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Society for Neuro-Oncology meeting shows diverse treatment options emerging for glioblastoma
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The Annual Scientific Meeting and Education Day of the Society for Neuro-Oncology — held in November in Scottsdale, Arizona — featured data from key studies on targeted therapies and immunotherapies.
These data will open the door to new research, and they also offer promise of new therapeutic options for patients with glioblastoma.
Novel data
Roger Stupp, MD, offered perhaps the most notable novel data.
He summarized results of EF-14, a phase 3 trial that evaluated the addition of Optune (Novocure) tumor-treating fields to standard of care with temozolomide. Optune extended median PFS (6.7 months vs. 4 months) and OS (20.8 months vs. 16 months). These results affirmed previously reported interim analysis data.
Martin van den Bent, MD, PhD, presented data from a trial designed to evaluate the antibody–drug conjugate ABT-414 (AbbVie). Patients with recurrent glioblastoma who received two prior therapies received ABT-414, a novel conjugate combining the cell-killing effects of monomethyl auristatin F with an antibody targeting EGFR.
Patients whose tumors featured EGFR amplification demonstrated a 28.3% 6-month PFS rate, as well as a 9-month median survival. Intellance 1, a trial designed to assess the addition of ABT-414 to standard of care for newly diagnosed glioblastoma, is enrolling.
Ingo K. Mellinghoff, MD, presented data on AG-120 (Agios), a first-in-class oral mutant IDH1 inhibitor, in patients with pretreated grade 2 to grade 4 IDH1–mutant gliomas. Nearly all of the nonenhancing expansion cohort exhibited a minor response (9%) or disease stability (83%). Additionally, 64% demonstrated a decreased tumor growth rate per volumetric analysis by imaging. The compound appeared well tolerated.
Immunotherapy
Michael Weller, MD, confirmed the disappointing ACT IV results.
In this phase 3 trial, patients with newly diagnosed EGFRvIII–positive glioblastoma received rindopepimut (Rintega, Celldex Therapeutics). Researchers reported no significant difference in survival between the experimental and control arms (20.1 months vs. 20 months).
Historically, the EGFRvIII mutation has indicated poorer outcomes for patients with glioblastoma, but these results may prompt further research within this population.
Checkpoint inhibitors continue to make news in all tumor subtypes. Multiple ongoing trials studying these agents as monotherapy or combination therapy are accruing.
David Reardon, MD, presented encouraging data from the KEYNOTE-028 trial, which evaluated the checkpoint inhibitor pembrolizumab (Keytruda, Merck) in bevacizumab (Avastin, Genentech)-naive patients with recurrent, PD-L1–positive glioblastoma.
Researchers reported an impressive 12-month OS rate of 74%. One patient achieved partial response, and 12 patients (48%) achieved stable disease. Ten patients (40%) experienced progressive disease. Median time to response (36.3 weeks; range, 7.7-37.6) was longer than what is seen with more traditional therapies.
Frequently reported side effects included fatigue and rash, but therapy appeared well tolerated overall. Additional studies are planned to assess this agent in monotherapy and combination therapy.
Reardon also reported interim results from a trial of another PD-L1 antibody, durvalumab (MEDI4736; AstraZeneca, MedImmune), in bevacizumab-naive patients with recurrent glioblastoma.
Thirty patients received durvalumab monotherapy. Four achieved a partial response and 14 demonstrated stable disease. Median PFS was 3.2 months, and 44% of patients survived 1 year. Fatigue was the most common side effect.
Christine Brown, PhD, presented data from a study that evaluated chimeric antigen receptor–engineered T cells, administered via intraventricular infusions in patients with recurrent glioblastoma that expressed IL13R-alpha-2. The therapy appeared well tolerated, with no dose-limiting toxicities. One patient achieved a complete response that lasted 7.5 months, and five of seven patients who underwent resection showed disease stability for at least 8 weeks.
Low-grade gliomas
van den Bent also presented data from the phase 2 TAVAREC trial in which patients with grade 2 (1p19q intact) and grade 3 gliomas at first recurrence received temozolomide with or without bevacizumab. This was the first controlled trial to evaluate whether bevacizumab would offer a survival advantage in this population. Unfortunately, bevacizumab did not prolong PFS or OS.
Researchers also evaluated the impact of the mTOR inhibitor everolimus (Afinitor, Novartis) in 58 patients with recurrent low-grade gliomas.
Michael Wahl, MD, presented encouraging data that showed 46% of the population completed 12 months of treatment without progression, and the 6-month PFS rate was 84%.
Moving the field forward
Physicians and researchers should be encouraged by these findings, as we continue to move the field forward. Instead of traditional chemotherapy alone, our options are more diverse than ever. Immunotherapy and targeted therapies, as well as novel delivery systems, should continue to grow in popularity. Based on the encouraging data, 2017 should bring opportunities for more clinical trials for recurrent and newly diagnosed glioblastoma.
One cannot help but notice that many of the presented trials involved significant contribution from multiple institutions across various nations. We are hopeful that these joint efforts continue, offering more centers a chance to collaborate and provide the newest and most promising therapies to their patients who have these terrible illnesses.
References:
The following were presented at Annual Scientific Meeting and Education Day of the Society for Neuro-Oncology; Nov. 17-20, 2016; Scottsdale, Arizona:
Brown C, et al. ATIM-13.
Mellinghoff IK, et al. Abstract ACTR-46.
Reardon DA, et al. Abstract ATIM-04.
Reardon DA, et al. Abstract ATIM-35.
Stupp R, et al. Abstract LTBK-01.
van den Bent, MD. Abstract ACTR-07.
van den Bent, MD. Abstract ACTR-09.
Wahl M, et al. Abstract ACTR-32.
Weller M, et al. Abstract ATIM-03.
For more information:
David L. Jennings II, MSN, RN, AGPCNP-BC, is a nurse practitioner at Levine Cancer Institute at Carolinas HealthCare System. He can be reached at david.jennings@carolinashealthcare.org.
Ashley L. Sumrall, MD, is a section chief of neuro-oncology and clinical assistant professor at Levine Cancer Institute at Carolinas HealthCare System. She can be reached at ashley.sumrall@carolinashealthcare.org.
Disclosure: Jennings reports no relevant financial disclosures. Sumrall reports involvement in an investigator-initiated trial using tumor-treating fields. She also reports advisory and speakers bureau roles with Novocure, an advisory role with Amgen, and a speakers bureau role with Bristol-Myers Squibb.