Investigation of BRAF mutation analysis with different technical platforms in metastatic melanoma

2017 ◽  
Vol 213 (5) ◽  
pp. 522-530 ◽  
Author(s):  
Ebru Sener ◽  
Pinar Yildirim ◽  
Ayca Tan ◽  
Ozay Gokoz ◽  
Gaye Guler Tezel
Oncotarget ◽  
2018 ◽  
Vol 9 (63) ◽  
pp. 32232-32237 ◽  
Author(s):  
Delphine Serre ◽  
Julia Salleron ◽  
Marie Husson ◽  
Agnès Leroux ◽  
Pauline Gilson ◽  
...  

2019 ◽  
Vol 11 ◽  
pp. 175883591984887 ◽  
Author(s):  
Lorena Incorvaia ◽  
Giuseppe Badalamenti ◽  
Gaetana Rinaldi ◽  
Juan Lucio Iovanna ◽  
Daniel Olive ◽  
...  

Background: The immune response in melanoma patients is locally affected by presence of tumor-infiltrating lymphocytes (TILs), generally divided into brisk, nonbrisk, and absent. Several studies have shown that a greater presence of TILs, especially brisk, in primary melanoma is associated with a better prognosis and higher survival rate. Patients and Methods: We investigated by enzyme-linked immunosorbent assay (ELISA) the correlation between PD-1 levels in plasma and the presence/absence of TILs in 28 patients with metastatic melanoma. Results: Low plasma PD-1 levels were correlated with brisk TILs in primary melanoma, whereas intermediate values correlated with the nonbrisk TILs, and high PD-1 levels with absent TILs. Although the low number of samples did not allow us to obtain a statistically significant correlation between the plasma PD-1 levels and the patients’ overall survival depending on the absence/presence of TILs, the median survival of patients having brisk type TILs was 5 months higher than that of patients with absent and nonbrisk TILs. Conclusions: This work highlights the ability of measuring the plasma PD-1 levels in order to predict the prognosis of patients with untreated metastatic melanoma without a BRAF mutation at the time of diagnosis.


2019 ◽  
Vol 91 (6) ◽  
pp. 834-841 ◽  
Author(s):  
Xinyang Li ◽  
Enling Li ◽  
Jing Du ◽  
Jiadong Wang ◽  
Bing Zheng

2017 ◽  
Vol 19 (suppl_6) ◽  
pp. vi41-vi41
Author(s):  
Mark van Bussel ◽  
Dick Pluim ◽  
Bojana Milojkovic-Kerklaan ◽  
Daan van den Broek ◽  
Jos Beijnen ◽  
...  

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 8531-8531 ◽  
Author(s):  
Michael S. Gordon ◽  
Harriet M. Kluger ◽  
Geoffrey Shapiro ◽  
Razelle Kurzrock ◽  
Gerald Edelman ◽  
...  

8531 Background: MET and VEGF signaling are implicated in angiogenesis, invasion, and metastasis. Cabozantinib (cabo) is an oral, potent inhibitor of MET and VEGFR2. A RDT evaluated activity and safety in 9 tumor types. Here we report on the metastatic melanoma cohort, including the ocular subtype. Methods: Eligible patients (pts) were required to have progressive measurable disease per RECIST. Pts received cabo at 100 mg qd over a 12 wk Lead-in stage. Tumor response (mRECIST) was assessed q6 wks. Treatment ≥ wk 12 was based on response: pts with PR continued open-label cabo, pts with SD were randomized to cabo vs placebo, and pts with PD discontinued. Primary endpoint in the randomized phase was progression free survival (PFS). Results: Enrollment to this cohort is complete (n = 77); all pts are unblinded. Baseline characteristics: median age 66 years; melanoma subtype: cutaneous/mucosal 70% and ocular 30%; known BRAF mutation 32%; LDH ≥ 1.1 x upper limit normal 35%; bone metastases 19%; median prior lines of therapy 1 (range 0-5). Median follow-up was 2.8 months (range 0.3 - 25). 35 pts (45%) completed the open-label Lead-in stage with 25 pts randomized to continue cabo (n=12) or to placebo (n=13). Median PFS from randomization was 5.7 months for cabo vs. 3 months for placebo (HR=0.3, p =0.055). Median PFS from Study Day 1 was 4.4 months. The estimate of PFS at month 6 (PFS6) is 44%. Evidence of objective tumor regression was observed in 39/65 pts (60%) with ≥ 1 post-baseline tumor assessment including 11/23 pts (48%) with ocular melanoma. Two bone scan evaluable pts demonstrated partial resolution of bone lesions at wk 6 accompanied by pain relief. Most common Grade 3/4 AEs were fatigue (14%), HTN (9%), constipation (4%), and diarrhea (3%); one related Grade 5 AE of diverticular perforation and peritonitis reported during Lead-in stage. Conclusions: Cabo demonstrates activity in metastatic melanoma pts, regardless of subtypes or BRAF mutation status, with improvement in PFS relative to placebo, and high rates of PFS6 and objective tumor regression. The safety profile of cabo was comparable to that of other VEGFR TKIs.


2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 8555-8555 ◽  
Author(s):  
Sophie Brissy ◽  
Caroline Gaudy-Marqueste ◽  
Stéphanie Mallet ◽  
Sandrine Monestier ◽  
Sylvie Hesse ◽  
...  

8555 Background: BRAF mutation in melanoma has been shown to be associated with a trend in favour of a spontaneous worse outcome after metastases in a series of 197 patients in Australia. Objective: To correlate BRAF status in metastatic melanoma with clinicopathologic features and outcome. Methods: In our department in France 182 patients with metastatic melanoma have been tested for BRAF mutation between September 2009 and September 2011. Survival was assessed by log-rank test. Multivariate analysis was performed with Cox model. Results: From 182 patients, 88 (48.3%) were B-RAF mutant; 77 (87.5%) V600E, 4 (4.5%) V600K, and 7 (8%) other mutation subtypes. BRAF-mutant patients were younger than BRAF wild-type patients at diagnosis of primary melanoma (median age 52.3 vs 60.7 years, respectively, p=0.003), and at diagnosis of distant metastasis (median age 53.6 vs 64.1 years respectively, p=0.002). 34 patients were treated by B-RAF inhibitors. There was no significant difference in other demographic features of patients with metastatic melanoma by mutation status. Features of the primary melanoma significantly associated with a BRAF mutation (p<0.05) were histopathologic subtype (SSM), high mitotic rate (≥1/mm2), lower Breslow thickness (median Breslow: 2.2 vs 3.5 mm for BRAF mutant and BRAF-wild-type patients respectively, p=0.016), truncal location and location on occasionally exposed at sun site.The interval from diagnosis of first ever melanoma to first distant metastasis was not significantly different in BRAF-mutant and wild-type patients. The median overall survival (OS) from diagnosis of primary melanoma was 6.5 years for BRAF wild-type patients. Median OS was not reached in BRAF-mutant patients treated (34 of 88) with a BRAF inhibitor, but also in those not treated (p=0.24, and p=0.06 for treated BRAF-mutant vs BRAF wild-type). The overall survival from diagnosis of first distant metastasis was not significantly different (p=0.75). These results remained unchanged in a multivariate analysis. Conclusions: Our results confirm the characteristics of BRAF-mutant metastatic patients, and the efficacy of B-RAF inhibitors, but not that the presence of mutant-BRAF is per se a pejorative predictive marker.


2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 9030-9030 ◽  
Author(s):  
Evan Hersh ◽  
Michele Del Vecchio ◽  
Michael Paul Brown ◽  
Richard Kefford ◽  
Carmen Loquai ◽  
...  

9030 Background: Activating mutations of BRAF V600 can be found in 40%-50% of melanomas and are related to poor prognosis. In a phase 3 trial for the treatment of metastatic melanoma (MM) in chemotherapy-naive patients, nab-paclitaxel (nab-P) vs dacarbazine (DTIC) demonstrated a significant improvement in the primary endpoint of progression-free survival (PFS), assessed by independent radiological review (IRR), and a trend toward prolonged overall survival (OS) at the interim survival analysis. The study also explored the effect of BRAF status on the efficacy parameters. Methods: Chemotherapy-naive patients with stage IV melanoma (M1c stage 65%; elevated LDH 28%) and ECOG performance status 0-1 were randomized to nab-P 150 mg/m2 on days 1, 8, and 15 of a 28-day cycle (n = 264) or DTIC 1000 mg/m2 on day 1 of each 21-day cycle (n = 265) independent of BRAF status. Prespecified subgroup analyses of final PFS and interim OS in subgroups by BRAF status (V600E mutant, wild-type, or unknown) were performed. Results: BRAF mutation status was balanced between the treatment arms, with 36% and 38% of patients with known BRAF mutation status in the nab-P and DTIC arms, respectively. Patient characteristics were also balanced within BRAF subgroups. As shown in the Table, advantage in the nab-P arm vs DTIC arm was observed for both PFS and interim OS regardless of BRAFmutation status. Poststudy BRAF inhibitor treatment was also balanced. Conclusions: In this phase III trial, treatment effect was independent of BRAF mutation status, benefiting all patients who received nab-P vs DTIC. Therefore nab-P should be considered in the armamentarium for all chemotherapy-naive patients with MM. Clinical trial information: NCT00864253. [Table: see text]


2018 ◽  
Vol 36 (15_suppl) ◽  
pp. e21532-e21532
Author(s):  
Mok Oh ◽  
Abdulaali Almutairi ◽  
Nimer Alsaid ◽  
Hani M. Babiker ◽  
Ali McBride ◽  
...  

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