Radiotherapy and Chemotherapy Combined with Atezolizumab for Newly Diagnosed GBM

Radiotherapy and Chemotherapy Combined with Atezolizumab for Newly Diagnosed GBM.  SNO2020 | Standard regimen of radiotherapy and chemotherapy combined with atezolizumab has preliminary effect on newly diagnosed GBM.

According to a press release “Atezolizumab + Temozolomide and Radiation Shows Promise in Newly Diagnosed GBM” reported by PracticeUpdate on November 25, 2020, the Shiao-Pei Weathers team of the University of Texas MD Anderson Cancer Center, in the 2020 Neuro-Tumor Year (SNO) meeting to announce the preliminary results of its Phase I/II clinical study.

The researchers found that for newly diagnosed glioblastoma, the standard treatment plan of radiotherapy + temozolomide combined with atezolizumab (atezolizumab, PD-1/PD-L1 checkpoint inhibitor) showed a therapeutic effect, which is similar to that of published The clinical trial results are consistent and well tolerated.

Dr. Weathers said in Elsevier’s PracticeUpdate: “Immunotherapy has helped revolutionize the treatment of many cancers. In the field of neuro-oncology, we are trying different types of immunotherapy strategies to treat glioblastoma. I hope we can help Patients provide better treatment results. We are very pleased to have the opportunity to cooperate with Genentech in this clinical trial, and we will jointly explore the role of atezolizumab and other checkpoint inhibitors in the treatment of glioblastoma.

The subjects included in this trial were newly diagnosed glioblastoma patients who were> 18 years old and had only undergone surgery. The patients’ O(6)-methylguanine-DNA methyltransferase (MGMT) status was not screened at the time of inclusion . The primary endpoint of the phase I trial is safety (n = 10), and the phase II trial is the overall survival rate (n = 50).

Secondary endpoints include progression-free survival, overall response rate and duration of response. All 60 enrolled patients were evaluated for efficacy. Related endpoints include tumor immune cell analysis, peripheral blood detection of circulating chemokines/cytokines, and stool analysis of the intestinal microbiome.

The data are as of October 2020, and the median follow-up time is 22 months. At this time, 37 patients have progressed and 30 of them have died. The median overall survival was 19 months (95% CI, 14.2-24.8), and the median progression-free survival was 10.6 months (95% CI, 8.2-16.7).

The median overall survival of patients with MGMT promoter methylation (n = 18) was 29.9 months (95% CI, 11.37-not reached), and the median of patients with MGMT promoter unmethylated (n = 33) The overall survival time was 14.9 months (95% CI, 13.6-24.8).

Thirty-three patients had treatment-related adverse events> Grade 3, of which the most common were elevated liver enzymes (n = 5) and lymphopenia (n = 23).

So far, of the 60 enrolled patients, 20 have undergone a second surgical resection after receiving atezolizumab treatment. Paired tissue analysis before and after treatment will provide valuable insights into the resistance mechanism of anti-PD-L1 drugs. The related content of tumor immunity is still under research.

Dr. Weathers explained that immunotherapy (such as PD-1/PD-L1 inhibition) may have a synergistic effect with radiotherapy, which increases antigen presentation and promotes the inflammatory tumor microenvironment. Most (61%) GBM tumors have ≥1% PD-L1 expression, and 38% of them show at least 5% PD-L1 expression. PD-L1 is also usually expressed on T cells infiltrated by GBM.

Dr. Weathers concluded that, consistent with previous trials of newly diagnosed glioblastoma, this trial proved that atezolizumab combined with the standard treatment of radiotherapy + temozolomide at the same time is tolerable and has a therapeutic effect.

She added: “Although our trial has shown a moderate effect, we hope that the relevant analysis of the tissues before and after atolizumab treatment will help to better understand the mechanism of resistance to anti-PD-L1 therapy. , And provide reference for our follow-up research.”

She continued: “We will analyze the number of tumor immune cells, tumor DNA, mRNA, microRNA, and DNA methylation; perform exome sequencing, RNA sequencing, and microRNA sequencing; evaluate circulating tumor DNA and circulating trends in peripheral blood. Chemical factors/cytokines, and gut microbiome profile in feces. We also plan to analyze the impact of atezolizumab on the GBM immune microenvironment.”

(source:internet, reference only)

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