“Patients with glioblastoma multiforme, a type of brain cancer, who recurred following radiation therapy and Temodal (temozolomide), did not survive longer when treated with the PD-1 inhibitor Opdivo (nivolumab) compared to standard-of-care treatment with Avastin (bevacizumab).
The findings mean that the randomized CheckMate -143 Phase 3 trial (NCT02017717) has failed to meet its primary objective.
” ‘[Glioblastoma multiforme] is a historically difficult disease to treat and conventional treatment options have demonstrated limited responses,’ Fouad Namouni, MD, head of Oncology Development and head of Medical at Bristol-Myers Squibb, said in a news release. ‘We remain steadfast in our pursuit of treatments for diseases with the highest unmet need and continue our work to determine how our immuno-oncology agents can potentially improve outcomes for these patients.’ ”
“Cytomegalovirus (CMV)-targeted vaccination plus high-dose chemotherapy with temozolomide can lead to long-term progression-free survival (PFS) and overall survival (OS) in patients with newly diagnosed glioblastoma (GBM), according to a new study published in Clinical Care Research.
“Despite surgical resection, high-dose radiation, and chemotherapy with temozolomide, GBM patients typically survive a median of 15 months. CMV proteins are expressed in more than 90% of GBM. ‘Recent evidence has also demonstrated that CMV-specific T-cell immunity can be generated to recognize and effectively kill autologous GBM tumor cells expressing endogenous levels of the immunodominant pp65 antigen, providing compelling support for the development of CMV-directed immunotherapy for the treatment of GBM,’ stated the researchers, led by Kristen A. Batich, MD, PhD, a researcher in the departments of neurosurgery and pathology at Duke University Medical Center in Durham, North Carolina.”
“A landmark analysis of findings from the EF-14 trial testing the efficacy and safety of tumor treating fields (TTFields) for the treatment of patients with glioblastoma multiforme (GBM) has found that the risk of death was reduced by 37% and overall survival (OS) was extended by a median of 5 months with the use of the device.
“Two-, 3-, 4-, and 5-year overall and progression-free survival (PFS) rates for patients who received TTFields with adjuvant temozolomide were significantly improved over patients who received temozolomide alone, reported Roger Stupp, MD, professor of neurological surgery at Northwestern University Feinberg School of Medicine and associate director for strategic initiatives at the Robert H. Lurie Comprehensive Cancer Center.”
“Treating older patients who have malignant brain cancer with the chemotherapy drug temozolomide plus a short course of radiation therapy extends survival by two months compared to treating with radiation alone, show clinical trial results published in the New England Journal of Medicine.
“For 45% of the study participants, improved survival almost doubled — from 7 months to 13.5 months, says co-principal investigator Normand Laperriere, radiation oncologist at Princess Margaret Cancer Centre, University Health Network. This was linked to a molecular marker that indicated if a DNA repair mechanism against the drug was active. When the mechanism was ‘off,’ tumours responded better to treatment.”
“Adding temozolomide chemotherapy to short-course radiotherapy for older patients with glioblastoma was tied to longer progression-free and overall survival than with a short course of radiotherapy alone, researchers found.
“In a randomized controlled trial of glioblastoma patients ages 65 and up, those on combination therapy had a significantly lower risk of death during the study than those who had only radiation (HR 0.67, 95% CI 0.56-0.80, P<0.001), James Perry, MD, of Sunnybrook Research Institute in Toronto, and colleagues reported in the New England Journal of Medicine.”
With a few exceptions, glioblastoma (GBM) remains largely incurable, and the U.S. Food and Drug Administration (FDA) has approved few treatments for the disease. Surgery (when feasible), radiation, and temozolomide are used in most patients. But even if a newly diagnosed tumor can be surgically excised, recurrences are too common.
In this blog post, I simply list some of the new treatments available in clinical trials for GBM and other high-grade brain tumors. Only drugs that have at least some preliminary results of activity are included, and the list is not meant to be fully comprehensive. The interested reader can judge for herself what might be of interest, keeping in mind that no single treatment is suitable or will work for all GBM patients. Continue reading…
“New research shows that taking molecular variables into account will improve the prognostic classification of the lethal brain cancer called glioblastoma (GBM).
“The study was led by researchers at The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC – James).
“Published in the journal JAMA Oncology, the study found that adding significant molecular biomarkers to the existing GBM classification system improves the prognostic classification of GBM patients who have been treated with radiation and the drug temozolomide.”
“The PD-1 inhibitor nivolumab (Opdivo) was successfully combined with radiotherapy alone or concurrently with temozolomide for patients with newly-diagnosed glioblastoma multiforme (GBM) in cohorts 1c and 1d from the phase I CheckMate-143 study, according to findings presented at the 2016 Society for Neuro-Oncology Annual Meeting.
” ‘The research question was if treatment with nivolumab to block immune checkpoint pathways could potentiate an antitumor immune response and have synergistic effects with radiotherapy or chemoradiotherapy in patients with newly diagnosed GBM,’ stated first author by Antonio Omuro, MD, of the Memorial Sloan Kettering Cancer Center.”
“Treatment with capecitabine and temozolomide (CAPTEM) is an effective therapy for patients with metastatic pancreatic neuroendocrine tumors (pNETs), but the efficacy of several predictive markers previously thought to determine which patients might respond to the regimen could not be validated, according to a presentation at the 2015 NANETS Symposium.
“ ‘In our study we tried to assess the role of potential predictors of response to temozolomide-based regimens in metastatic pNETs,’ according to lead author Mauro Cives, MD, who presented the findings at the 2015 North American Neuroendocrine Tumor Society symposium. The markers the investigators evaluated were expression of MGMT, proliferative activity, and ALT activation.
“Investigators looked at 143 patients with metastatic pNETs treated at Moffitt who had undergone therapy with CAPTEM and retrospectively evaluated them for radiographic response. ‘This is the largest reported cohort of pNET patients treated with temozolomide-based chemotherapy,’ said Cives, a research associate in the Department of GI Oncology at the Moffitt Cancer Center and Research Institute in Tampa, Florida.”