Glioblastoma is immunologically "cold" and resistant to single-agent immune-checkpoint inhibitors (ICI). Our previous study of neoadjuvant pembrolizumab in surgically-accessible recurrent glioblastoma identified a molecular signature of response to ICI and suggested that neoadjuvant pembrolizumab may improve survival. To increase the power of this observation, we enrolled an additional 25 patients with a primary endpoint of evaluating the cell cycle gene signature associated with neoadjuvant pembrolizumab and performed bulk-RNA seq on resected tumor tissue (NCT02852655). Neoadjuvant pembrolizumab was associated with suppression of cell cycle/cancer proliferation genes and upregulation of T-cell/interferon-related gene expression. This signature was unique to patients treated with neoadjuvant pembrolizumab and was an independent positive risk factor for survival. Our results demonstrate a clear pharmacodynamic effect of anti-PD1 therapy in glioblastoma and identify pathways that may mediate resistance. However, we did not confirm a survival benefit to neoadjuvant pembrolizumab in recurrent glioblastoma and our secondary endpoint of PFS-6 was 19.5% (95% CI: 9.29-41.2%) for the pooled neoadjuvant cohorts. Our new data suggests some patients may exhibit innate resistance to pre-surgical ICI and require other concomitant therapies to sensitize effectively.
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http://dx.doi.org/10.1038/s41467-024-54326-7 | DOI Listing |
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11685579 | PMC |
Clin Cancer Res
January 2025
University Hospital Essen, Essen, Germany.
Antibodies targeting immune checkpoints, such as PD-1, PD-L1, or CTLA-4, have transformed the treatment of patients with lung cancers. Unprecedented rates of durable responses are achieved in an imperfectly characterized population of patients with metastatic disease. More recently, immune checkpoint inhibitors have been explored in patients with resectable non-small-cell lung cancers.
View Article and Find Full Text PDFNat Commun
December 2024
Center for Neuro-Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Glioblastoma is immunologically "cold" and resistant to single-agent immune-checkpoint inhibitors (ICI). Our previous study of neoadjuvant pembrolizumab in surgically-accessible recurrent glioblastoma identified a molecular signature of response to ICI and suggested that neoadjuvant pembrolizumab may improve survival. To increase the power of this observation, we enrolled an additional 25 patients with a primary endpoint of evaluating the cell cycle gene signature associated with neoadjuvant pembrolizumab and performed bulk-RNA seq on resected tumor tissue (NCT02852655).
View Article and Find Full Text PDFEur Urol
December 2024
Department of Urology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Background And Objective: Bladder cancer (BCa) imposes a substantial economic burden on health care systems and patients. Understanding these financial implications is crucial for effective resource allocation and optimization of treatment cost effectiveness. Here, we aim to systematically review and analyze the financial burden of BCa from the health care and patient perspectives.
View Article and Find Full Text PDFGan To Kagaku Ryoho
December 2024
Breast Center, Kochi Medical School Hospital.
In this study, we report the case of a patient with triple-negative breast cancer who achieved a pathological complete response(pCR)following neoadjuvant chemotherapy but experienced early recurrence and had a poor prognosis. A 46-year-old woman with a diagnosis of triple-negative breast cancer(cT2cN3cM0, cStage ⅢC)received neoadjuvant chemotherapy with dose-dense doxorubicin and cyclophosphamide, followed by weekly paclitaxel. The patient underwent a mastectomy and axillary lymph node dissection, achieving pCR.
View Article and Find Full Text PDFFront Immunol
December 2024
Department of Oncology, Shaanxi Province Tumor Hospital of Xi'an Jiaotong University, Xi'an, China.
Background: The aim of this network meta-analysis was to clarify the efficacy and safety of different immune checkpoint inhibitors (ICIs) in combination with chemotherapy in the neoadjuvant phase for the treatment of locally advanced esophageal cancer.
Methods: We searched PubMed, EMBASE, Web of Science, Cochrane Library, CNKI and WanFang databases from January 2000 until May 2024. The primary endpoints were pathological complete response (pCR), major pathological response (MPR), R0 resection rate, objective response rate (ORR), disease control rate (DCR), treatment-related adverse events(TRAEs) of any grade and TRAEs of grade 3 or higher.
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