 6 U/m 2 /d IFN-a2b, followed by 9 Â 10 6 U IFN-a2b), and temozolomide (200 mg/m 2 /d) plus cisplatin (75 mg/m 2 ) group (group C). The endpoints were relapse-free survival (RFS), overall survival (OS), and toxicities.Results: One hundred and eighty-nine patients were enrolled and finally analyzed. With a median follow-up of 26.8 months, the median RFS was 5.4, 9.4, and 20.8 months for group A, B, and C, respectively. Estimated median OS for group A, B, and C was 21.2, 40.4, and 48.7 months, respectively. Patients treated with temozolomide plus cisplatin showed significant improvements in RFS (P < 0.001) and OS (P < 0.01) than those treated with either HDI or surgery alone. Toxicities were generally mild to moderate.Conclusion: Both temozolomide-based chemotherapy and HDI are effective and safe as adjuvant therapies for resected mucosal melanoma as compared with observation alone. However, HDI tends to be less effective than temozolomide-based chemotherapy for patients with resected mucosal melanoma in respect to RFS. The temozolomide plus cisplatin regimen might be a better choice for patients with resected mucosal melanoma.

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“…In uveal melanoma, 2 of 39 patients (5.1%) had an objective response to ipilimumab; the median OS was 9.6 months [5]. Reports from the Italian Expanded Access Program of ipilimumab for patients receiving prior therapies also reported low response rates (12% and 5%) and median OS (6.4 and 6 months) for mucosal and uveal melanoma, respectively [7,8].…”

Section: Discussionmentioning

confidence: 99%

“…Despite low response rates by classically determined methods, approximately 20% of patients survive 3-5 years after starting therapy, nearly twice that of historical controls [1,3,4]. Recently, retrospective reviews have shown that ipilimumab has modest clinical activity in uveal and mucosal melanomas, uncommon subtypes of this disease [5][6][7][8]. Although these subgroups have not been directly compared with cutaneous melanoma, the objective response rate and median overall survival appears inferior to unselected, largely cutaneous, melanoma populations.…”

Section: Introductionmentioning

confidence: 99%

Clinical Activity of Ipilimumab in Acral Melanoma: A Retrospective Review

Johnson¹,

Peng

Abramson³

et al. 2015

The Oncologist

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Background. Ipilimumab improves overall survival (OS) in advanced melanoma. Acral melanoma is an uncommon clinical subtype of this disease associated with poor prognosis. The clinical activity of ipilimumab has not been well‐defined in advanced acral melanoma. Methods. We retrospectively reviewed the demographics, treatment history, and clinical outcomes for all patients with acral melanoma treated with ipilimumab from two academic centers between February 2006 and June 2013. Using Cox proportional hazards models, we assessed for factors that correlated with OS. Results. A total of 35 patients with acral melanoma received ipilimumab. Melanomas arose on volar surfaces (n = 28) and subungual sites (n = 7); stage M1c disease was present in 54%, and 45% had elevated serum lactate dehydrogenase (LDH). Best response by RECIST 1.1 criteria was complete response in 1 patient, partial response in 3, and stable disease (SD) in 4 for an objective response rate (ORR) of 11.4% and a clinical benefit rate (ORR + SD) at 24 weeks of 22.9%. Median progression‐free survival was 2.5 months (95% confidence interval [CI]: 2.3–2.7 months); median OS was 16.7 months (95% CI: 10.9–22.5 months). Normal LDH and absolute lymphocyte count ≥1,000 at 7 weeks predicted longer OS. Immune‐related adverse events (irAEs) were noted in 16 patients including 7 with grade 3/4 irAEs (20%). Conclusion. Ipilimumab is clinically active in acral melanoma with similar ORR and OS compared with unselected melanoma populations. Ipilimumab remains a viable therapeutic option for patients with advanced acral melanoma. Implications for Practice: Ipilimumab is a commonly used immune therapy that improves survival in metastatic melanoma. The clinical activity of ipilimumab in certain rare melanoma subtypes, such as uveal or mucosal melanomas, is suboptimal. Acral melanoma is another unusual subtype of this disease that arises on the palms, soles, and nailbeds. In this study of 35 patients with acral melanoma from 2 centers, ipilimumab was found to have activity that appears equivalent to unselected melanoma (response rate of 11.4%, median overall survival of 16.7 months). Ipilimumab remains a viable treatment option for this melanoma subpopulation.

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Efficacy and safety of ipilimumab 3mg/kg in patients with pretreated, metastatic, mucosal melanoma

Cited by 134 publications

References 32 publications

Noncutaneous Melanomas: A Single-Center Analysis

Noncutaneous Melanomas: A Single-Center Analysis

Phase II Randomized Trial Comparing High-Dose IFN-α2b with Temozolomide Plus Cisplatin as Systemic Adjuvant Therapy for Resected Mucosal Melanoma

Clinical Activity of Ipilimumab in Acral Melanoma: A Retrospective Review

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