0000000000286188
AUTHOR
Lucie Heinzerling
Outcome of melanoma patients with elevated LDH treated with first-line targeted therapy or PD-1-based immune checkpoint inhibition.
Abstract Background Elevated lactate dehydrogenase (LDH) is a known predictive and prognostic factor for a poor outcome in patients with metastatic melanoma. It is unclear whether first-line targeted therapy (TT) or immune checkpoint inhibition (ICI) is more beneficial in melanoma patients with elevated LDH because prospective studies in this area are lacking. Methods This multicentre retrospective cohort study was conducted at 25 melanoma centres worldwide to analyse progression-free survival (PFS) and overall survival (OS) among melanoma patients with elevated LDH. The role of confounders was addressed by using inverse probability of treatment weighting. Results Among 173 BRAFV600-mutant …
Fear of progression in patients with low-risk malignant melanoma.
e21615 Fear of progression in patients with low-risk malignant melanoma Fear of cancer progression (FoP) is one of the problems most commonly reported by cancer patients and is among the most prevalent cancer-related worries in cancer survivors. FCR is highly variable in different cancer entities. Background: This study aimed to elicit the prevalence and significance of FCR in melanoma patients with low risk tumors and further to assess psychosocial and demographic factors predicting severity of FoP as well as to determine the impact of FoP on quality of life (QoL). Methods: In total, 133 patients with low-risk melanoma (pT1a) completed the short version of the Fear of Progression Question…
Willingness to pay for a cure of low-risk melanoma patients in Germany
Malignant melanoma is potentially life-threatening but in most cases curable if detected early. Willingness to pay (WTP) is a preference-based construct that reflects burden of disease by assessment of the monetary value for a hypothetical cure from disease. Since WTP (directly as total amount of money) has not been assessed so far in patients with low risk melanoma, it was interesting to gain insights in this patient population and then, in a second step, compare it directly with the WTP of their treating dermato-oncologists. WTP was assessed in 125 patients with low-risk melanoma and additionally in 105 treating physicians, asking for the one-time and continuous payments they would be wil…
The GERMELATOX DeCOG-trial: Attitude of German melanoma patients towards toxicity during adjuvant interferon treatment-Differences between the patient's and the physician's perspective
e20099 Background: Although trials of adjuvant interferon alfa-2b (IFNa-2b) in high-risk melanoma patients suggest improvement in disease-free survival (DFS), metaanalyses showed only a marginal ov...
Management of side effects of immune checkpoint blockade by anti-CTLA-4 and anti-PD-1 antibodies in metastatic melanoma
CTLA-4 and PD-1 are potential targets for tumor-induced downregulation of lymphocytic immune responses. Immune checkpoint-modifying monoclonal antibodies oppose these effects, inducing T cell-mediated immune responses to various tumors including melanoma. Both anti-CTLA-4 and anti-PD-1 antibodies modify the interaction between tumor, antigen-presenting cells, and T lymphocytes. With respect to overall survival, clinical studies have shown a major benefit for the anti-CTLA-4 antibody ipilimumab as well as the two anti-PD-1 antibodies nivolumab and pembrolizumab. Following approval of ipilimumab in 2011, the latter two achieved market authorization in the summer of 2015. Immune responses thus…
Impact of a preceding radiotherapy on the outcome of immune checkpoint inhibition in metastatic melanoma: a multicenter retrospective cohort study of the DeCOG
BackgroundImmune checkpoint inhibition (ICI) is an essential treatment option in melanoma. Its outcome may be improved by a preceding radiation of metastases. This study aimed to investigate the impact of a preceding radiotherapy on the clinical outcome of ICI treatment.MethodsThis multicenter retrospective cohort study included patients who received anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) or anti-programmed cell death protein 1 (PD-1) ICI with or without preceding radiotherapy for unresectable metastatic melanoma. ICI therapy outcome was measured as best overall response (BOR), progression-free (PFS) and overall survival (OS). Response and survival analyses were adjusted …
A multicenter DeCOG study on predictors of vemurafenib therapy outcome in melanoma: pretreatment impacts survival
Background: Kinase inhibitors targeting the BRAF V600 mutation have become standard in the treatment of metastatic melanoma. Albeit in wide clinical use, the patterns associated with therapy outcome are not fully elucidated. The present study was aimed to identify predictive factors of therapy response and survival under the BRAF inhibitor vemurafenib. Patients and methods: This multicenter retrospective study analyzed patient, tumor, and pretreatment characteristics collected in BRAF V600-mutated stage IV melanoma patients before single-agent therapy with the BRAF inhibitor vemurafenib. Results: A total of 300 patients from 14 centers were included into this study with a median follow-up t…
Immune checkpoint inhibition therapy for advanced skin cancer in patients with concomitant hematological malignancy: a retrospective multicenter DeCOG study of 84 patients
BackgroundSkin cancers are known for their strong immunogenicity, which may contribute to a high treatment efficacy of immune checkpoint inhibition (ICI). However, a considerable proportion of patients with skin cancer is immuno-compromised by concomitant diseases. Due to their previous exclusion from clinical trials, the ICI treatment efficacy is poorly investigated in these patients. The present study analyzed the ICI treatment outcome in advanced patients with skin cancer with a concomitant hematological malignancy.MethodsThis retrospective multicenter study included patients who were treated with ICI for locally advanced or metastatic melanoma (MM), cutaneous squamous cell carcinoma (cS…
Side effect management during immune checkpoint blockade using CTLA-4 and PD-1 antibodies for metastatic melanoma – an update
CTLA-4 and PD-1 play a key role in tumor-induced downregulation of lymphocytic immune responses. Immune checkpoint inhibitors have been shown to alter the immune response to various cancer types. Anti-CTLA-4 and anti-PD-1 antibodies affect the interaction between tumor, antigen-presenting cells and T lymphocytes. Clinical studies of the anti-CTLA-4 antibody ipilimumab and the anti-PD-1 antibodies nivolumab and pembrolizumab have provided evidence of their positive effects on overall survival in melanoma patients. Combined treatment using ipilimumab and nivolumab has been shown to achieve five-year survival rates of 52 %. Such enhancement of the immune response is inevitably associated with …
Lipase elevation and type 1 diabetes mellitus related to immune checkpoint inhibitor therapy – A multicentre study of 90 patients from the German Dermatooncology Group
Abstract Aim Immune checkpoint inhibition (ICI) triggers immune-related adverse events (irAEs). The relevance of lipase elevation remains unclear. Patients and methods Skin cancer patients with newly detected serum lipase elevation (at least twofold upper normal limit) or newly diagnosed type I diabetes mellitus upon ICI therapy were retrospectively collected at 14 German skin cancer centres. Results We identified 68 patients with lipase elevation occurring after a median time of 19 (range 1–181) weeks on ICI, 15 (22%) thereof had symptoms consistent with pancreatitis. Forty-seven patients (73%) had other irAE, mainly colitis. Discontinuation (n = 24, 35%) or interruption (n = 26, 38%) of I…
Hematological immune related adverse events after treatment with immune checkpoint inhibitors
Abstract Introduction With the increasing use of checkpoint inhibitors, rare immune-related adverse events (irAE) are being identified. Haematological irAE (hem-irAE) are difficult to treat and have shown high mortality rates. In order to improve side-effect management for these potentially life-threatening events, we analysed frequency, severity and outcomes. Patients and methods Patients who developed hem-irAE while being treated with immune checkpoint inhibitors (ICI) therapy were retrospectively identified from 18 international cancer centres. Results In total, more than 7626 patients treated with ICI were screened, and 50 patients with hem-irAE identified. The calculated incidence amou…
Fear of cancer progression in patients with stage IA malignant melanoma.
We aimed to determine the prevalence and importance of fear of cancer progression (FoP) in melanoma patients with stage IA tumours to assess psychosocial and demographic factors associated with severity of FoP and to determine the relationship of FoP and quality of life (QoL). One hundred and thirty-six patients with stage IA melanoma completed the short version of the Fear of Progression Questionnaire (FoP-Q-SF), the Hospital Anxiety and Depression Scale (HADS) and the EORTC-QLQ-C30. We found a mean FoP-Q-SF sum score of 30.2 points (±8.4 points SD). In this study, 33% of patients reported high FoP at or above the cutoff-value of 34 points. Higher FoP was found in women (p < 0.01), young (…
Clinical outcome of concomitant vs interrupted BRAF inhibitor therapy during radiotherapy in melanoma patients
Background: Concomitant radiation with BRAF inhibitor (BRAFi) therapy may increase radiation-induced side effects but also potentially improve tumour control in melanoma patients. Methods: A total of 155 patients with BRAF-mutated melanoma from 17 European skin cancer centres were retrospectively analysed. Out of these, 87 patients received concomitant radiotherapy and BRAFi (59 vemurafenib, 28 dabrafenib), while in 68 patients BRAFi therapy was interrupted during radiation (51 vemurafenib, 17 dabrafenib). Overall survival was calculated from the first radiation (OSRT) and from start of BRAFi therapy (OSBRAFi). Results: The median duration of BRAFi treatment interruption prior to radiothera…