Glioma is one of the most common brain tumors, and it is also one of the most deadly cancers, and its notoriety is no less than the "cancer king" pancreatic cancer. The average survival time is only 1 year, and the five-year survival rate of is less than 5%. There is currently no cure for this tumor!
Brain glioma is difficult to treat. One reason is that it hides in the brain, protected by the blood-brain barrier, and many drugs cannot enter it. Of course, there is another reason. There is no suitable animal model that can be used to test which drugs are effective in treating glioma.
In 1976, the US Food and Drug Administration (FDA) approved lomustine as a therapeutic drug for intracranial tumor . In the following 40 years, only three drugs for the treatment of brain cancer were officially approved:
In 1996, carmustine chips were approved for recurrent glioma. At present, Carmustine is also approved as an adjuvant treatment for newly diagnosed patients with glioma who have undergone surgery.
In 1999, temozolomide (TMZ) was approved for use in patients with grade 3 anaplastic astrocytoma. At present, the indications of this drug have been extended to newly diagnosed gliomas as maintenance treatment after radiotherapy.
In 2009, bevacizumab received accelerated approval,It is used for patients with glioma whose condition has deteriorated after treatment.
After ten years of sharpening a sword, it should be possible to grind a good sword!
But it takes ten years to come up with a drug,
glioma is very limited.
Ten years later, this bottleneck was finally broken!
Ten years of great changes! The world's top ten treatment advances for glioma!
In the past ten years, the treatment of glioma has been targeted therapy, immunotherapy (1. Immune checkpoint inhibitors; 2. Adoptive cellular immunotherapy; 3. Therapeutic vaccines; 4. oncolytic virus has made unprecedented progress, and is giving patients new hope of survival (see the table below). The Medical Department of Global Oncologist Network has counted the recent targeting of glioma , and the progress of immune blockbuster treatment is for your reference. If you want to know or apply for the following treatment options, you can call the Medical Department of Global Oncologist Network for preliminary evaluation.
Targeted therapy
1 in the past thirty years,Newly diagnosed glioblastoma patients do not have any new drug treatments, temozolomide is the only option. In recent years, the targeted therapy of brain tumors has made major breakthroughs, including NTRK.
01
82% tumor shrinkage! The revolutionary anticancer drug Larotrectinib has captured the fortress of deadly brain tumors
Since 2018, the world's first targeted drug with no restriction on cancer species-larotinib, has become another "diamond" target since its launch The dot gene-NTRK quickly spread to the circle of cancer friends.
announced the latest clinical data at the ASCO conference in 2021, which is very exciting! The enrolled patients with central nervous system tumors, whether adults or children, had a rapid and long-lasting response after receiving Larotrectinib: Of the 28 evaluable patients, 23, which is 82% of patients The lesions have shrunk , for patients with brain tumors who have no medicine for a long time, so regardless of age, larotinib brings new hope of survival! Original link: 82% of patients' tumors shrank! The revolutionary anti-cancer drug Larotrectinib has taken the deadly brain tumor fortress
A 3-year-old girl,She was diagnosed with high-grade glioma when she was 5 months old. After undergoing surgery, radiotherapy and chemotherapy, her condition continued to deteriorate. Clinicians said that there was no better treatment. But her parents refused to give up, and used her surgical tissue slices to do whole-genome sequencing . The results showed that there was an ETV6-NTRK3 fusion. Fortunately, she was included in the clinical trial of larotrectinib. Only 4 weeks later, her sleepiness, headache or vomiting improved significantly, she was eating well, and she spoke clearly. After 6 weeks, she was able to walk independently, communicate normally, and was energetic. By the eighth week, she ran, danced and continued to study. The following CT examination confirmed that the lesions in her brain were almost in complete remission!
Red arrow: brain tumor subsided after 2 months of treatment and continued to regress after 5 months; strong1 span1 _span452 strong span1 _span452 Significant improvement at month, and almost complete remission at 5 months;
Red circle: intraventricular lesions improved after 2 months, and completely resolved after 5 months.
It is worth mentioning that according to statistics, the frequency of NTRK fusion in brain tumors differs greatly between children and adults, between 3~40%, _span _strongThe most common glioblastoma multiforme is the NTRK2 fusion. Therefore, patients with tumors are tested for NTRK fusion, especially in the absence of known driving factors, especially in infants with glioma.
In addition to larotinib, targeted drugs marketed for NTRK fusion and Entrectinib _strong4span Entrectinib _strongin strong 49 strong 49strong Entrectinib _strongin -195/BAY-2731954; NCT03206931, NCT03215511) and Repotrectinib (TPX-0005; NCT04094610, NCT03093116) . Almost every one is a "curable" special drug. Therefore, it is recommended that brain tumor patients undergo genetic testing to see if there is any These mutations. If you have done a genetic test, you can call the Medical Department of the Global Oncologist Network for interpretation and assess whether you can be included in the relevant drug trials.
Original link: finally here! The so-called “curing line” anti-cancer drug larotinib has officially launched clinical trials in China!
Entrectinib, an American anticancer drug, has finally been officially recruited in China! 100+ patients are expected to join the group!
45 types of tumors have "diamond" target NTRK! 13 new drugs worldwide usher in a new era of broad-spectrum anti-cancer!
02
PTGR1: The tumor shrinks by more than 85%! FDA granted LP-184 orphan drug designation for malignant glioma
August 31, 2021 LP-184 obtained the FDA orphan drug designation for glioblastoma and other malignant gliomas. This is the second orphan drug qualification that LP-184 has obtained. In August 2021, the FDA has just granted LP-184 orphan drug qualification for pancreatic cancer. Original link: Express | LP-184 obtained FDA orphan drug designation for glioblastoma and other malignant gliomas
LP-184 is a DNA repair pathway, namely nucleotide excision Repair (NER) and homologous recombination (HR) pathway drugs. Previous analysis has proven that patients with glioblastoma multiforme, PTGR1, and defective DNA damage repair components can benefit potentially from LP-184.
In a preclinical study conducted in collaboration with Johns Hopkins University, it was found that LP-184 resulted in more than 2 subcutaneous xenograft models of glioblastoma multiforme: U87 and M1123 106% tumor growth inhibition. 3Compared with mice that did not receive any drug treatment, the drug was also found to prolong the survival of mice with the disease's intracranial implanted tumor model (U87).
When LP-184 was administered intravenously within 2 cycles, the drug reduced the volume of subcutaneous xenograft tumors in mice by more than 85%.
This drug is currently in the preparatory phase of human clinical trials.We look forward to more amazing clinical data.
03
PI3K: The new drug Paxalisib enters the first-line treatment! It is expected to replace mozolomide
In the near future, paxalisib (code-named GDC-0084) for the treatment of glioblastoma multiforme (GBM) Phase II data was published (NCT03522).
paxalisib is a small molecule inhibitor of PI3K/AKT/mTOR pathway that can cross the blood-brain barrier. It is currently being developed to treat the most common and aggressive primary brain Cancer-glioblastoma.
Patrick Y. Wen, MD, professor of neurology at Harvard Medical School and Dana-Farber Cancer Institute, said that a new treatment for glioblastoma is imminent. GDC-0084 has the potential to become an important new drug for the treatment of this extremely challenging disease.
PATRICK
director
PATRICK Y. WEN Dannafabo Cancer Institute
neuro-oncology center
is good at specialties: brain tumor, spinal cord tumor, meningioma, cancer-related syndrome, glioma, meningioma.
immunotherapy is called "span4span
span4span strong 11 strong 49 strong tumor" Containing very few immune cells, there is a system called the blood-brain barrier in the brain, which prevents T cells from entering the brain tissue. It is very difficult for these immune cells to produce an immune response against tumors. Therefore, "anti-cancer drug" PD-1 is also helpless with it. Scientists have been looking for effective immunotherapy methods to break this bottleneck.
04
Brain tumor vaccine: double the survival time! SurvaxM, a new brain tumor vaccine, was born
SurVaxM, also known as SVN53-67 / M57-KLH peptide vaccine,It is an immunotherapy, which has been proved to be safe and tolerable in patients with malignant glioma in a phase I study.
The latest results of an ongoing phase II clinical study show that the SurVaxM vaccine is safe even in the most difficult to treat patients. Susceptibility, and can prolong the survival period. The median overall survival time of patients receiving SurVaxM was 30.5 months, while patients receiving standard care were 14.8 _span4 _strong 52 months. More than doubled.
This is a synthetic vaccine made of natural amino acids and will be broken down during an immune response, so the side effects are minimal.
Based on the positive results of the initial phase I and phase II studies, the research team hopes to conduct large multicenter randomized phase II clinical trials in both China and the United States. Once this vaccine starts to recruit, we will release information as soon as possible.
05
Brain tumor vaccine: dendritic cell vaccine -GBM1 is here!
At the ASCO conference in June 2021,The Phase II clinical trial data of the new dendritic cell vaccine AV-GBM-1 was announced. Research shows that this new vaccine can significantly improve the progression-free survival rate of newly diagnosed glioblastoma patients, which is higher than standard treatment options.
In this study, 57 patients received 8 doses of the vaccine within 6 months. The result of showed: _strong52 span1 of _strong 52 span _span4
span1 span _span4 The progression-free survival (PFS) is 10.4 months, and the standard treatment plan (radiotherapy combined with temozolomide) in the control group is only 6.9 months, which is a milestone!
In addition, the AV-GBM-1 vaccine is generally well tolerated. Researchers look forward to demonstrating more benefits in a randomized phase 3 multicenter trial.
AV-GBM-1 is a patient's own specific dendritic cell vaccine, which aims to use the patient's own immune system to find and eliminate cancer cells. This dendritic cell vaccine It can carry the specific antigen information extracted from the tumor tissue after the operation. After the injection, the antigen information is transmitted to the T cells to stimulate the tumor-killing activity.
Although the autologous vaccine for patients is logically complicated,However, it is a feasible method that can be performed simultaneously with temozolomide and radiotherapy; it can also be injected with AV-GBM-1 vaccine after recovery from chemotherapy and radiotherapy. Click here for details: Dendritic cell-based cancer immunotherapy handbook (2021 patient version)
06 _strongspan strong span1 Vaccine: strong span1 strong 49strong 06 _strongspan strong ppanax vaccination _strongspan1 span1 strong 49strong _strongspan1 L is expected to be launched
The DCVax®-L vaccine of Northwest Biotherapeutics, a biotechnology company, is believed to be familiar to most brain tumor patients.
Interim data from the previously announced phase III clinical study. Among the patients enrolled in the clinic for more than three years, 67 cases (30%) survived more than 30 months, and 44 cases (24.2%) survived more than 36 months. The median survival span of of these patients is estimated to be 46.5 to 88.2 months. At the time of analysis, 108 (32.6%) of the 331 patients who participated in the trial were still alive.
So far, the clinical trial of DCVax-L has been conducted for 12 years, which is extraordinary. The first patient was enrolled 12 years ago, and the last patient was enrolled 5 years ago .Everyone is looking forward to the final data of this therapy. We have found relevant information. It is expected that the final phase 3 trial results should be released in late June or early July. The detailed data will be announced at the relevant oncology conference in the near future. We look forward to this. With the positive data of this therapy, we also look forward to its approval as the first immunotherapy for brain tumors as soon as possible!
07
Oncolytic virus: 1-year survival rate of 92.3% vs 15%! The world’s first oncolytic virus, teserpaturev, was approved for marketing in Japan
June 11, 2021, Daiichi Sankyo announced that the oncolytic virus therapy Delytact (teserpaturev/code G47∆, (Hereinafter collectively referred to as teserpaturev) has been approved by by the Ministry of Health, Labour and Welfare of Japan and officially launched for the treatment of malignant glioma! Original link: approved! The world's first oncolytic virus therapy for the treatment of brain tumors is launched in Japan! These ten points must be known
It is worth mentioning that this is the world’s first oncolytic virus therapy approved for the treatment of primary brain tumors, and is another worthy engraving in the history of tumor treatment. Milestone! The approval of
teserpaturev is based on the excellent data of a single-arm phase 2 clinical trial conducted by Dr. Tomoki Todo at the University of Tokyo in patients with recurrent glioblastoma.The results of showed that: oncolytic virus treatment group had a 1-year survival rate of 92.3% (12 out of 13 cases of survived more than 1 year after treatment compared to standard span), Compared with treatment of 1-year survival period 15% , it greatly improves the survival rate of patients with glioma.
The third-generation oncolytic virus Teserpaturev introduces additional deletion mutations to enhance the anti-tumor effect. The new oncolytic virus has been proved to have stronger replication ability and higher anti-tumor activity. Studies have found that the therapy is effective in glioma, breast cancer, prostate cancer, schwannoma, nasopharyngeal carcinoma, and hepatocellular carcinoma. It is effective in cancer, colorectal cancer, malignant peripheral nerve sheath tumor and thyroid cancer. In addition, it has also been found that the therapy can effectively eliminate cancer stem cells derived from human glioblastoma and has the potential to prevent recurrence.
08
Oncolytic virus: complete relief! FDA granted PVSRIPO breakthrough therapy designationThe blockbuster study that significantly prolonged the lives of patients with glioblastoma was published in the top medical journal " New England Journal of Medicine " (NEJM). The study has attracted widespread attention in the medical community. As of March 20, 2018, 8 patients had responded to the treatment, and the glioma lesions of 2 patients had completely disappeared, achieving complete remission!
Currently, PVSRIPO is conducting phase II clinical trials at several well-known cancer centers in the United States, including Massachusetts General Hospital , Dana-Farber Cancer Institute, etc., and is still recruiting. In 2016, the FDA awarded this oncolytic virus therapy breakthrough treatment designation.
09
strong49 The tumor disappeared completely! Domestic clinical trials are carried out
In December 2016, NEJM reported a case of using CAR-T technology to treat glioma. A 50-year-old man was diagnosed with high-grade glioma and underwent conventional treatments such as surgery, radiotherapy, and temozolomide chemotherapy. The disease relapsed 6 months later. At this time, he participated in a clinical trial and received CAR-T treatment targeting IL13Rα2. However, this therapy is somewhat "horrifying."
The doctor in charge found through an MRI examination: This patient has 5 lesions in the brain; therefore,First of all, three of the large ones are cut off by surgery, and the remaining two smaller ones cannot be removed due to their deep location. The doctor in charge inserted a tube directly into his lesion, and then injected CAR-T cells through this tube, divided into 3 batches, and carried out multiple cell infusions. In the end, the tumor disappeared completely and the curative effect was maintained for about 8 months.
At present, the prospective study of CAR-T therapy for brain tumors is also actively conducting clinical trials in China.
brain tumors Black &
10
field therapy: five-year survival rate of turn 6 times ! The most sci-fi anti-cancer black technology in history
Electric field therapy is a completely new treatment plan that is completely different from surgery, radiotherapy, and drug therapy. This anti-cancer black technology for cancer cells with rapid mitosis was once hailed as the fourth new method of tumor treatment by an article published by the internationally renowned cancer journal Clinical Cancer Research.It has received much attention since its inception!
Electric field therapy is known as a milestone in the treatment of brain tumors! This is the first time in more than ten years that there has been an ineffective treatment that can significantly improve the survival of patients with brain blastoblastoma! The reason why electric field therapy is effective for glioma is that it is a type of tumor cell that divides abnormally rapidly. The electric field treatment sets up a sufficiently low intensity and low frequency electric field, which only affects cancer cells that are rapidly mitotic, and eventually causes cancer cell membranes to bubble, rupture, and die~
According to the latest published clinical data, During the 5-year follow-up, regardless of health status, age, gender, and tumor size, the electric field therapy plus chemotherapy group lived longer. The five-year survival rate is as high as 13%, compared with only 5% in the chemotherapy group. Extends more than twice! This is absolutely unprecedented.
Since the tumor electric field treatment combined with temozolomide, 1 out of 7 patients with has a survival time of more than 5 years. In addition, the effect of tumor electric field therapy is closely related to compliance, When patients wear more than 22 hours a day, the five-year survival rate can be increased to 29.3%, which is almost 6 times the five-year overall survival rate of temozolomide alone. ! Brings an unprecedented breakthrough in survival for patients with brain tumors! Moreover, this treatment has almost no side effects caused by radiotherapy and chemotherapy. The most common one is the rash on the contact area of the electrode pad .
Electric field therapy is known as a milestone in the treatment of brain tumors! This is the first time in more than ten years that there has been an ineffective treatment that can significantly improve the survival of patients with brain blastoblastoma! electric field therapy is the biggest breakthrough in the treatment of glioblastoma in at least ten years.
Further reading:
official announcement! The American electric field therapy was awarded the qualification of innovative medical device by China Food and Drug Administration! Coming soon
electric field therapy is the first to announce clinical data for Asian cancer patients! Coming to China!
Complete three levels and cut six cancers! American anti-cancer black technology-Optune will be launched in China soon!
Hong Kong, China's first terminal cancer patient using electric field therapy has returned to normal life!
The future is here! Brain tumor patients usher in hope of long-term survival!
Although glioblastoma is the most common malignant tumor, the 5-year relative survival rate is only 6.8%, but it is believed that more and more new treatment technologies and new drugs will emerge in the near future. Treatment of glioblastoma, and the various new research mentioned in this article will not stop here, such as electric field therapy, boron neutron capture therapy (BNCT), photoimmunotherapy and other new technologies have come out one after another, we Will be introduced in detail in the next article. We are looking forward to more and more unexpected clinical research results in the future.
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