Evaluation of patients with surgically resected high-risk melanoma receiving adjuvant therapy in routine clinical practice in the United States.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 9577-9577
Author(s):  
Michael B. Atkins ◽  
Cristina Julian ◽  
Matthew H. Secrest ◽  
Janet Lee ◽  
Ana Maria Abajo Guijarro ◽  
...  
Keyword(s):  
Adjuvant Therapy ◽  
Checkpoint Inhibitors ◽  
The United States ◽  
Distant Recurrence ◽  
Advanced Melanoma ◽  
Stage Iii ◽  
Braf Mutations ◽  
Stage Iii Melanoma ◽  
Resected Stage ◽  
Braf Mutant

9577 Background: The management of patients with resected stage III melanoma has changed in recent years, and real-world data on recurrence patterns and adjuvant therapy responses are scarce. This study assessed adjuvant treatment patterns and outcomes in patients with advanced melanoma by BRAF status and relapse location. Methods: Patients diagnosed with stage III advanced melanoma between January 2011 and February 2020 in the nationwide Flatiron Health electronic health record–derived deidentified database were included if they were ≥18 years, received approved first-line (1L) adjuvant therapy after January 2018 with checkpoint inhibitors (CPIs; eg, nivolumab, pembrolizumab) or targeted therapies (TTs; eg, dabrafenib/trametinib), had 6 months’ follow-up and had ≥1 visit after starting adjuvant therapy (Cohort 1). Patients from Cohort 1 were included in Cohort 2 if they had a recurrence following initiation of adjuvant therapy, and those from Cohort 2 were included in Cohort 3 if they had a distant recurrence and available documented BRAF status at any time. Time to next systemic treatment (TTNT), overall survival (OS) and relapse free survival (RFS) were estimated using Kaplan-Meier (KM) methods from adjuvant therapy start (Cohort 1), first recurrence date (Cohort 2) or first distant recurrence date (Cohort 3). Results: Cohort 1 included 447 patients receiving 1L adjuvant therapy; Cohort 2 included patients after first distant (n = 47) or local (n = 35) relapse; Cohort 3 included distant-recurrent patients with tumors that were BRAF wild type (WT) (n = 22) or BRAF mutant (n = 23). The majority of patients were aged < 65 years. Across cohorts, relative use of TTs vs CPIs was similar: Cohort 1 (4.5% vs 96%), Cohort 2 (2.4% vs 98%) and Cohort 3 (2.2% vs 98%). Nivolumab was the most frequent treatment used across cohorts (84%-88%). In Cohort 1, 1- and 2-year KM probabilities for OS, RFS and TTNT were 93.5%/83.8%, 83.2%/70.6% and 84.0%/62.4%, respectively. In Cohort 2, for patients with local recurrence, 6- and 12-month OS probabilities were 93.4% and 78.8%, respectively, which were substantially higher than those for patients with distant recurrence (64.5% and 46.9%). In Cohort 3, for patients with documented BRAF mutations, 6- and 12-month OS rates from disease recurrence were 79.1% and 49.4%, respectively, which were greater than for those with BRAF-WT tumors (54.1% and 46.3%). Conclusions: Early RFS and OS outcomes for patients with surgically resected Stage III melanoma appear comparable to those reported in randomized clinical studies. The majority of patients with advanced melanoma, including patients who experienced recurrence, initiated treatment with CPIs. OS rates were numerically greater for Cohort 3 patients with BRAF-mutant tumors. Outcomes for patients with distant recurrence after adjuvant therapy remain unfavorable and represent a continued unmet medical need.

scholarly journals Adjuvant therapy with pegylated interferon alfa-2b versus observation alone in resected stage III melanoma: final results of EORTC 18991, a randomised phase III trial

The Lancet ◽  
2008 ◽  
Vol 372 (9633) ◽  
pp. 117-126 ◽  
Author(s):  
Alexander MM Eggermont ◽  
Stefan Suciu ◽  
Mario Santinami ◽  
Alessandro Testori ◽  
Wim HJ Kruit ◽  
...  
Keyword(s):  
Adjuvant Therapy ◽  
Pegylated Interferon ◽  
Interferon Alfa ◽  
Phase Iii ◽  
Stage Iii ◽  
Phase Iii Trial ◽  
Pegylated Interferon Alfa ◽  
Stage Iii Melanoma ◽  
Resected Stage

Ipilimumab versus placebo after complete resection of stage III melanoma: Initial efficacy and safety results from the EORTC 18071 phase III trial.

2014 ◽  
Vol 32 (18_suppl) ◽  
pp. LBA9008-LBA9008 ◽  
Author(s):  
Alexander M. Eggermont ◽  
Vanna Chiarion-Sileni ◽  
Jean Jacques Grob ◽  
Reinhard Dummer ◽  
Jedd D. Wolchok ◽  
...  
Keyword(s):  
Lymph Node ◽  
High Risk ◽  
Adjuvant Therapy ◽  
Complete Resection ◽  
Advanced Melanoma ◽  
Phase Iii ◽  
Stage Iii ◽  
Phase Iii Trial ◽  
Risk Of Recurrence ◽  
Stage Iii Melanoma

LBA9008 Background: Ipilimumab (Ipi), a fully human monoclonal antibody that blocks cytotoxic T-lymphocyte antigen-4 to augment antitumor immune responses, is an approved treatment for advanced melanoma. Here, we report the results of a phase III trial designed to evaluate Ipi as an adjuvant therapy for resected stage III melanoma at high risk of recurrence. Methods: In this randomized, double-blind trial, eligible patients (pts) included those ≥18 yrs of age who underwent complete resection of stage III cutaneous melanoma (excluding lymph node metastasis ≤1 mm or in-transit metastasis). 951 pts were randomized (stratified by stage and region) 1:1 to receive Ipi 10 mg/kg (n=475) or placebo (Pbo, n=476) every 3 wks for 4 doses, then every 3 mos for up to 3 yrs until completion, disease recurrence, or unacceptable toxicity. The primary endpoint was recurrence-free survival (RFS), analyzed on the intent-to-treat population. 512 RFS events (recurrence or death) were needed to provide 90% power to detect an Ipi vs Pbo hazard ratio (HR) of 0.75 (2-sided α=5%). Results: Overall, 20%/44%/36% of pts had stage IIIA/IIIB/IIIC, 42% ulcerated primary, and 58% macroscopic lymph node involvement. At a median follow-up of 2.7 yrs, Ipi significantly improved RFS vs Pbo. RFS benefit was consistent across subgroups (e.g., stage IIIB or IIIC, ulcerated primary). Most common grade 3/4 immune-related adverse events (irAEs) in the Ipi and Pbo arms were gastrointestinal (15.9% vs 0.8%), hepatic (10.6% vs 0.2%), and endocrine (8.5% vs 0%). Most irAEs were managed and resolved using established algorithms. Of 471 pts who started Ipi, 245 (52%) discontinued treatment due to AEs [182 (38.6%) within 12 weeks]; 5 (1.1%) died due to drug-related AEs. Conclusions: In this phase III trial, Ipi as adjuvant therapy provided a clinically and statistically significant improvement in RFS vs Pbo for pts with stage III melanoma at high risk of recurrence. AE profile was generally consistent with that observed in advanced melanoma, although with a higher incidence of endocrinopathies. Clinical trial information: NCT00636168. EudraCT Number: 2007-001974-10. [Table: see text]

Facility contextual effects influence the use of adjuvant immunotherapy in stage III melanoma.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e18758-e18758
Author(s):  
Laura D. Leonard ◽  
Robert J. Torphy ◽  
Laurel Beaty ◽  
Thiago B. de Araujo ◽  
Kathryn Colborn ◽  
...  
Keyword(s):  
Checkpoint Inhibitors ◽  
Private Insurance ◽  
Contextual Effects ◽  
Mitotic Rate ◽  
Stage Iii ◽  
Adjuvant Immunotherapy ◽  
Random Intercept ◽  
Patient Goals ◽  
Stage Iii Melanoma ◽  
Resected Stage

e18758 Background: There are now numerous effective adjuvant immunotherapy options for surgically resected stage III melanoma including novel checkpoint inhibitors and targeted therapies. Current guidelines recommend that the decision to treat stage III melanoma with adjuvant immunotherapy should be individualized and based upon disease burden, patient goals and anticipated therapy tolerance. We sought to assess the contribution of patient, tumor and facility factors on the implementation of immunotherapy in patients with surgically resected stage III melanoma. Methods: Using the National Cancer Database (NCDB), patients from 2012-2017 that underwent excision and were found to have a positive sentinel node were identified. A multivariable mixed effects logistic regression model with a random intercept for site was used to determine the effect of patient, tumor, and facility variables on the probability of immunotherapy. Reference Effect Measures (REM) were used to estimate the variation in immunotherapy use due to unmeasured facility factors (contextual effects) after adjusting for measured patient, tumor, and facility variables. Results: From 2012 to 2017, the percent of patients with stage III melanoma treated with adjuvant immunotherapy increased from 23.7% to 38.5% (p < 0.05). Overall, younger patients and patients with private insurance were more likely to receive immunotherapy. Tumor factors associated with increased use of adjuvant immunotherapy included increasing depth, mitotic rate ³1, ulceration, lymphovascular invasion (LVI), and undergoing a completion lymph node dissection (CLND). Additionally, treatment at a facility with a surgical volume <190 cases/year was associated with increased immunotherapy use. However, the width of the 90% REM range for unmeasured facility effects exceeded that of the measured facility, tumor, time, and patient demographics suggesting that contextual effects had a higher contribution to the variation in immunotherapy use. Conclusions: Our analysis suggests that uninsured patients and patients with government insurance (Medicaid and Medicare) are not receiving immunotherapy at the same frequency as privately insured patients with the same tumor characteristics treated at the same facility. Lastly, compared to known patient, tumor and facility factors, institutional contextual effects were the major drivers of the implementation of immunotherapy.[Table: see text]

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