Use of immunotherapy for stage-III and IV melanoma and likelihood of regional and distant lymph node resection and surgical resection for distant metastasis.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 9558-9558
Author(s):  
George Molina ◽  
Gyulnara G. Kasumova ◽  
Motaz Qadan ◽  
Genevieve Marie Boland
Keyword(s):  
Lymph Node ◽  
Surgical Resection ◽  
Stage Iv ◽  
Stage Iii ◽  
Median Income ◽  
Adjusted Relative Risk ◽  
Facility Type ◽  
Stage Iii Melanoma ◽  
Stratified Analysis ◽  
Stage Iv Melanoma

9558 Background: Immunotherapy (IMT) for stages-III and IV melanoma has dramatically changed overall prognosis and treatment strategies. The aim of this study was to evaluate if use of IMT significantly changed the likelihood of regional/distant lymph node (LN) resection and surgical resection for distant metastases (DM) among patients with stages-III and IV melanoma, respectively, in the pre- and post-2011 era. Methods: The National Cancer Database (2004-2015) was used to evaluate the likelihood of regional/distant LN resection and surgical resection for DM among patients with stages-III and IV melanoma, respectively, with use of IMT. Multivariable stepwise with forward selection Poisson regression with robust standard errors was used to adjust for potential confounders (age, gender, race, year of diagnosis, Charlson-Deyo Score, facility type, facility location, insurance status, 2012 median income quartile, and 2013 urban/rural status). A stratified analysis was performed to evaluate differences among facility type. Results: There were 28,847 patients (median age 62 (IQR 53-73); 36.3% female) with stage-III melanoma and 14,443 patients (median age 66 (IQR 56-76); 31.7% female) with stage-IV melanoma. Overall, 24.3% (n = 7,018) and 17.0% (n = 2,459) with stage-III and IV melanoma, respectively, received IMT. The adjusted relative risk (aRR) of regional/distant LN resection among patients with stage-III melanoma was significantly higher with use of IMT (aRR 1.16, 95% CI 1.05–1.28, P = 0.004), while the aRR of surgical resection for DM was significantly lower with use of IMT for stage-IV melanoma (aRR 0.85, 95% CI 0.78–0.92, P < 0.001). Stratified analysis demonstrated that the findings were principally reflective of academic/research hospitals. Conclusions: The higher likelihood of regional/distant LN resection in stage-III melanoma may be due to the curative role of surgery and preceded the post-MSLT-II era. Conversely, in stage-IV melanoma, surgery may be limited to resectable oligometastatic disease given the durable and systemic benefit of first-line IMT.

Surgical Management of Melanoma and Other Skin Cancers

2015 ◽  
Author(s):  
Jennifer A. Wargo ◽  
Kenneth Tenabe
Keyword(s):  
Lymph Node ◽  
Surgical Treatment ◽  
Skin Cancer ◽  
Cell Carcinoma ◽  
Stage Iv ◽  
Stage Iii ◽  
Non Melanoma Skin Cancer ◽  
Skin Cancers ◽  
Stage Iv Melanoma ◽  
Melanoma Skin

The prevalence of malignant skin cancers has increased significantly over the past several years. Approximately 1.2 million cases of non-melanoma skin cancer are diagnosed per year. More alarming, up to 80,000 cases of melanoma are diagnosed per year, an incidence that has been steadily increasing, with a lifetime risk of 1 in 50 for the development of melanoma. The disturbing increase in the incidence of both non-melanoma skin cancer and melanoma can largely be attributed to the social attitude toward sun exposure. The clinical assessment and management of skin lesions can be challenging. This review describes the assessment process, including thorough history and examination; the need for possible biopsy; and excision criteria. Specific types of skin cancer are distinguished and include basal cell carcinoma; squamous cell carcinoma; and melanoma; and for each type the incidence; epidemiology; histologic subtypes; diagnosis; and both surgical and non-surgical treatments are provided. Stages I-IV of melanoma are detailed, with prognostic factors described. Surgical treatment for stages I and II include description of the margins of excision and sentinel lymph node biopsy. The surgical treatment of Stage III melanoma further includes therapeutic lymph node dissection and isolated limb perfusion. Adjuvant therapies are also presented and include radiotherapy and chemotherapy. The additional treatment of metastasectomy for Stage IV melanoma is described. For both Stage III and IV melanoma, the study of vaccines to host immune cells is reported. For Stage IV melanoma, the text also describes immunotherapy treatment. Operative procedures specific to superficial and deep groin dissections are outlined. This review contains 9 figures, 3 tables, and 96 references.

Personalized response-driven adjuvant therapy after combination ipilimumab and nivolumab in high-risk resectable stage III melanoma: PRADO trial.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. TPS9605-TPS9605 ◽  
Author(s):  
Irene Reijers ◽  
Elisa A. Rozeman ◽  
Alexander M. Menzies ◽  
Bart A. Van De Wiel ◽  
Hanna Eriksson ◽  
...  
Keyword(s):  
Lymph Node ◽  
Stage Iv ◽  
Pathologic Response ◽  
Pathological Response ◽  
Stage Iii ◽  
Phase 2 ◽  
Primary Endpoints ◽  
Phase 1B ◽  
Stage Iii Melanoma

TPS9605 Background: Adjuvant (adj) immune checkpoint inhibition (ICI) improves relapse free survival (RFS) in stage III melanoma patients (pts). However, preclinical and translational data suggest that neo-adjuvant (neoadj) treatment might be favorable due to broader immune activation. The phase 1b OpACIN study comparing neoadj to adj IPI plus NIVO demonstrated a high pathological response rate (pRR) of 78% complicated by 90% gr 3-4 immune-related adverse events (irAEs). The phase 2 OpACIN-neo trial tested safety and efficacy of three different schemes of neoadj IPI+NIVO and identified two cycles of IPI 1mg/kg + NIVO 3mg/kg as well tolerated (20% gr 3-4 irAEs), with a high pRR of 77%. In both trials, none of the pts with a pathologic response have relapsed after a median follow-up of 30 and 8.3 months. In stage IV melanoma, long-term benefit is observed in patients achieving CR with ICI, even after cessation of therapy. This raises the question of whether a therapeutic lymph node dissection (TLND) can be omitted when a deep pathologic response with neoadj IPI+NIVO is achieved. Methods: The aim of this international multi-center investigator-initiated phase 2 PRADO extension study is to confirm the pRR and toxicity of 2 cycles of neoadjuvant IPI 1mg/kg + NIVO 3mg/kg (the preferred OPACIN-neo regimen) and to test response-driven subsequent therapy i.e. omitting surgery and adjuvant ICI based on the pathological response. 100-110 pts with stage IIIB/C melanoma and a measurable lymph node (≥15mm according to RECIST 1.1) will receive two cycles of IPI 1mg/kg + NIVO 3mg/kg after marker placement into the largest lymph node metastasis. After six weeks, pts will undergo resection of the index lymph node. For pCR/near pCR, pts will not undergo TLND; For pPR, pts will undergo TLND; and for pNR, pts will undergo TLND and start adjuvant NIVO or targeted therapy +/- radiotherapy for 52 weeks. Primary endpoints are pRR of marked lymph node and RFS at 24 months. Baseline biopsies, blood samples (week 0, 6, 12) and faeces (week 0, 6) will be collected for translational research analyses. The first patient in this trial was included in October 2018; 22 patients have been enrolled. Clinical trial information: NCT02977052.

Incidence of New Primary Melanomas After Diagnosis of Stage III and IV Melanoma

2014 ◽  
Vol 32 (8) ◽  
pp. 816-823 ◽  
Author(s):  
Lisa Zimmer ◽  
Lauren E. Haydu ◽  
Alexander M. Menzies ◽  
Richard A. Scolyer ◽  
Richard F. Kefford ◽  
...  
Keyword(s):  
Cumulative Incidence ◽  
Braf Inhibitor ◽  
Stage Iv ◽  
Incidence Rates ◽  
Stage Iii ◽  
Prior History ◽  
Braf Inhibitors ◽  
History Of ◽  
Stage Iii Melanoma ◽  
Stage Iv Melanoma

Purpose New primary melanomas (NPMs) have developed in some patients with metastatic melanoma treated with BRAF inhibitors. We sought to determine the background incidence of spontaneous NPMs after a diagnosis of American Joint Committee on Cancer/International Union Against Cancer stage III or IV melanoma in patients not treated with a BRAF inhibitor. Patients and Methods Patients diagnosed with stage III or IV melanoma at Melanoma Institute Australia between 1983 and 2008 were analyzed, and those who received a BRAF inhibitor were excluded. Results Two hundred twenty-nine (5%) of 4,215 patients with stage III melanoma and 43 (1%) of 3,563 patients with stage IV melanoma had at least one NPM after diagnosis of stage III or IV disease. The 6-month, 1-year, and 10-year cumulative incidence rates of developing an NPM after stage III melanoma were 1.2% (95% CI, 0.86% to 1.51%), 1.8% (95% CI, 1.44% to 2.26%), and 5.9% (95% CI, 5.08% to 6.74%), respectively. The 3-month, 6-month, and 1-year cumulative incidence rates of NPM after diagnosis of stage IV melanoma were 0.2% (95% CI, 0.07% to 0.36%), 0.3% (95% CI, 0.15% to 0.51%), and 0.4% (95% CI, 0.25% to 0.7%), respectively. In both patients with stage III and stage IV melanoma, male patients and patients with a prior history of multiple primaries had a higher incidence of NPM. Conclusion Patients with stage III and stage IV melanoma remain at risk for development of further primary melanomas, particularly if they have a history of multiple primary melanomas before stage III or IV disease. The incidence rates are lower than those reported in patients receiving BRAF inhibitors. However, the results must be compared with caution because dermatologic assessment is more frequent in BRAF inhibitor trials.

scholarly journals 300 Final analysis of a prospective, randomized, double-blind, placebo-controlled phase IIb trial of tumor lysate, particle-loaded, dendritic cell vaccine in stage III/IV melanoma: 36-month analysis

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A327-A327
Author(s):  
Lexy Adams ◽  
Robert Chick ◽  
Guy Clifton ◽  
Timothy Vreeland ◽  
Patrick McCarthy ◽  
...  
Keyword(s):  
Disease Free Survival ◽  
Stage Iv ◽  
Standard Of Care ◽  
Stage Iii ◽  
Tumor Lysate ◽  
Double Blind ◽  
Free Survival ◽  
Resected Stage ◽  
Disease Free ◽  
Stage Iv Melanoma

BackgroundThe tumor lysate, particle-loaded, dendritic cell (TLPLDC) vaccine is created ex vivo by loading autologous dendritic cells (DC) with yeast cell wall particles (YCWP) containing autologous tumor lysate, thus delivering tumor antigens to the DC cytoplasm via phagocytosis. TLPLDC then activates a robust T cell response against the unique antigens for each patient. The primary analysis of the prospective, randomized, multi-center, double-blind, placebo-controlled phase IIb trial in patients with resected stage III/IV melanoma showed TLPLDC improved 24-month disease-free survival (DFS) in the per-treatment (PT) analysis (patients completing the 6-month primary vaccine series). Here, we examine the secondary endpoint of 36-month DFS and overall survival (OS).MethodsPatients with resected stage III/IV melanoma were randomized 2:1 to TLPLDC vaccine or placebo (autologous DC loaded with empty YCWP). Treatments were given at 0, 1, 2, 6, 12 and 18 months. The protocol was amended to include patients receiving concurrent checkpoint inhibitors (CPIs) to follow changes in standard of care. The co-primary endpoints were 24-month DFS by intention-to-treat (IT) analysis and per-treatment (PT) analysis, with secondary endpoints including 36-month DFS and OS by ITT and PT analysis, pre-specified analysis by stage, and safety as measured by CTCAE v4.03.ResultsOverall, 103 patients received TLPLDC and 41 placebo. In PT analysis, 65 patients received TLPLDC and 32 placebo. Total adverse events (AEs), grade 3+ AEs, and serious AEs (SAEs) were similar in placebo vs TLPLDC groups, with one related SAE per treatment arm. By ITT analysis, 36-month OS was 76.2% for TLPLDC vs 70.3% for placebo (HR 0.72, p=0.437) and 36-month DFS was 35.6% vs 27.1% (HR 0.95, p=0.841). By PT analysis, 36-month DFS was improved with TLPLDC (57.5% vs 35.0%; HR 0.50, p=0.025, figure 1). This effect was even more dramatic in resected stage IV patients (36-month DFS: 60.9% vs 0%; HR 0.12, p=0.001, figure 2).ConclusionsThis phase IIb trial again demonstrates the safety of the TLPLDC vaccine, and an improved 36-month DFS in patients with resected stage III/IV melanoma who complete the primary vaccine series, particularly in the stage IV subgroup. Next, a phase III trial will evaluate the efficacy of TLPLDC vaccine as adjuvant treatment for resected stage IV melanoma, with patients randomized to receive standard of care PD-1 inhibitors + TLPLDC versus PD-1 inhibitors + placebo.Abstract 300 Figure 136-month disease free survival for patients receiving TLPLDC vs placebo by PT analysisAbstract 300 Figure 236-month disease free survival for subset of stage IV melanoma patients receiving TLPLDC vs placebo by PT analysisTrial RegistrationThis is a phase IIb clinical trial registered under NCT02301611Ethics ApprovalThis study was approved by Western IRB, protocol 20141932.

scholarly journals Completely resected stage III melanoma controversy - 15 years of national tertiary centre experience

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Barbara Peric ◽  
Sara Milicevic ◽  
Andraz Perhavec ◽  
Marko Hocevar ◽  
Janez Zgajnar
Keyword(s):  
Lymph Node ◽  
Sentinel Lymph Node ◽  
Rapid Development ◽  
Primary Tumour ◽  
Stage Iii ◽  
Unknown Primary ◽  
Tertiary Centre ◽  
Kaplan Meier ◽  
Stage Iii Melanoma ◽  
Resected Stage

AbstractBackgroundTwo prospective randomized studies analysing cutaneous melanoma (CM) patients with sentinel lymph node (SLN) metastases and rapid development of systemic adjuvant therapy have changed our approach to stage III CM treatment. The aim of this study was to compare results of retrospective survival analysis of stage III CM patients’ treatment from Slovenian national CM register to leading international clinical guidelines.Patients and methodsSince 2000, all Slovenian CM patients with primary tumour ≥ TIb are treated at the Institute of Oncology Ljubljana and data are prospectively collected into a national CM registry. A retrospective analysis of 2426 sentinel lymph node (SLN) biopsies and 789 lymphadenectomies performed until 2015 was conducted using Kaplan-Meier survival curves and log-rank tests.ResultsPositive SLN was found in 519/2426 (21.4%) of patients and completion dissection (CLND) was performed in 455 patients. The 5-year overall survival (OS) of CLND group was 58% vs. 47% of metachronous metastases group (MLNM) (p = 0.003). The 5-year OS of patients with lymph node (LN) metastases and unknown primary site (UPM) was 45% vs. 21% of patients with synchronous LN metastasis. Patients with SLN tumour burden < 0.3 mm had 5-year OS similar to SLN negative patients (86% vs. 85%; p = 0.926). The 5-year OS of patients with burden > 1.0 mm was similar to the MLNM group (49% vs. 47%; p = 0.280).ConclusionsStage III melanoma patients is a heterogeneous group with significant OS differences. CLND after positive SLNB might still remain a method of treatment for selected patients with stage III.

Surgical Management of Advanced Adrenocortical Carcinoma: A 21-year Population-based Analysis

2013 ◽  
Vol 79 (10) ◽  
pp. 1115-1118 ◽  
Author(s):  
Thuy B. Tran ◽  
Douglas Liou ◽  
Vijay G. Menon ◽  
Nicholas N. Nissen
Keyword(s):  
Surgical Resection ◽  
Adrenocortical Carcinoma ◽  
Univariate Analysis ◽  
Survival Rates ◽  
Stage Iv ◽  
Population Based ◽  
Stage Iii ◽  
Dismal Prognosis ◽  
Advanced Stages ◽  
The Impact

Adrenocortical carcinoma (ACC) is a rare endocrine malignancy with a dismal prognosis. When diagnosed in advanced stages of the disease, the outcomes of surgical resection are not well understood. The objective of this study is to determine the impact of surgery in patients with advanced ACC. Using the Surveillance, Epidemiology and End Results database, we identified patients diagnosed with Stage III and IVACC between 1988 and 2009. A total of 320 patients with Stage III and IV disease were included in our analysis. In patients treated with surgical resection, the Stage III 1- and 5-year survival rates were 77 and 40 per cent, respectively, whereas the Stage IV 1- and 5-year survival rates were 54 and 27.6 per cent, respectively. Patients treated without surgery had poor survival at 1 year for both Stage III (13%) and Stage IV (16%) ( P < 0.01 compared with the surgical groups). Lymph node dissection was performed in 26 per cent of the patients with advanced ACC and was associated with improved survival in univariate analysis of Stage IV patients. Overall, our results indicate that favorable survival outcomes can be achieved even in patients with Stage III and IV disease and surgery should be considered in patients with advanced ACC.

scholarly journals Longer Follow-Up Confirms Recurrence-Free Survival Benefit of Adjuvant Pembrolizumab in High-Risk Stage III Melanoma: Updated Results From the EORTC 1325-MG/KEYNOTE-054 Trial

2020 ◽  
Vol 38 (33) ◽  
pp. 3925-3936 ◽  
Author(s):  
Alexander M. M. Eggermont ◽  
Christian U. Blank ◽  
Mario Mandala ◽  
Georgina V. Long ◽  
Victoria G. Atkinson ◽  
...  
Keyword(s):  
Lymph Node ◽  
High Risk ◽  
Phase Iii ◽  
Stage Iii ◽  
Recurrence Free Survival ◽  
Meaningful Improvement ◽  
Free Survival ◽  
Stage Iii Melanoma ◽  
The Impact

PURPOSE We conducted the phase III double-blind European Organisation for Research and Treatment of Cancer (EORTC) 1325/KEYNOTE-054 trial to evaluate pembrolizumab versus placebo in patients with resected high-risk stage III melanoma. On the basis of 351 recurrence-free survival (RFS) events at a 1.25-year median follow-up, pembrolizumab prolonged RFS (hazard ratio [HR], 0.57; P < .0001) compared with placebo. This led to the approval of pembrolizumab adjuvant treatment by the European Medicines Agency and US Food and Drug Administration. Here, we report an updated RFS analysis at the 3.05-year median follow-up. PATIENTS AND METHODS A total of 1,019 patients with complete lymph node dissection of American Joint Committee on Cancer Staging Manual (seventh edition; AJCC-7), stage IIIA (at least one lymph node metastasis > 1 mm), IIIB, or IIIC (without in-transit metastasis) cutaneous melanoma were randomly assigned to receive pembrolizumab at a flat dose of 200 mg (n = 514) or placebo (n = 505) every 3 weeks for 1 year or until disease recurrence or unacceptable toxicity. The two coprimary end points were RFS in the overall population and in those with programmed death-ligand 1 (PD-L1)–positive tumors. RESULTS Pembrolizumab (190 RFS events) compared with placebo (283 RFS events) resulted in prolonged RFS in the overall population (3-year RFS rate, 63.7% v 44.1% for pembrolizumab v placebo, respectively; HR, 0.56; 95% CI, 0.47 to 0.68) and in the PD-L1–positive tumor subgroup (HR, 0.57; 99% CI, 0.43 to 0.74). The impact of pembrolizumab on RFS was similar in subgroups, in particular according to AJCC-7 and AJCC-8 staging, and BRAF mutation status (HR, 0.51 [99% CI, 0.36 to 0.73] v 0.66 [99% CI, 0.46 to 0.95] for V600E/K v wild type). CONCLUSION In resected high-risk stage III melanoma, pembrolizumab adjuvant therapy provided a sustained and clinically meaningful improvement in RFS at 3-year median follow-up. This improvement was consistent across subgroups.

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