scholarly journals Surgery for unresectable stage IIIC and IV melanoma in the era of new systemic therapy.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 10032-10032
Author(s):  
Stephanie Blankenstein ◽  
Maureen J.B. Aarts ◽  
Franchette van den Berkmortel ◽  
Marye Boers-Sonderen ◽  
Alfonsus Johannes Maria van den Eertwegh ◽  
...  
Keyword(s):  
Targeted Therapy ◽  
Disease Control ◽  
Systemic Therapy ◽  
Selection Criterion ◽  
Stage Iv ◽  
Stage Iiic ◽  
Term Survival ◽  
Cox Regression Analysis ◽  
Unresectable Stage ◽  
Melanoma Patients

10032 Background: Over the past decade opportunities for surgical treatment in metastatic melanoma patients have re-emerged due to the development of novel systemic therapies. However, selecting patients who will benefit from surgery after systemic therapy is still difficult. The aim of this study is to present data on outcomes of surgery in patients with unresectable stage III and IV melanoma, who have previously been treated with immune checkpoint inhibitors (ICI) or targeted therapy, to provide insight in which patients may benefit from surgery. Methods: Data was extracted from the prospectively collected, nationwide, Dutch Melanoma Treatment Registry (DMTR) onunresectable stage IIIC or advanced/metastatic stage IV melanomapatients who obtained disease control with systemic therapy and underwent subsequent surgery. Disease control was defined as a complete response (CR), partial response (PR) or stable disease (SD). After disease control was achieved with systemic therapy, progressive disease (PD) was allowed as a most recent status of disease prior to surgery, to avoid excluding patients with oligoprogression. Major exclusion criteria were non-cutaneous melanoma and brain metastases. Results: Of 3959 patients in the DMTR database, 154 patients met our inclusion criteria. Of these patients, 79 (51%) were treated with ICI, 61 (40%) with targeted therapy and 9.1% with study or other treatments before surgery. The best response to systemic therapy was a CR in 5.2%, PR in 46.1% and SD in 44.2% of patients. At a median follow-up of 10.0 months (IQR 4-22) after surgery, the median overall survival (OS) had not been reached in our cohort and median progression free survival (PFS) was 9.0 months (95% CI 6.3-11.7). A multivariate cox regression analysis showed that when surgery led to CR or PR, the PFS and OS were better than if surgery led to SD or PD (p < 001). Also, ICI seemed to be more favorable than targeted therapy in both PFS (median of 15 versus 7 months) and OS (median not reached versus 32 months) (p = 0.026 and p = 0.003). Conclusions: We conclude that selected unresectable stage IIIC or stage IV melanoma patients might benefit from surgery after achieving disease control with systemic therapy. Expected residual tumor after surgery could be an important selection criterion. Especially patients undergoing surgery after initial tumor response on ICI have a chance of long-term survival.

scholarly journals Surgery for Unresectable Stage IIIC and IV Melanoma in the Era of New Systemic Therapy

Cancers ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 1176 ◽  
Author(s):  
Stephanie A. Blankenstein ◽  
Maureen J. B. Aarts ◽  
Franchette W. P. J. van den Berkmortel ◽  
Marye J. Boers-Sonderen ◽  
Alfons J. M. van den Eertwegh ◽  
...  
Keyword(s):  
Disease Control ◽  
Systemic Therapy ◽  
Progression Free Survival ◽  
Complete Response ◽  
Stage Iiic ◽  
Free Survival ◽  
Unresectable Stage ◽  
Melanoma Treatment ◽  
Melanoma Patients

Opportunities for surgical treatment in metastatic melanoma patients have re-emerged due to the development of novel systemic therapeutics over the past decade. The aim of this study is to present data on outcomes of surgery in patients with unresectable stage IIIC and IV melanoma, who have previously been treated with immunotherapy or targeted therapy. Data was extracted from the Dutch Melanoma Treatment Registry (DMTR) on 154 patients obtaining disease control to systemic therapy and undergoing subsequent surgery. Disease control was defined as a complete response (CR), which was seen in 3.2% of patients; a partial response (PR), seen in 46.1% of patients; or stable disease (SD), seen in 44.2% of patients. At a median follow-up of 10.0 months (interquartile range 4–22) after surgery, the median overall survival (OS) had not been reached in our cohort and median progression-free survival (PFS) was 9.0 months (95% CI 6.3–11.7). A CR or PR at first follow-up after surgery was associated with both a better OS and PFS compared to stable or progressive disease (p < 0.001). We conclude that selected patients can benefit from surgery after achieving disease control with systemic therapy.

scholarly journals Long-term Survival of Stage IV Melanoma Patients Treated with BOLD Combination Chemotherapy and Intermediate-dose Subcutaneous Interferon-alpha

2018 ◽  
Vol 38 (11) ◽  
pp. 6393-6397 ◽  
Author(s):  
KALLE MATTILA ◽  
PIRITA RAANTA ◽  
VALTTERI LAHTELA ◽  
SEPPO PYRHÖNEN ◽  
ILKKA KOSKIVUO ◽  
...  
Keyword(s):  
Interferon Alpha ◽  
Combination Chemotherapy ◽  
Stage Iv ◽  
Term Survival ◽  
Long Term Survival ◽  
Melanoma Patients ◽  
Stage Iv Melanoma ◽  
Intermediate Dose

Prognostic factors in metastatic melanoma patients treated with biochemotherapy and maintenance immunotherapy

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 9051-9051
Author(s):  
D. R. Minor ◽  
M. Kashani-Sabet ◽  
D. Moore ◽  
C. Kim ◽  
S. S. Venna ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Metastatic Melanoma ◽  
Median Survival ◽  
Performance Status ◽  
Intensive Therapy ◽  
Stage Iv ◽  
Treatment Center ◽  
Term Survival ◽  
Melanoma Patients

9051 Background: Patients with stage IV metastatic melanoma are usually felt to be incurable with a median survival of 6.4 months and a 5-year survival of only 2%. Biochemotherapy has shown promise with long-term survival in selected patients. We felt the study of prognostic factors would determine which patients might benefit the most from this intensive therapy. Methods: 135 consecutive patients with stage IV melanoma treated with decrescendo biochemotherapy followed by maintenance immunotherapy at one melanoma treatment center were studied to determine the most important prognostic factors; these factors were then validated by analysis of 133 patients treated in a multi-center trial at other institutions. Patients were treated using the inpatient regimen of O'Day (JCO23:710s,2005 abstract). Results: Median overall survival (OS) was 16.6 months with 1-year survival of 70% and 5-year survival of 28%. Median progression-free survival (PFS) was 7.6 months with 15% progression-free at 5 years. PFS curves showed no relapses after 30 months, so remissions were durable. For OS performance status 0, normal LDH, stage M1a, and non-visceral sites of metastases were favorable prognostic factors. For PFS performance status 0, normal LDH, female sex, age <50 and stage M1a were favorable prognostic factors Multivariate analysis demonstrated two important prognostic factors for survival: normal serum LDH and the presence of either skin or nodes as one of the sites of metastatic disease. The group with normal LDH and skin or node metastases had a relatively good prognosis with median survival of 44 months and a 5-year survival of 38%. Conversely patients with elevated LDH without any skin or nodal metastases had a poor prognosis, with no long-term survivors. Conclusions: Metastatic melanoma patients treated with biochemotherapy and maintenance immunotherapy that have either a normal LDH or skin or nodes as one of their metastatic sites may have durable remissions of their disease, and this therapy should be studied further in these groups. [Table: see text]

Effect of local therapies on survival in patients with metastatic adrenocortical carcinoma.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e17114-e17114
Author(s):  
Impana Shetty ◽  
David J. Venzon ◽  
Michal Mauda-Havakuk ◽  
Bj Thomas ◽  
Donna Bernstein ◽  
...  
Keyword(s):  
Lymph Node ◽  
Liver Metastases ◽  
Systemic Therapy ◽  
Adrenocortical Carcinoma ◽  
Lung Metastases ◽  
Stage Iv ◽  
Retrospective Chart Review ◽  
Lymph Node Involvement ◽  
Term Survival ◽  
Systemic Therapies

e17114 Background: Adrenocortical carcinoma (ACC) is a rare cancer with an incidence of 0.7 – 2 cases per million persons per year, and generally has a poor prognosis with a 5-year survival rate of 20-25%. In a previous review of 330 patients with ACC, the median overall survival time of patients with Stage IV ACC was 0.9 years. Currently, complete surgical resection is the only curative treatment for ACC. Cases of recurrent or metastatic ACC are infrequently curable by surgery alone and systemic therapies have limited benefit. A previous study has suggested that local interventions to resect liver metastases improve survival. We hypothesize that local therapies increase survival of patients with metastatic ACC and here we describe the characteristics of various types of regional therapies. Methods: We conducted a retrospective chart review of 26 patients with ACC who were seen at the National Institutes of Health (NIH) between 2002 and 2019 and who are currently alive. These patients had multiple interventions that were performed including surgeries, radiofrequency ablations/embolizations/cryoablations and systemic therapies. Results: The group of patients we studied were 92% female and 8% male. The ages ranged from 23 to 77, with an average age of 57. Out of the 26 patients, 11 (42%) patients had liver metastases, 17 (65%) patients had lung metastases, 4 (15%) patients had retroperitoneal recurrence, and 5 (19%) patients had lymph node involvement. All patients with lung, retroperitoneum, liver, and lymph node metastases underwent surgical intervention. In patients with liver metastases, 73% underwent liver-directed therapies and 91% received systemic therapy. In patients with lung metastases, 59% underwent radiofrequency ablation or cryoablation and 94% had systemic therapy. Among the systemic therapies, 15% of patients received zero lines of treatment, 50% of patients received one line, 12% of patients received two lines, 19% of patients received three lines, and 4% of patients received more than three lines of treatment. Conclusions: The analysis of this cohort indicates that multiple local therapies could increase patient survival. ACC metastases are most common in the liver, followed by the lungs. Patients with recurrent/metastatic ACC should be considered for regional therapies such as metastasectomy/ablation in experienced hands which can increase long-term survival in selected patients.

scholarly journals Risk tolerance in adjuvant and metastatic melanoma settings: a patient perspective study using the threshold technique

2021 ◽  
Author(s):  
Carol Mansfield ◽  
Kelley Myers ◽  
Kathleen Klein ◽  
Jeetvan Patel ◽  
Antonio Nakasato ◽  
...  
Keyword(s):  
Stage Iv ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
Risk Tolerance ◽  
Stage Iii ◽  
Acceptable Risk ◽  
Treatment Benefit ◽  
Free Survival ◽  
Unresectable Stage ◽  
Melanoma Patients

Background: Adverse events (e.g., pyrexia) may affect treatment patterns and adherence. This study explored pyrexia risk tolerance among melanoma patients when treatment benefit is unknown versus known. Materials & methods: US respondents with stage III (n = 100) or stage III unresectable/stage IV melanoma (n = 125) chose between hypothetical melanoma treatments, defined by reoccurrence/progression-free survival and pyrexia risk, one resembling standard-of-care and one resembling dabrafenib + trametinib. Respondents chose first when efficacy was unknown and then when efficacy was known; pyrexia risk was varied systematically to define maximum acceptable risk. Results: Maximum acceptable risk of pyrexia was statistically significantly higher when efficacy was known versus unknown in stage III patients (85 vs 34%) and stage III unresectable/stage IV patients (66 vs 57%). Conclusion: Patients accepted higher levels of pyrexia risk when they understood treatment benefit.

Does complete response (CR) with systemic therapy (SRx) translate into long term survival in stage IV melanoma (MM)?

2008 ◽  
Vol 26 (15_suppl) ◽  
pp. 9043-9043
Author(s):  
A. Y. Bedikian ◽  
N. E. Papadopoulos ◽  
K. B. Kim ◽  
W. Hwu ◽  
J. Homsi ◽  
...  
Keyword(s):  
Systemic Therapy ◽  
Stage Iv ◽  
Complete Response ◽  
Term Survival ◽  
Long Term Survival ◽  
Stage Iv Melanoma

Feasibility and clinical impact of next-generation sequencing (NGS) in patients with stage IV or recurrent malignancies.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e14697-e14697
Author(s):  
Fahrettin Covut ◽  
Tariq Zuheir Kewan ◽  
Bicky Thapa ◽  
Abdo S. Haddad ◽  
Timothy Peter Spiro ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Systemic Therapy ◽  
Cox Regression ◽  
Multivariable Analysis ◽  
Cleveland Clinic ◽  
Stage Iv ◽  
Solid Cancer ◽  
Recurrent Cancer ◽  
Cox Regression Analysis ◽  
Best Response

e14697 Background: Feasibility and outcomes of routine NGS in patients with stage IV or recurrent malignancies remain debatable. Methods: We reviewed patients who underwent Foundation One NGS between 9/2012 and 10/2018 after diagnosis of stage IV or recurrent solid cancer at Cleveland Clinic. Overall survival (OS) was estimated by the Kaplan-Meier method. Logistic and Cox regression analysis were performed to identify predictors of receiving targeted gene therapy (TGT) and OS, respectively. Results: We identified 1699 patients, 825 (49%) were female, 1634 (96%) had stage IV and 65 (4%) had recurrent cancer. At diagnosis of stage IV/recurrent cancer, median age was 61 (range: 18 – 94) and ECOG performance score was 0, 1, and ≥ 2 for 578 (34%), 859 (51%), and 258 (15%) patients, respectively. Most common primary cancers were lung (20%), colorectal (17%), urothelial/prostate (12%), and breast (10%). NGS revealed median of 4 mutated genes (range: 0 – 34), ≥ 1 FDA approved TGT was available in 505 (30%) and 1114 (66%) patients for the same and different primary cancer, respectively. Overall, 219 (13%) patients received 247 lines of TGT for median of 3 months (range: 0.1 – 62) based on NGS results. TGT use was via clinical trials for 49 (22%) and off-label for 83 (38%) patients. Best response was complete/partial response for 63 (29%) and stable disease for 40 (18%) patients. Commonly targeted genes were EGFR (12%), ERBB2/3 (11%), BRAF (10%), BRCA1/2 (8%), and PIK3CA (7%). Median follow-up after diagnosis of stage IV/recurrent cancer was 19 months. Two-year OS for TGT and no TGT cohorts were 70% (95% CI: 64 – 77) and 55% (95% CI: 53 – 58), respectively (p < 0.0001). On multivariable analysis, ECOG ( < 2vs ≥2), systemic therapy between diagnosis of stage IV/recurrent cancer and NGS (≥2 vs < 2 lines), and each 1 increase in number of mutated genes were predictors of receiving TGT (p < 0.05 for all). On multivariable analysis, age (≤65 vs > 65), ECOG ( < 2vs ≥2), stage (recurrent vs IV), and systemic therapy before NGS (≥2 vs < 2 lines) predicted longer OS (p < 0.01 for all). Conclusions: In this large cohort, NGS provided further therapeutic options including clinical trials for approximately 1 out of 10 patients with stage IV or recurrent cancer.

scholarly journals Long‐Term Survival of De Novo Stage IV Human Epidermal Growth Receptor 2 (HER2) Positive Breast Cancers Treated with HER2‐Targeted Therapy

2018 ◽  
Vol 24 (3) ◽  
pp. 313-318 ◽  
Author(s):  
Yao Wong ◽  
Akshara Singareeka Raghavendra ◽  
Christos Hatzis ◽  
Javier Perez Irizarry ◽  
Teresita Vega ◽  
...  
Keyword(s):  
Targeted Therapy ◽  
De Novo ◽  
Stage Iv ◽  
Breast Cancers ◽  
Her2 Positive ◽  
Term Survival ◽  
Long Term Survival ◽  
Epidermal Growth

TMB and BRAF mutation status are independent predictive factors in stage IIIC/D/IV melanoma patients receiving adjuvant PD-1 antibodies.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 9524-9524
Author(s):  
Andrea Forschner ◽  
Julia Eckardt ◽  
Peter Martus ◽  
Sorin Armeanu-Ebinger ◽  
Stephan Ossowski ◽  
...  
Keyword(s):  
Predictive Factors ◽  
Braf Mutation ◽  
Antibody Therapy ◽  
Braf V600e ◽  
Stage Iiia ◽  
Stage Iiic ◽  
Mutation Status ◽  
Cox Regression Analysis ◽  
Tumor Stages ◽  
Melanoma Patients

9524 Background: High tumor mutational burden (TMB) is associated with a favorable outcome in metastatic melanoma patients treated with immune checkpoint inhibitors. However, data are limited in the adjuvant setting. As BRAF mutated patients have an alternative with targeted adjuvant therapy, it is important to identify predictive factors for relapse and recurrence-free survival (RFS) in patients receiving adjuvant PD-1 antibodies. Methods: We systematically evaluated all melanoma patients who started adjuvant PD-1 antibody therapy at our center between March 2018 and September 2019 to identify predictive factors for outcome. The median follow-up time from start of adjuvant anti-PD-1 therapy was 22 months. Tumor and normal tissue of all stage IIIC/D/IV patients and of stage IIIA/B patients with relapse were sequenced using a 700 genes panel. Predictive factors for relapse and RFS were identified using univariate and multivariate logistic and Cox regression analysis. RFS was estimated by the Kaplan-Meier method. TMB high was defined as the top 20 % of the cohort, corresponding to TMB values ≥ 20 Var/Mb. Results: A total of 165 patients were included in this study. According to AJCC 8th the initial tumor stages at the beginning of adjuvant anti-PD-1 therapy were as follows: N = 80 stage IIIA/B (48 %), N = 85 stage IIIC/D/IV (52 %). 72/165 patients (44 %) suffered a relapse, 44/72 (61 %) with loco regional and 28/72 (39 %) with distant metastases. Sequencing results were available from 79 / 85 patients with stage IIIC/D/IV. Here we present the results of this cohort. TMB low (OR 17.46, 95%CI 4.03-75.55; p < 0.0001) or absence of BRAF V600E/K mutation (OR 4.13, 95%CI 1.36-12.53; p = 0.012) were statistically significant, independent predictive factors for relapse. Also, with regard to RFS, BRAF mutation status and TMB were statistically significant and independent predictive factors. In the table below we display results for the combined variables. Patients with BRAF V600E/K mutation and TMB high had the best outcome. Conclusions: We identified TMB high as positive predictive marker in stage IIIC/D/IVmelanoma patients with adjuvant PD-1 antibody therapy. In tumors with BRAF V600E/K mutation and concurrent low TMB, adjuvant targeted therapy with BRAF- and MEK-inhibitors may be an alternative. This is also supported by the data on adjuvant dabrafenib and trametinib, which showed a greater advantage in patients with low TMB, presumably due to less tumor heterogeneity.[Table: see text]

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