Systemic treatments for metastatic cutaneous melanoma

Crosby, Tom; Fish, R.G.; Coles, Bernadette; Mason, Malcolm David

doi:10.1002/14651858.cd001215

Cited by 86 publications

(62 citation statements)

References 15 publications

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“…In a previous phase I study, we demonstrated that a diversified prime/boost regimen using recombinant vaccinia as prime and recombinant fowlpox boost efficiently delivered NY-ESO-1 tumor antigen to the immune system leading to the generation of integrated Ab, CD4 and CD8 T-cell responses (4). In the present report, we tested the clinical efficacy of this approach in two parallel phase II clinical trials focusing on ovarian cancer and melanoma, two cancer types where patients treated for advanced disease are at extremely high risk for recurrence/progression (70% and 80%, respectively) (7,8). Therefore, vaccine strategies to extend remission and disease control rates in these patients are highly desirable.…”

Section: Discussionmentioning

confidence: 99%

“…Although patients with advanced EOC often achieve complete clinical remission after primary surgery and chemotherapy, the majority ultimately die of recurrent/progressive disease (7). Similarly, patients with stage IV malignant melanoma have a poor prognosis, and those with resected stage III/IV melanoma have a high risk of recurrent/progressive disease (8). Therefore, approaches to minimize the risk of progressive disease and enhance the OS of EOC and melanoma patients are desirable.…”

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confidence: 99%

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Efficacy of vaccination with recombinant vaccinia and fowlpox vectors expressing NY-ESO-1 antigen in ovarian cancer and melanoma patients

Odunsi

Matsuzaki

Karbach

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

178

130

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Recombinant poxviruses (vaccinia and fowlpox) expressing tumorassociated antigens are currently being evaluated in clinical trials as cancer vaccines to induce tumor-specific immune responses that will improve clinical outcome. To test whether a diversified prime and boost regimen targeting NY-ESO-1 will result in clinical benefit, we conducted two parallel phase II clinical trials of recombinant vaccinia-NY-ESO-1 (rV-NY-ESO-1), followed by booster vaccinations with recombinant fowlpox-NY-ESO-1 (rF-NY-ESO-1) in 25 melanoma and 22 epithelial ovarian cancer (EOC) patients with advanced disease who were at high risk for recurrence/progression. Integrated NY-ESO-1-specific antibody and CD4 + and CD8 + T cells were induced in a high proportion of melanoma and EOC patients. In melanoma patients, objective response rate [complete and partial response (CR+PR)] was 14%, mixed response was 5%, and disease stabilization was 52%, amounting to a clinical benefit rate (CBR) of 72% in melanoma patients. The median PFS in the melanoma patients was 9 mo (range, 0-84 mo) and the median OS was 48 mo (range, 3-106 mo). In EOC patients, the median PFS was 21 mo (95% CI, 16-29 mo), and median OS was 48 mo (CI, not estimable). CD8 + T cells derived from vaccinated patients were shown to lyse NY-ESO-1-expressing tumor targets. These data provide preliminary evidence of clinically meaningful benefit for diversified prime and boost recombinant pox-viral-based vaccines in melanoma and ovarian cancer and support further evaluation of this approach in these patient populations.effector function | T cell epitopes T he ability to induce robust clonal expansion and effector and memory differentiation of antigen-specific T cells is an important goal of cancer vaccines. To achieve this goal, several approaches have been used in clinical cancer vaccine studies. Although promising results on prolongation of overall survival (OS) have been reported in recent cancer vaccine studies (1), the optimal strategy for generating integrated Ab, CD4, and CD8 responses with potential to control tumor growth has yet to be determined. In this regard, the use of recombinant orthopox vectors such as vaccinia or avipox (fowlpox and/or canarypox) has been shown to induce more robust T-cell responses to tumor antigens (TAs) in animal models and humans, compared with the use of the TA protein in adjuvant (2).Our group has focused on the "cancer-testis" antigen NY-ESO-1, as a prototype tumor antigen for human cancer vaccine studies because of its unique characteristics of tissue restricted expression and inherent immunogenicity (3). We have assessed the immunogenicity of NY-ESO-1-based candidate vaccines in early-phase clinical trials under the sponsorship of the Cancer Vaccine Collaborative (4-6). In a previous pilot study, we tested priming immunization with recombinant vaccinia-NY-ESO-1 (rV-NY-ESO-1), followed by booster vaccinations with recombinant fowlpox-NY-ESO-1 (rF-NY-ESO-1) in patients with various advanced solid tumors (4). We demonstrated that rV-NY-ESO-1 ...

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Efficacy of vaccination with recombinant vaccinia and fowlpox vectors expressing NY-ESO-1 antigen in ovarian cancer and melanoma patients

Odunsi

Matsuzaki

Karbach

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

178

130

View full text Add to dashboard Cite

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“…Chemotherapy with dacarbacine (DTIC) does actually apply as the standard treatment regimen in metastasized melanoma, with reported response rates of only 10% to 18% (1). Even these might be overestimated, as recent studies using new standardized evaluation criteria (2) revealed much lower response rates of 6% to 7% (3,4).…”

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confidence: 99%

In vitro Drug Sensitivity Predicts Response and Survival after Individualized Sensitivity-Directed Chemotherapy in Metastatic Melanoma: A Multicenter Phase II Trial of the Dermatologic Cooperative Oncology Group

Ugurel

Schadendorf

Pföhler

et al. 2006

Clinical Cancer Research

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Purpose: In vitro sensitivity assays are promising tools to predict the individual outcome of different chemotherapy regimens. However, a direct association between in vitro and in vivo chemosensitivity has to be shown by clinical studies. This multicenter phase II trial was aimed to investigate the efficacy of a sensitivity-directed, first-line chemotherapy in metastasized melanoma patients, and to prove an association between in vitro sensitivity and therapy outcome. Patients and Methods: The primary study end point was objective response; secondary end points were safety, overall survival, and progression-free survival.Viable tumor cells obtained from metastatic lesions were tested for chemosensitivity to seven single drugs and five drug combinations using an ATP-based luminescence viability assay. Results: Out of 82 recruited patients (intention-to-treat), 57 received assay-directed chemotherapy and 53 were evaluable for all study end points (per protocol). The drug combinations used were gemcitabine + treosulfan, paclitaxel + cisplatin, paclitaxel + doxorubicin, and gemcitabine + cisplatin. The per protocol population could be divided into 22 (42%) chemosensitive and 31 (58%) chemoresistant patients by an arbitrary chemosensitivity index. Objective response was 36.4% in chemosensitive patients compared with 16.1% in chemoresistant patients (P = 0.114); progression arrest (complete response + partial response + stable disease) was 59.1% versus 22.6% (P = 0.01). Chemosensitive patients showed an increased overall survival of 14.6 months compared with 7.4 months in chemoresistant patients (P = 0.041). Conclusion: In vitro chemosensitivity testing may be worthy of further exploration to see if it could be a useful tool to predict the outcome of melanoma patients treated with a sensitivitydirected chemotherapy. Therefore, these preliminary results will be evaluated by a planned phase III trial using a randomized, standard-regimen controlled setting.Melanoma is a cutaneous neoplasm known for its high aggressiveness, its early dissemination of metastases, and its poor prognosis once metastasized. Chemotherapy with dacarbacine (DTIC) does actually apply as the standard treatment regimen in metastasized melanoma, with reported response rates of only 10% to 18% (1). Even these might be overestimated, as recent studies using new standardized evaluation criteria (2) revealed much lower response rates of 6% to 7% (3, 4). This poor outcome does not rely on an impaired penetration of chemotherapeutics into the tumor, but has been proposed to be caused by chemoresistance mechanisms intrinsic to melanoma cells (5, 6). Moreover, biochemotherapy and immunotherapy regimens did not prove to be superior to DTIC (1, 7).Due to this unfavorable situation, a number of nonstandard chemotherapeutics were tested in small pilot studies to prove a stronger efficacy in melanoma. Although complete remissions of metastatic lesions could only be observed in few patients

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“…Until 2011, if a patient wasn't fit enough to tolerate high dose Interleukin-2 (IL-2), the clinical armamentarium for unresectable/metastatic melanoma was restricted solely to cytotoxic chemotherapy (such as taxanes and alkylating agents) with response rates lower than 20% and no proven gain in survival [5]. Fortunately, after the publication of the watershed phase 3 trial by Drs Hodi and O'day, comparing ipilimumab alone or combined with a gp100 vaccine to the vaccine isolated after failure to previous systemic treatment that showed an overall survival advantage for the 2 experimental arms [6], approval of ipilimumab by the U.S. FDA (food and drug administration) ensued and modern immunotherapy has established a central role in the management of metastatic melanoma.…”

Section: Discussionmentioning

confidence: 99%

Sustained Viral Response to Ipilimumab Treatment in a Patient with HCV Chronic Infection and Metastatic Melanoma: A Case Report

Eiger¹,

Mariano²,

Taranto³

et al. 2017

JPP

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Abstract:The treatment of metastic melanoma has rapidly evolved in the last 5 years, giving clinicians and patients the hope for long lasting responses. In the field of modern immunotherapy, we are reaching the point of an expressive percentage of patients achieving long term survival with anti-CTLA4 and anti-PD1 checkpoint inhibitors. Of note, there is a considerable amount of patients excluded from the checkpoint blockade trials because of comorbidities like chronic viral infections. A precaution to avoid autoimmune induced hepatitis rendered HBV (hepatitis B virus) and HCV (hepatitis C virus) infected patients usually ineligible, but real life data in those patients, who are getting treatment despite of that, is pointing toward the feasibility and safety of immunotherapy in this context. To ilustrate that, we report the case of a metastatic non-BRAF mutated melanoma patient with HCV chronic infection and a surprising benefit derived from ipilimumab and pembrolizumab for his latter condition.

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Systemic treatments for metastatic cutaneous melanoma

Cited by 86 publications

References 15 publications

Efficacy of vaccination with recombinant vaccinia and fowlpox vectors expressing NY-ESO-1 antigen in ovarian cancer and melanoma patients

Efficacy of vaccination with recombinant vaccinia and fowlpox vectors expressing NY-ESO-1 antigen in ovarian cancer and melanoma patients

In vitro Drug Sensitivity Predicts Response and Survival after Individualized Sensitivity-Directed Chemotherapy in Metastatic Melanoma: A Multicenter Phase II Trial of the Dermatologic Cooperative Oncology Group

Sustained Viral Response to Ipilimumab Treatment in a Patient with HCV Chronic Infection and Metastatic Melanoma: A Case Report

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