New Study Led by John Theurer Cancer Center Researcher Demonstrates Potential Therapeutic Benefit of TPI-287 with Bevacizumab in Treatment of Aggressive Brain Cancer
June 6, 2016 12:05 PM
A new study co-authored by the John Theurer Cancer Center (JTCC) at Hackensack University Medical Center researchers and presented here at the American Society of Clinical Oncology (ASCO) Hematology (ASCO) annual meeting demonstrates that a combination of TPI-287, a third-generation taxane, combined with the angiogenesis inhibitor bevacizumab (Avastin/Genentech) , improves response rates in patients with glioblastoma multiforme (GBM), a common and often aggressive form of brain cancer.
The study, “Phase 1/2 trial of bevacizumab plus TPI 287, a brain penetrable anti-microtubule agent, in patients with recurrent glioblastoma” (Abstract No. 2055, Poster No. 242), led by Samuel A. Goldlust, M.D., Co-chief, Neurological Oncology Division, Brain & Spine Institute, John Theurer Cancer Center, determined that microtubule inhibitors, a class of drug to which taxanes belong, have demonstrated efficacy in preclinical models of glioblastoma (GBM); however, clinical benefit has been hampered by sub-therapeutic dose delivery. TPI-287 has been shown to overcome this limitation through its ability to cross the blood-brain barrier.
“The results seen in this study are very encouraging and might open a new strategy in recurrent glioblastoma ,” said Andre Goy, M.D., M.S., Chairman and Director, Lymphoma Division, John Theurer Cancer Center. “As oncologists we face a real challenge regarding brain tumors due to lack of penetration of the blood-brain barrier by most anti-cancer agents. We believe that the TPI 287 compound will help us deliver better therapies in this very difficult tumor type. ”
As of January 2016, 24 patients were enrolled in seven TPI 287 dose-escalation cohorts. Among 20 evaluable patients, overall response rate (ORR) was 60 percent -- 12 patients, with three experiencing a complete response, and nine having a partial response. Median and six-month progression-free survival (PFS) were 5.5 months [95 percent C.I. 4.1-6.9] and 37 percent, respectively. Median and one-year overall survival OS were 12.9 months. [95 percent C.I. 10.9-17.9] and 63 percent, respectively, after a 20-month median follow-up.
The study is a multi-center phase 1/2 trial designed to determine the maximum tolerated dose and potential efficacy in patients treated with TPI 287 plus bevacizumab for the treatment of recurrent GBM, with results of the recently completed dose escalation stage to be reported at the ASCO meeting. GBM patients at first or second relapse after standard therapy and without prior exposure to anti-angiogenic agents were eligible for enrollment. Bevacizumab was administered at 10 mg/kg every 2 weeks and TPI-287 every 3 weeks via IV infusion.
No dose-limiting toxicities were reported. Myelosuppression (n = 3) was the only drug-related grade 3/4 adverse event.
Advancement to the phase 2 stage of the trial is underway. Updated safety and efficacy results will be presented at the ASCO meeting.
More information about this trial can be accessed at https://clinicaltrials.gov/show/NCT01933815.
About John Theurer Cancer Center at Hackensack University Medical Center
John Theurer Cancer Center is New Jersey’s largest and most comprehensive cancer center dedicated to the diagnosis, treatment, management, research, screenings, preventive care, as well as survivorship of patients with all types of cancer.
Each year, more people in the New Jersey/New York metropolitan area turn to John Theurer Cancer Center for cancer care than to any other facility in New Jersey. The 14 specialized divisions feature a team of medical, research, nursing and support staff with specialized expertise that translates into more advanced, focused care for all patients. John Theurer Cancer Center provides comprehensive multidisciplinary care, state of the art technology, and access to clinical trials, compassionate care and medical expertise— all under one roof. Physicians at John Theurer Cancer Center are members of Regional Cancer Care Associates, one of the nation’s largest professional hematology/oncology groups. For more information please visit www.jtcancercenter.org.