2023-07-13 12:21:52
Los papillary craniopharyngiomas (CPP) son a rare type of brain tumor causing considerable morbidity to patients. Although surgery and radiation are often used to treat them, incomplete removal of the tumor and radiation toxicity can leave patients with lifelong health problems after treatment, such as neuroendocrine dysfunction or loss of vision or memory. .
Now, a team of researchers from Mass General Cancer Center (EE.UU.), present the first multicenter treatment protocol for this rare tumor. The study builds on laboratory findings about the genetic factors that drive the growth of PCPs that show that existing cancer drugs can directly interfere with faulty genes in PCPs to stop their progression and dramatically reduce their size.
Building on this breakthrough, the researchers treated 16 patients with a BRAF/MEK inhibitor as part of a phase II clinical trial and found that tumors shrank an average of 91 percent. The results are published in the journal «New England Journal of Medicine».
“All patients who completed one or more cycles of therapy responded to treatment, which is the highest response rate to date for any medical therapy for brain tumors,” says Priscilla Brastianos, director of the Central Nervous System Metastasis Center. “These unprecedented results mark a paradigm shift in the treatment of brain tumors because they demonstrate that, with the right drugs and targets, precision medicine can have a dramatic impact on brain tumors.”
Prior to this study, the laboratories of Brastianos and Sandro Santagata demonstrated that approximately 95 percent of PCPs have a type of mutation in the BRAF gene, known as the BRAF V600E mutation, that drives their cancerous activity.
This type of mutation is also present in some forms of melanoma.
Recently, the Food and Drug Administration of EU (FDA) has approved therapies that inhibit BRAF and a related gene, MEK, to treat melanoma and some other cancers, leading researchers to hypothesize that a BRAF/MEK inhibitor (vemurafenib/cobimetinib) might also be effective in treating PCPs.
These unprecedented results mark a paradigm shift in the treatment of brain tumors.
In this multicenter phase II trial, investigators first screened NPC patients from across the country for BRAF V600E mutations to identify study candidates. Sixteen patients from nine centers enrolled in the study, and 15 completed at least one 28-day course of treatment.
Over the course of four cycles, the mean reduction in tumor size was 91%, with a range of 68% to 99%. Seven patients did not receive any other treatment after stopping vemurafenib/cobimetinib treatment and six have shown no evidence of tumor progression at a median follow-up of almost two years. No patient’s tumor progressed while receiving vemurafenib/cobimetinib, and none have diedo.
Notably, patients experienced adverse drug reactions. Three patients discontinued treatment due to adverse events, with one discontinuing after eight days due to anaphylaxis and acute kidney injury. The most frequent adverse effects were skin rashes, reported by six patients. Even so, many patients tolerated the drugs well and decided to continue therapy beyond the four prescribed cycles as a result of their positive response to it.
Future research could determine the optimal number of vemurafenib/cobimetinib cycles for patients with PCP. The researchers are also advancing other precision medicine clinical trials for patients with meningiomas and brain metastases. Both use precision medicine approaches similar to the one used here to screen patients for biomarkers that indicate their cancers may be treatable with existing therapies.
#study #scenario #brain #tumors