Home / Health / In a small brain cancer study, immunotherapy produces a prolonged survival

In a small brain cancer study, immunotherapy produces a prolonged survival



SunResearchers reported in a study published Monday that patients with lethal brain tumors, a new and powerful form of cancer treatment before undergoing surgery, helped them live longer on average than patients who started taking the drugs. after surgery.

While the study was small, and while most patients still died at the end of the study period, the researchers said the results suggest that time could be an important factor when it comes to treating glioblastoma, or GBM, with immunotherapies, which are designed to release the immune system. System of cancer cells. Previous attempts to use immunotherapies to help patients with GBM have not achieved broad clinical benefits, and any positive result is striking with a cancer as formidable as GBM, which has an average survival time of only a few years.

"At least we've found a window," said Robert Prins, a tumor immunologist at the Jonsson Comprehensive Cancer Center at UCLA and lead author of the paper. "We had not seen anything before, now I think we're seeing a signal."

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External experts echoed Prins, noting that it was a randomized trial The patients were divided into different treatment groups to compare the results, which gives more weight to the findings. While they cautioned that many of the initially interesting study results are not supported by wider research, they said the study, which was published in the journal Nature Medicine, laid the groundwork for research that would combine different immune boosting strategies at this time. in a patient. disease.

"It's exciting because up until now, the immunotherapies seemed to be on the way to everything else:" Oh, they work on peripheral tumors, but not in the brain, "said Dr. Frederick Lang, president of neurosurgery at the MD Anderson Cancer Center, which was not involved in the research. "This study really instills hope in the field, that these checkpoint inhibitors can be effective if we use them correctly," he added, referring to the type of immunotherapy used in the trial.

The study focused on 32 patients with recurrent GBM: people who already had a first round of treatment (GBM is initially treated with surgery, radiation and a chemotherapy called temozolomide) and whose cancers began to grow again. For the study, half of them started with a checkpoint inhibitor before undergoing surgery to remove as much growth tumor as possible, and the other half waited to start the medication until after the surgery.

Patients in the first group had a mean survival of 417 days, while patients in the second group had a median survival of 228 days. Patients who received the medication before surgery also lasted longer before the tumor started to progress again.

The research was conducted in seven centers from October 2016 to September 2017. In July 2018, when the researchers stopped tracing them for the study, 12 of the patients in the late-onset group had died and nine of the previous-start group had died. died.

By awakening immune cells and knocking down the defenses of cancer cells, immunotherapies have allowed remarkable recoveries for some patients with some cancers. But brain tumors have proven to be one of the most difficult cancers to detect. In December, two research teams reported that they could generate a promising immune response in patients with GBM with another type of immunotherapy called neoantigenic vaccine, but that did not lead to better outcomes for patients.


Brain tumors are particularly difficult to treat for several reasons. It is difficult for medicines in general to penetrate the brain. More specifically, brain tumors do not have as many genetic vulnerabilities for cancer therapies as other tumors. They are also able to control the immunological activity, which turns them into the so-called immunologically cold cancers.

In this study, the researchers tested a checkpoint inhibitor. Control points are one of the ways in which cancer prevents immune cells from destroying tumor cells, so inhibitors work by interfering with these checkpoints. The study used pembrolizumab, which blocks the PD-1 checkpoint and is approved for some forms of cancer such as Keytruda. (Merck, who makes Keytruda, provided the medication for the study).

The researchers initially designed the study only as a scientific survey to compare what happened to the immune system and the tumor in different groups of patients; they did not expect to discover an apparent clinical benefit at the time of the treatments.

"The original idea was to really understand what PD-1 blockage does to the tumor microenvironment, which makes the immune response to the tumor in the brain," said Prins, who is also affiliated with the Parker Institute for cancer immunotherapy.

The researchers are not sure why patients who received pembrolizumab before surgery lived longer, but it is possible that providing the medication and surgery in that order was one or two strokes. Perhaps, according to experts, the drug must be activated by being exposed to proteins on the outside of the tumor cells called antigens, which act as small flags that identify the invaders that the immune system should attack. Then, when the tumor was removed, the curtain of immunosuppression that supports the tumor was dropped, so that the drug could invade the cells left by the surgery.

When the researchers looked at what was going on inside the immune and tumor cells, they found that in the patients who received the medication before surgery, the immune cells were prepared to attack and kill the cancer cells, while their cancer cells were more slow to copy.

But even if these patients lived longer, most of them had still died before the study's end date. Dr. Hideho Okada, director of the brain tumor immunotherapy program at the University of California, San Francisco, compared GBM to a car with a lot of problems: brakes, transmission, the engine, etc. A PD-1 inhibitor such as pembrolizumab is only designed to solve one of these problems, but cancer has many other problems that must be addressed in order for the tumor to be completely eliminated.

"To make the car start working safely again, you have to solve each of these problems," said Okada, who was not involved in the study. "PD-1 is addressing a mechanism, so to take advantage of this preliminary success, we have to plan rational combinations of immunotherapy drugs."

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