Prognosis of metastatic melanoma is changing due to advances in immunotherapy and targeted therapy. However, management of patients with brain metastases in day-to-day practice continues to be a challenge.
We describe a 40-year-old woman diagnosed with symptomatic brain metastases from cutaneous melanoma and Eastern Cooperative Oncology Group 3. She was treated, off label, with
This case is an example of real-life application of advances in targeted therapy.
Tumori 2016; 102(Suppl. 2): e54 - e56
Article Type: CASE REPORT
AuthorsIván Márquez-Rodas, Jose-Antonio Avilés-Izquierdo, Verónica Parra, Ana Álvarez-González, Pedro Borrego, Pilar Fernández-García, Juan-Adan Guzmán-de-Villoria, Yolanda Jerez, Miguel Martin
- • Accepted on 09/07/2015
- • Available online on 27/08/2015
- • Published online on 11/11/2016
This article is available as full text PDF.
The prognosis of metastatic melanoma has been changing since 2010, when breakthrough biological therapies entered the melanoma landscape, as demonstrated by recent phase III clinical trials. However, most clinical trials with these new treatments exclude patients with active brain metastases, despite melanoma being one of the tumors that metastasize to the brain with the highest frequency (1). The same happens to patients with Eastern Cooperative Oncology Group (ECOG) >1. Therefore, outside of specific clinical trials, implementation of the new therapies for this clinical condition is a challenge in day-to-day practice. Melanoma with brain metastases represents an unmet medical need, although melanoma may be the solid tumor with the most paradigm-changing advances in the past 5 years.
We present a case report of a 40-year-old woman with symptomatic brain metastases from a
The patient was diagnosed in April 2009 with cutaneous melanoma in the right arm (stage T3aN2aM0), treated with surgery and adjuvant high-dose α2b interferon for 1 year. In July 2013, the patient presented with left gluteal and thigh pain. An MRI revealed a 42-mm mass in the left sacrum wing, confirmed as metastatic melanoma, with
The patient was referred to our Medical Oncology service in August 2013 to evaluate treatment alternatives. On arrival at our hospital, the patient had an ECOG 0, and no symptoms, but mild pain in the metastatic site, which was controlled with nonopioid analgesics. On physical examination, pathologic lymph nodes in left axilla, right cervical, and submammary subcutaneous metastases were detected. No significant abnormalities (including lactate dehydrogenase [LDH]) were present in the blood analysis.
With the diagnosis of a stage IV (M1c) melanoma, the patient was invited to participate in a clinical trial involving immune-checkpoint inhibitors, reserving the possibility of
During screening, multiple, bilateral brain metastases were detected in the computed tomography (CT) scan, the largest being in the left cingulate cortex (28 × 26 mm) (
Imaging of melanoma brain metastases. (
The patient was admitted and treated, initially, with high-dose steroids and inferior vena cava filter to prevent pulmonary embolism; anticoagulation was withdrawn. An ECOG 3 level due to hemiparesis was recorded at this time.
Since the combination of dabrafenib and trametinib were available for use on compassionate grounds, we decided to treat the patient with this combination. Because of the patient’s symptoms, and since a minimum of 1 week was necessary to solicit approval for this nonlabel treatment, we proceeded with WBRT with standard dose (30 Gy in 10 fractions). The patient began oral dabrafenib (150 mg/12 h) and trametinib (2 mg/24 h) a week after WBRT started. No toxicity was noted. Patient ECOG improved to 2, with an improvement in hemiparesis that allowed her to walk with help. We decided to continue the outpatient treatment, with close monitoring.
The patient continued treatment with dabrafenib and trametinib without relevant toxicity, and continued improving, walking without help, and had almost complete remission of hemiparesis; ECOG was 1 at the first follow-up visit (October 2014). Cervical and axillar lymph node metastases were not palpable in the physical examination.
In January 2014, brain magnetic resonance imaging (MRI) and a body CT scan were performed. The results revealed a major partial response of brain metastases (
A combination of
When brain metastases were diagnosed, neither vemurafenib nor dabrafenib was fully accessible in Spain for patients with melanoma and brain metastases. Since compassionate use was available for the dabrafenib and trametinib combination, we decided to treat the patient with this regimen.
No evidence supported this treatment decision at that time. This combination had not been explored for patients with symptomatic brain metastases without previous treatment, and ECOG >2, since these patients were excluded from these studies and usually from most clinical trials. Recently, a clinical trial was begun to explore the efficacy of dabrafenib and trametinib in previously treated (surgery and/or radiotherapy) and nontreated patients with melanoma and brain metastases, but this was not available at the time (recruitment commenced in February 2014) (5).
With respect to ECOG, phase III clinical trials with vemurafenib, dabrafenib, and its combination excluded patients with ECOG >1 (2, 3, 6, 7). The same applied to phase II clinical trials of vemurafenib (8) and dabrafenib (9) in patients with brain metastases. The ongoing phase II clinical trial for brain metastases excludes patients with ECOG >2 (5). As such, the present case also would have been excluded for this reason even if clinical trials would have been available.
Finally, although WBRT may produce clinical response, and frequently palliates symptoms, it is unlikely to eradicate brain metastases. A median overall survival of 2-4 months has been described for patients receiving radiotherapy alone (10). In our case, we decided to commence with this treatment to offer some treatment while our request for compassionate use of dabrafenib and trametinib was being considered. This treatment option became available 7 days later. The good outcomes we observed could be a synergistic effect of both treatments. Indeed, this synergy is being explored in some clinical trials with
The present case provides insight into management of patients who have an extremely poor prognosis if not treated.
Editorial assistance was provided by Peter R. Turner of Tscimed.com.
- Márquez-Rodas, Iván [PubMed] [Google Scholar] 1, * Corresponding Author (email@example.com)
- Avilés-Izquierdo, Jose-Antonio [PubMed] [Google Scholar] 2
- Parra, Verónica [PubMed] [Google Scholar] 3
- Álvarez-González, Ana [PubMed] [Google Scholar] 4
- Borrego, Pedro [PubMed] [Google Scholar] 5
- Fernández-García, Pilar [PubMed] [Google Scholar] 5
- Guzmán-de-Villoria, Juan-Adan [PubMed] [Google Scholar] 5
- Jerez, Yolanda [PubMed] [Google Scholar] 1
- Martin, Miguel [PubMed] [Google Scholar] 1
The Service of Medical Oncology, Instituto de Investigación Sanitaria Gregorio Marañón, Madrid - Spain
The Service of Dermatology, Instituto de Investigación Sanitaria Gregorio Marañón, Madrid - Spain
The Service of Anatomo-Pathology, Instituto de Investigación Sanitaria Gregorio Marañón, Madrid - Spain
The Service of Oncology-Radiotherapy, Instituto de Investigación Sanitaria Gregorio Marañón, Madrid - Spain
The Service of Radio-diagnostics, Instituto de Investigación Sanitaria Gregorio Marañón, Madrid - Spain