Economic Burden of Adverse Events Associated with Immunotherapy and Targeted Therapy for Metastatic Melanoma in the Elderly.
Am Health Drug Benefits. 2018 Oct;11(7):334-343
Authors: Ghate SR, Li Z, Tang J, Nakasato AR
Background: Immunotherapies and targeted therapies have drastically improved survival in metastatic melanoma, but they can cause a range of adverse events (AEs). Understanding the costs of these events would facilitate an accurate comparison of melanoma treatments.
Objective: To compare the costs and frequency of AEs associated with immunotherapy and with targeted therapy in elderly patients with metastatic melanoma.
Methods: We conducted a retrospective cohort study using Medicare claims data from 2011 to 2014. Patients included had to have ≥1 diagnoses of metastatic melanoma and ≥1 claims for an immunotherapy or targeted therapy. We compared the 30-day expenditures of patients with and without each AE using a generalized linear model to determine the incremental cost per AE in patients who received immunotherapy or targeted therapy. The baseline demographic and clinical differences were adjusted for using propensity score with inverse probability of treatment. We also compared the mean costs of AEs associated with immunotherapy and targeted therapy.
Results: A total of 844 patients were included in the study (mean age, 75 years; standard deviation, 14 years). The mean baseline Charlson Comorbidity Index score was 8.4, and 65% of the patients were male. The mean cost for AEs was highest for respiratory events (ie, $24,150). Gastrointestinal, respiratory, and hematologic AEs were more common in patients who received immunotherapy, whereas general and administration-site AEs and other AEs (eg, fatigue, infections, muscular weakness) were more frequent in patients who received targeted therapy. AE-related costs with immunotherapy were highest for gastrointestinal, respiratory, and pain-related AEs; AEs with targeted therapy were highest for cardiovascular and general and administration-site events.
Conclusion: These findings suggest that incremental costs associated with treatment-related AEs among elderly patients with metastatic melanoma were substantial, but the risks for and costs of the various types of AEs differed by therapy. Understanding the risks for and costs of AEs associated with the various therapeutic options can inform treatment decision-making in elderly patients with metastatic melanoma.
PMID: 30647822 [PubMed]
Validation of Melanoma Immune Profile (MIP), a Prognostic Immune Gene Prediction Score for Stage II-III Melanoma.
Clin Cancer Res. 2019 Jan 15;:
Authors: Gartrell RD, Marks DK, Rizk EM, Bogardus M, Gérard CL, Barker LW, Fu Y, Esancy CL, Li G, Ji J, Rui S, Ernstoff MS, Taback B, Pabla S, Chang R, Lee SJ, Krolewski JJ, Morrison C, Saenger YM
PURPOSE: Biomarkers are needed to stratify patients with stage II-III melanoma for clinical trials of adjuvant therapy because, while immunotherapy is protective, it also confers the risk of severe toxicity. We previously defined and validated a 53-immune gene melanoma immune profile (MIP) predictive both of distant metastatic recurrence (DMR) and of disease-specific survival (DSS). Here, we test MIP on a third independent population.
METHODS: A retrospective cohort of 78 patients with stage II-III primary melanoma was analyzed using the nanoString assay to measure expression of 53 target genes and MIP score was calculated. Statistical analysis correlating MIP with disease-specific survival, overall survival, distant metastatic recurrence, and distant metastasis-free interval was performed using receiver operating characteristic curves, Kaplan-Meier (KM) curves, and standard univariable and multivariable Cox proportional hazards models.
RESULTS: MIP significantly distinguished patients with distant metastatic recurrence from those without distant metastatic recurrence using ROC curve analysis (AUC=0.695, p=0.008). We defined high and low risk groups based on the cutoff defined by this ROC curve and find that MIP correlates with both DSS and OS by ROC curve analysis (AUC=0.719, p=0.004 and AUC=0.698, p=0.004, respectively). Univariable Cox regression reveals that a high-risk MIP score correlates with DSS (p=0.015, HR=3.2).
CONCLUSION: MIP identifies patients with low risk of death from melanoma and may constitute a clinical tool to stratify stage II-III melanoma patients for enrollment in clinical trials.
PMID: 30647081 [PubMed - as supplied by publisher]
UBE2N plays a pivotal role in maintaining melanoma malignancy.
Oncotarget. 2018 Dec 21;9(100):37347-37348
Authors: Dikshit A, Zhang JY
PMID: 30647835 [PubMed]
Immunotherapy comes of age in octagenarian and nonagenarian metastatic melanoma patients.
Eur J Cancer. 2019 Jan 12;108:61-68
Authors: Ben-Betzalel G, Steinberg-Silman Y, Stoff R, Asher N, Shapira-Frommer R, Schachter J, Markel G
Immunotherapy with anti-programmed cell death-1 (PD-1) agents is an effective treatment for metastatic melanoma. Recent data hint at better response to therapy for patients over age 65 years. Patients with metastatic melanoma in their 80's and 90's pose a clinical challenge. We describe a cohort of 144 patients ≥65 years and analyse the efficacy and toxicity of anti-PD-1 therapy in ages 80-100 years compared with ages 65-79 years. Records of metastatic melanoma patients aged 65-100 years treated with anti-PD-1 were collected retrospectively. Baseline parameters, response rate (overall response rate [ORR]), best response, progression-free survival (PFS) and overall survival (OS) and immune-related adverse events were analysed. Cox regression, t test, and chi-square test were used for statistical analysis. Five hundred patients were treated with anti-PD-1 agents between 2013 and 2018.Eighty-two patients were aged 65-79 years (group A, median 71.5 years), and 62 patients were aged 80-100 years (group B, median 84 years, range 80-97 years). Baseline parameters were comparable except for worse PS in group B (p = 0.001). One hundred twenty-four patients were evaluable for analysis of response (76 group A, 48 group B). A trend was noted for higher ORR in the older group with 62.3% for group A and 73.9% for group B (p = 0.09). Complete response was significantly higher in group B versus group A (47.9% versus 20%, p = 0.001). No significant difference was found in PFS or OS between the groups. Toxicity for all patients was similar at 22.8%-25.6% G2-4 adverse events. Elderly patients show enhanced response to anti-PD-1 therapy. Increasing age within the elderly patients group may predict an even better response to therapy and comparable survival in patients of very old age.
PMID: 30648631 [PubMed - as supplied by publisher]
Clinical melanoma characteristics and survival-a single-center retrospective study between 2000 and 2010.
Wien Med Wochenschr. 2019 Jan 16;:
Authors: Feichtenschlager V, Weihsengruber F, Richter L, Vujic I, Rappersberger K, Posch C
The aim of this study was to characterize clinical, histological, and outcome features of primary melanoma in 1329 patients managed at a single-center institution between 2000 and 2010. Parameters included age at diagnosis, sex, tumor location, histology, stage, Breslow thickness, and sentinel lymph node status among others. The mean age at diagnosis was 59.1 ± 16.7 years. Women were significantly younger than men when diagnosed (57.2 vs. 61.0 years; p < 0.001). Most melanomas (83%) were diagnosed on typically sun-exposed skin areas. Superficial spreading melanoma (39.5%) was the most frequent histological subtype. The median Breslow thickness was significantly higher for men compared to women (1.10 mm vs. 0.90 mm; p = 0.018). 38.3% of patients with positive and 12.9% of patients with negative sentinel biopsies progressed. Five-year survival analysis for a sub-cohort of 577 patients showed better 5‑year overall survival for woman compared to men (75.8% vs. 63.6%; p = 0.025). Our findings indicate differences in patient characteristics between men and women, and underscore the importance of early melanoma detection to prevent disease progression.
PMID: 30649651 [PubMed - as supplied by publisher]