scholarly journals Melanoma brain metastases: review of histopathological features and immune-molecular aspects

2020 ◽  
Vol 7 (2) ◽  
pp. MMT44
Author(s):  
Lorenzo Salvati ◽  
Mario Mandalà ◽  
Daniela Massi
Keyword(s):  
Brain Metastases ◽  
Local Therapy ◽  
Advanced Melanoma ◽  
Overall Survival Rate ◽  
Histopathological Features ◽  
Dismal Prognosis ◽  
Asymptomatic Patients ◽  
Melanoma Brain Metastases ◽  
Molecular Aspects

Patients with melanoma brain metastases (MBM) have a dismal prognosis, but the unprecedented advances in systemic therapy alone or in combination with local therapy have now extended the 1-year overall survival rate from 20–25% to nearing 80–85%, mainly in asymptomatic patients. The histopathological and molecular characterization of MBM and the understanding of the microenvironment are critical to more effectively manage patients with advanced melanoma and to design biologically driven clinical trials. This review aims to give an overview of the main histopathological features and the immune-molecular aspects of MBM.

Five-year overall survival from the anti-PD1 brain collaboration (ABC Study): Randomized phase 2 study of nivolumab (nivo) or nivo+ipilimumab (ipi) in patients (pts) with melanoma brain metastases (mets).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 9508-9508
Author(s):  
Georgina V. Long ◽  
Victoria Atkinson ◽  
Serigne Lo ◽  
Alexander David Guminski ◽  
Shahneen Kaur Sandhu ◽  
...  
Keyword(s):  
Brain Metastases ◽  
Braf Inhibitor ◽  
Local Therapy ◽  
Leptomeningeal Disease ◽  
Open Label ◽  
Phase 2 Study ◽  
Melanoma Brain Metastases ◽  
Secondary Endpoints ◽  
Local Brain ◽  
Clinical Trial Information

9508 Background: Preliminary data from the ABC (76 pts) and CheckMate 204 (94 pts) trials showed that nivo and nivo+ipi have activity in active melanoma brain metastases, with durable responses in a subset of pts. Here, we report updated 5-yr data from all pts enrolled on the ABC trial (NCT02374242). Methods: This open-label ph2 trial enrolled 3 cohorts of pts with active melanoma brain mets naïve to anti-PD1/PDL1/PDL2/CTLA4 from Nov 2014-Apr 2017. Pts with asymptomatic brain mets with no prior local brain therapy were randomised to cohort A (nivo 1mg/kg + ipi 3mg/kg, Q3Wx4, then nivo 3mg/kg Q2W) or cohort B (nivo 3mg/kg Q2W). Cohort C (nivo 3mg/kg Q2W) had brain mets i) that failed local therapy, ii) with neuro symptoms and/or iii) with leptomeningeal disease. Prior BRAF inhibitor (BRAFi) was allowed. The primary endpoint was best intracranial response (ICR) ≥wk12. Key secondary endpoints were IC PFS, overall PFS, OS, & safety. Results: A total of 76 pts (med f/u 54 mo) were enrolled; median age 59y, 78% male. For cohorts A, B and C: elevated LDH 51%, 58% and 19%; V600BRAF 54%, 56% and 81%; prior BRAFi 23%, 24%, 75%. Efficacy and toxicity are shown in the table. There were no treatment-related deaths. 1/17 deaths in cohort A & 4/16 in cohort B were due to IC progression only. Conclusions: Nivo monotherapy and ipi+nivo are active in melanoma brain mets, with durable responses in the majority of patients who received ipi+nivo upfront. A study of upfront ipi+nivo+/-SRS is underway (NCT03340129). Clinical trial information: NCT02374242. [Table: see text]

Multidisciplinary Approach to Brain Metastasis from Melanoma: The Emerging Role of Systemic Therapies

2013 ◽  
pp. 393-398 ◽  
Author(s):  
Georgina V. Long ◽  
Kim A. Margolin
Keyword(s):  
Brain Metastasis ◽  
Brain Metastases ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Performance Status ◽  
Local Therapy ◽  
Whole Brain Radiotherapy ◽  
Brain Radiotherapy ◽  
First Line Therapy ◽  
Melanoma Brain Metastases

Melanoma brain metastases are common, difficult to treat, and carry a poor prognosis. Until recently, systemic therapy was ineffective. Local therapy (including surgery, stereotactic radiotherapy, and whole brain radiotherapy) was considered the only option for a chance of disease control in the brain, and was highly dependent on the patient's performance status and age, number and size of brain metastases, and the presence of extracranial metastases. Since 2010, three drugs have demonstrated activity in progressing or “active” brain metastases including the anti-CTLA4 antibody ipilimumab (phase II study of 72 patients), and the BRAF inhibitors dabrafenib (phase II study of 172 patients, both previously treated and untreated brain metastases) and vemurafenib (a pilot study of 24 patients with heavily pretreated brain metastases). The challenge and unanswered question for clinicians is how to sequence all the available therapies, both local and systemic, to optimize the patient's quality of life and survival. This is an area of intense clinical research. The treatment of patients with melanoma brain metastases should be discussed by a multidisciplinary team of melanoma experts including a neurosurgeon, medical oncologist, and radiation oncologist. Important clinical features that help determine appropriate first line therapy include single compared with solitary brain metastasis, resectablity, BRAF mutation status of melanoma, rate of progression/performance status, and the presence of extracranial disease.

Clinical outcomes in patients with melanoma brain metastases at a tertiary cancer center.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e13586-e13586
Author(s):  
William J Phillips ◽  
Bryan Lo ◽  
Michael Ong ◽  
Tyler Smith ◽  
Xinni Song
Keyword(s):  
Overall Survival ◽  
Brain Metastases ◽  
Clinical Outcomes ◽  
Checkpoint Inhibitors ◽  
Neurological Symptoms ◽  
Cancer Center ◽  
Significant Prognostic Factor ◽  
Stereotactic Radiation ◽  
Asymptomatic Patients ◽  
Melanoma Brain Metastases

e13586 Background: Brain metastases are observed in more than 40% of all patients with stage IV melanoma. In recent years, more extensive use of stereotactic radiation (STRT) and the advent of immune checkpoint inhibitors and BRAF targeted therapies have positively impacted outcomes in patients with metastatic melanoma (MBM) In this study, we examined real-world clinical outcomes of patients presented with melanoma brain metastases (MBM). Methods: This retrospective review evaluated MBM patients treated at the Ottawa Hospital. Clinical, radiologic, and pathologic variables were collected from the electronic medical records from January 2000 to June 2018. Results: A total of 277 patients fulfilled the inclusion criteria. Median overall survival was 4 months. LDH was the only significant prognostic factor in this study. Over 65% of brain metastases were detected due to the presence of neurological symptoms, while surveillance and restaging identified asymptomatic brain metastases in the remaining patients. Detection by neurological symptoms was related to larger (p < 0.001) and haemorrhagic (p = 0.032) intra-cranial lesions as well as decreased overall survival (HR = 1.2, p = 0.018). With regards to locoregional treatment STRT radiation outperformed WBRT alone in patients with single and oligo (2-6 lesions) brain lesions (HR = 0.149, p = 0.001 for oligo; HR = 0.149, p = 0.003 for single) and was associated with approximately a 3-fold increase in median survival. STRT was used 2-fold less frequently in patients with more than one lesion (54.8% in single; 31.7% in oligo). In patients receiving systemic therapy, immunotherapy is the only modality demonstrated overall survival benefit compared to no systemic treatment (HR = 0.511, p = 0.014). Furthermore, patients receiving STRT in combination with immunotherapy outperformed patients receiving STRT with WBRT (HR = 0.389, p = 0.009). Conclusions: Results from this study support the consideration of routine screening of high-risk asymptomatic patients, the increased use of STRT in patients with multiple intra-cranial lesions. The efficacy of immunotherapy in patients with MBM is consistent with current clinical trial data.

Ipilimumab in patients with melanoma brain metastases, a single-center experience in an expanded access program.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e19027-e19027
Author(s):  
Stephanie Du Four ◽  
Sofie Wilgenhof ◽  
Amelie Clementine Seghers ◽  
Johnny Duerinck ◽  
Bart Neyns
Keyword(s):  
Brain Metastases ◽  
Advanced Melanoma ◽  
Prior History ◽  
Single Center ◽  
Expanded Access ◽  
Single Center Experience ◽  
Expanded Access Program ◽  
Melanoma Brain Metastases ◽  
History Of ◽  
Access Program

e19027 Background: patients (pts) diagnosed with melanoma brain metastases (MBM) have a poor prognosis with conventional treatment options. Ipilimumab (IPI) is a CTLA-4 blocking monoclonal antibody with established activity in patients (pts) with pretreated advanced melanoma. Methods: observational study on the clinical outcome of melanoma pts with a prior diagnosis of MBM among pts treated with IPI (3 mg/kg q3wks x4, allowing for retreatment after a PFS of >24 wks) in an expanded access program at a single center. Results: among the 50 pts who initiated IPI treatment between April 2010 and May 2011, 16 pts had been diagnosed with MBM. Only 1 pt had a solitary MBM, all other pts had > 3 MBM. Baseline characteristics for pts with- and without MBM: M/F 8/8 vs. 20/14; mAge 44- vs. 50y; BRAF V600-mut/wt 10/6 vs 19/15; stage IV-M1c/-a&b 16/0 vs 31/3; WHO-PS 0-1/2 9/7 vs 30/4; LDH >ULN 10/6 vs 23/11; CRP >ULN 10/6 vs 20/14; ALC<1000/mm³ 3/13 vs 11/23. All pts were pretreated with DTIC; 3 pts with stereotactic (stRT), 7 pts with WBRT, and 2 pts with WBRT followed by a stRT boost; 4 pts had no prior therapy for MBM. 7/16 pts with- vs. 24/34 pts without MBM completed IPI-treatment; 3/16 pts with- vs 8/34 pts without MBM had IPI-retreatment. Adverse events were managed following established guidelines and were generally mild/reversible (<20% pts gr3-, none gr4/5) and similar in pts with- or without MBM at the exception of symptomatic radiation necrosis of the brain (RNB) observed in 3 pts (1x gr2, 2x gr3). Following surgery (1pt), and corticotherapy (3pts) all pts recovered their RNB related symptoms. Best objective tumor response (BOR) by RECIST outside the CNS in pts with- vs without MBM was 1PR vs. 1CR/2PR/4SD; according to the immune-related response criteria: 3PR vs. 1CR/2PR/7SD. After a median follow-up of 18 months, 32 pts have died (11/16 with- vs. 21/34 without MBM). The probability for OS was not significantly different for pts with- or without MBM (HR .76 [95%CI 0.36-1.59]; p: .475 by Log-Rank test). Conclusions: in our single-center experience with IPI for pts with advanced melanoma treated in an EAP, the probability for OS for patients with a prior history of MBM was not significantly different from pts without a prior history of MBM.

Development of a New Model of Melanoma Brain Metastases

2012 ◽  
Vol 73 (S 02) ◽  
Author(s):  
M. Amit ◽  
L. Laider-Trejo ◽  
A. Shabtay ◽  
Z. Gil
Keyword(s):  
Brain Metastases ◽  
New Model ◽  
Melanoma Brain Metastases

scholarly journals Melanoma Brain Metastases in the Era of Targeted Therapy and Checkpoint Inhibitor Therapy

Cancers ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1489
Author(s):  
John M. Rieth ◽  
Umang Swami ◽  
Sarah L. Mott ◽  
Mario Zanaty ◽  
Michael D. Henry ◽  
...  
Keyword(s):  
Overall Survival ◽  
Brain Metastases ◽  
Checkpoint Inhibitor ◽  
Checkpoint Inhibitors ◽  
Performance Status ◽  
Multivariable Analysis ◽  
Treatment Strategies ◽  
Poor Performance Status ◽  
Poor Overall Survival ◽  
Melanoma Brain Metastases

Brain metastases commonly develop in melanoma and are associated with poor overall survival of about five to nine months. Fortunately, new therapies, including immune checkpoint inhibitors and BRAF/MEK inhibitors, have been developed. The aim of this study was to identify outcomes of different treatment strategies in patients with melanoma brain metastases in the era of checkpoint inhibitors. Patients with brain metastases secondary to melanoma were identified at a single institution. Univariate and multivariable analyses were performed to identify baseline and treatment factors, which correlated with progression-free and overall survival. A total of 209 patients with melanoma brain metastases were identified. The median overall survival of the cohort was 5.3 months. On multivariable analysis, the presence of non-cranial metastatic disease, poor performance status (ECOG 2–4), whole-brain radiation therapy, and older age at diagnosis of brain metastasis were associated with poorer overall survival. Craniotomy (HR 0.66, 95% CI 0.45–0.97) and treatment with a CTLA-4 checkpoint inhibitor (HR 0.55, 95% CI 0.32–0.94) were the only interventions associated with improved overall survival. Further studies with novel agents are needed to extend lifespan in patients with brain metastases in melanoma.

scholarly journals An open-label, single-arm, phase II trial of buparlisib in patients with melanoma brain metastases not eligible for surgery or radiosurgery—the BUMPER study

2020 ◽  
Vol 2 (1) ◽  
Author(s):  
Teresa Amaral ◽  
Heike Niessner ◽  
Tobias Sinnberg ◽  
Ioannis Thomas ◽  
Andreas Meiwes ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Trial ◽  
Local Therapy ◽  
Progression Free Survival ◽  
Pi3k Inhibitor ◽  
Open Label ◽  
Preclinical Data ◽  
Overall Response ◽  
Intracranial Disease ◽  
Dismal Prognosis

Abstract Background Patients with melanoma brain metastasis (MBM) still carry a dismal prognosis. Preclinical data originated in xenograft models showed that buparlisib therapy was highly effective in therapy-naïve MBM. Patients and Methods In this open-label, phase II trial, we investigate the safety and efficacy of monotherapy with buparlisib, a PI3K inhibitor, in patients with asymptomatic MBM who were not candidates for local therapy. These patients had also progressed under immunotherapy if BRAF wild-type or under targeted therapy with BRAF/MEK inhibitors if carrying a BRAFV600E/K mutation. The primary endpoint was the intracranial disease control rate assessed by the investigators. The secondary endpoints were overall response rate, duration of response (DOR) of intracranial disease, overall response, progression-free survival (PFS), overall survival (OS), safety, and tolerability of buparlisib. Results A total of 20 patients were screened and 17 patients were treated with buparlisib. Twelve patients had progressed under more than 2 systemic therapy lines and 17 had received at least 1 previous local therapy. There were no intracranial responses. Three patients achieved intracranial stable disease; the median DOR was 117 days. The median PFS was 42 days (95% confidence interval [CI]: 23–61 days) and the median OS was 5.0 months (95% CI: 2.24–7.76 months). No new safety signs were observed. Conclusions Buparlisib was well tolerated but no intracranial responses were observed. These results might be explained in part by the inclusion of only heavily pretreated patients. However, preclinical data strongly support the rationale to explore PI3K inhibitor-based combinations in patients with MBM displaying hyperactivation of the PI3K–AKT pathway.

Sign in / Sign up

Export Citation Format

Share Document