“The use of tumor treating fields (TTFields) as a treatment for patients with brain tumors has, thus far, largely been focused on in glioblastoma, but an upcoming trial aims to expand the use of the device to the grade III patient population, says Daniel O’Connell, MD.
“Currently, the device is only FDA approved for use in grade IV brain tumors, but O’Connell, a neuro-oncologist at UCLA’s David Geffen School of Medicine, anticipates the FDA will grant its approval for use in grade III tumors within the next 2 to 3 months.”
Testing for a biomarker in lung cancer patients’ blood could indicate whether they have brain metastases (cancer spread to the brain). S100B, a protein found in the brain, is usually kept separate from the rest of the body by the so-called blood-brain barrier (BBB). Brain metastases weaken the BBB, allowing S100B to enter the bloodstream. In a recent study, researchers were able to identify 89% of patients with brain metastases by measuring the S100B blood levels of lung cancer patients, although the test also produced a number of false alarms. A blood test for brain metastases would likely be much cheaper than the brain scans currently used.
A new clinical trial will evaluate the safety and effectiveness of NovoTTF therapy to treat non-small cell lung cancer (NSCLC) that has spread to the brain. NovoTTF therapy uses the NovoTTF-100A system, a portable device consisting of an electrical field generator and electrodes that attach to the patient’s scalp. The device produces alternating electrical fields, so-called ‘tumor treating fields’ (TTF), in the brain that are intended to disrupt the process by which tumor cells divide and multiply. NovoTTF therapy is already approved to treat certain kinds of brain cancer that do not respond to other treatments. The new trial will study patients with NSCLC that has spread to the brain and was previously treated with focused, high-powered radiation.
Afatinib (Gilotrif) is a new lung cancer drug for people with non-small cell lung cancer (NSCLC) who have mutations in the EGFR gene. The LUX-Lung 3 clinical trial demonstrated that Gilotrif is superior to chemotherapy as first-line treatment in a global population of patients with EGFR-mutant NSCLC. The LUX-Lung 6 trial confirmed these findings specifically in an Asian population; Asia has a three times higher rate of EGFR-mutant NSCLC than Western countries. More recent evidence indicates that Gilotrif is as effective in patients with rare EGFR mutations as it is in those with common mutations. Finally, Gilotrif recently showed effectiveness in NSCLC patients whose cancer had spread to the brain.
The drug crizotinib (Xalkori) is used to treat non-small cell lung cancer (NSCLC) with mutations in the ALK gene. However, most patients develop resistance to the drug, usually because of further mutations in the ALK gene. A new ALK inhibitor drug, PF-06463922, may offer a solution. PF-06463922 blocked a variety of Xalkori-resistant mutant versions of ALK in cell cultures, and inhibited the growth of Xalkori-resistant ALK-mutant tumors in mice. PF-06463922 also combated tumor cells driven by mutations in ROS1, a gene closely related to ALK, in mouse models. Like Xalkori, PF-06463922 may therefore also be effective for NSCLC patients with ROS1 mutations. Finally, PF-06463922 was able to penetrate into the brain in multiple animal species–important because lung cancer often spreads to the brain.
Lung cancer patients often develop metastases (cancer that has spread) in their bones or brain. A retrospective study of non-small cell lung cancer (NSCLC) patients with metastases revealed that in 39%, the cancer spread affected the bones, and in 30% the spread affected the brain. Bone metastases were more common in elderly patients, were linked to skeletal complications, such as fractures, and were associated with shorter survival (5.5 months vs 9.9 months in patients without bone metastases). Another study found that NSCLC patients who developed new bone metastases were more likely to get brain metastases also. However, patients treated with bevacizumab (Avastin) were less prone to metastases in either the bones (27% vs 43% without Avastin) or the brain (25% vs 33%).
Treatment options are limited for patients with non-small cell lung cancer (NSCLC) that has spread to the brain (brain metastases). Standard chemotherapy drugs often cannot penetrate the brain well enough to treat brain tumors, leaving radiation, surgery, or easing of symptoms as the only choices. However, drugs that target specific mutations in tumors may open up new possibilities. Some NSCLC patients who have mutations in the ALK gene are likely to benefit from treatment with ALK inhibitors like crizotinib (Xalkori). A study of NSCLC patients with ALK mutations in their lung tumors showed that ALK mutations were present in their brain tumors, too. This finding suggests that ALK inhibitors may be effective in treating brain metastases in patients with ALK-mutant NSCLC, as long as the drugs can effectively penetrate the brain.
A phase II study suggests that a MEK inhibitor drug benefits people who have melanomas with NRAS mutations, which currently have no targeted treatments. The drug, called MEK162, shrank tumors in 20% of NRAS-mutated melanoma patients (6 out of 30). MEK162 also shrank tumors in 20% of BRAF-mutated melanoma patients (8 out of 41), as well as tumors that had spread to the brain in two patients. This study is registered with ClinicalTrials.gove as number NCT01320085, and is now recruiting more patients with NRAS mutations.