From May 29 – June 2, National Brain Tumor Society Research and Scientific Operations staff attended the 2015 American Society of Clinical Oncology (ASCO) Annual Meeting, one of the most important cancer research meetings of the year. Each year, we attend ASCO to learn about the latest research on emerging new treatments and get updates on some of the most promising clinical trials taking place in the brain tumor research space.
Earlier, we provided a link to check out a great round-up post from our Associate Director of Scientific Operations, Dr. Jennifer Helfer, on brain tumor news that broke at ASCO. Today we take a bit deeper dive into the top news from the conference, and what its implications are for the brain tumor community. Since last year’s ASCO recap ended up being our sixth most popular read of 2014, we’ll follow the same format:
ReACT Results Excite
Dr. David Reardon of the Dana-Farber Cancer Institute presented on study called ReACT – a randomized, double-blind Phase II study of a vaccine being developed by Celldex Therapeutics called Rintega (rindopepimut) in patients with EGFRvIII-positive, recurrent glioblastoma (GBM).
Previously, Rintega – which uniquely targets EGFRvIII, a commonly mutated form of a gene called EGFR that is considered to be a key “driver” mutation in GBM – has shown encouraging clinical benefit (effectiveness and safety) in three Phase II studies in newly diagnosed GBM patients expressing the mutation. Information from compassionate use had also suggested that rindopepimut may also provide benefit in relapsed GBM. As Dr. Reardon noted, this has been especially heartening as relapsed GBM patients with the EGFRvIII (about 30% of GBM patients) are notoriously difficult to treat.
The results presented at ASCO 2015 showed that Rintega produced favorable and positive effects, extending overall survival by a median of around two months with a statistically significant survival benefit -over the course of the entire study- in vaccine treated individuals compared to non-vaccine treated patients. The treatment also reduced the need for steroids. The magnitude of this reported benefit was considered comparable to the effects of an immunotherapy called Ipilimumab, which justified its approval for melanoma in 2010. The next step is for Celldex to move forward with a Phase III trial in recurrent GBM or possibly seek an “accelerated approval” from the FDA.
Read the press release from Celldex here.
An update from Celldex’s Phase III ACTIV study with Rintega in newly diagnosed GBM patients is due in the summer of 2015.
Update on Novocure’s Optune (Tumor-Treating Field)
Much of the buzz coming out of the Society for Neuro-Oncology Annual Meeting last November was surrounding interim results from a study on the device developed by Novocure called Optune (formerly Novo-TTF-100A system). Those results reported that Optune, used in combination with temozolomide (also know as Temodar or TMZ), demonstrated improved survival benefit in newly diagnosed GBM patients, compared to treatment with temozolomide alone. Patients who received both Optune and temozolomide, on average, survived 19.6 months, compared with an average survival of 16.6 months for those who only received temozolomide. Additionally, the trial showed patients using Optune had an increase in “progression free survival” of three months over patients who didn’t receive Optune (7.1 months vs. 4.0 months). Finally, the percentage of patients surviving at least two years was greater in the Optune and temozolomide arm (43%) than in the temozolomide alone arm (29%). No major added toxicities or adverse effects to patients were observed in the Optune/temozolomide arm.
The data from this interim analysis were significant enough for an independent review committee to recommend that Novocure can end their trial early, so the patient in the control arm of the clinical trial could “cross-over” and receive Optune treatment.
At ASCO 2015, Novocure presented the full, final results from this study. The data for the full analysis were reported to be comparable to those for the interim dataset. There was a statistically significant increase in the median for progression-free survival of 2.9 months, as well as for overall survival of 2.8 months in the Optune treated patients compared to the temozolomide-only group. This again translated into 2-year survival rates of 43% vs. 29%, respectively. No significant added toxicity, beyond the effects of standard chemo- and radiotherapy, was seen in the Optune treated patients. Quality of life and cognitive function were comparable across the two groups. Read the full press release here.
The U.S. Food and Drug Administration (FDA) is currently reviewing the available data on the use of Optune as a treatment for newly diagnosed GBM patients. (Note: Optune is already approved for recurrent GBM patients).
National Brain Tumor Society encourages GBM patients to talk with their medical team about Optune, so as to consider all of the potential treatment options available.
Immunotherapy Trial News
Continuing the recent trend, immunotherapy once again was a leading topic of discussions and presentations at ASCO. Below is a round-up of some of the immunotherapy trials that were reported on this year in GBM. Note all of these trials are still very earlier the evaluation process:
- Phase II multicenter study of gene mediated cytotoxic immunotherapy as adjuvant to surgical resection for newly diagnosed malignant glioma: (http://meetinglibrary.asco.org/content/152063-156) David S. Baskin et al.
- Newly diagnosed glioblastoma patients treated with an autologous heat shock protein peptide vaccine: PD-L1 expression and response to therapy: (http://meetinglibrary.asco.org/content/153509-156) Orin Bloch et al
- Phase I study of ABT-414 mono- or combination therapy with temozolomide (TMZ) in recurrent glioblastoma (GBM): (http://meetinglibrary.asco.org/content/149604-156) Hui K. Gan et al
- Oncolytic polio/rhinovirus recombinant (PVSRIPO) against recurrent glioblastoma (GBM): Optimal dose determination: (http://meetinglibrary.asco.org/content/152561-156 ) Annick Desjardins et al
- Comparative impact of treatment on clinical benefit in patients with glioblastoma (GBM) enrolled in the phase II trial of ICT-107: (http://meetinglibrary.asco.org/content/148054-156) Terri S. Armstrong et al.
News for Other Primary Brain Tumor Types:
While GBM is often a major focus of neuro-oncology research and drug development, because it is the most aggressive and difficult to treat of primary brain tumors in adults (and thus many learnings from GBM could subsequently be applied to other, less aggressive tumor types), there were a number of presentations on trials for other brain tumor types for both adults and pediatric patients:
- Phase 1 study of dabrafenib in pediatric patients with relapsed or refractoryBRAF V600E high- and low-grade gliomas (HGG, LGG), Langerhans cell histiocytosis (LCH), and other solid tumors (OST): (http://meetinglibrary.asco.org/content/149751-156) Mark Kieran et al
- Outcome of neurofibromatosis type 1 patients treated with first line vinblastine for optic pathway gliomas: A Canadian multicenter study: (http://meetinglibrary.asco.org/content/152904-156) Alvaro Lassaletta et al
- A phase II study of temozolomide in the treatment of adult patients with supratentorial low-grade glioma: (http://meetinglibrary.asco.org/content/142883-156) Michael Traut
- Phase II trial of bevacizumab in patients with surgery and radiation refractory progressive meningioma: (http://meetinglibrary.asco.org/content/150018-156) Sean Aaron Grimm et al.
- Long-term analysis of the NOA-04 randomized phase III trial of sequential radiochemotherapy of anaplastic glioma with PCV or temozolomide: (http://meetinglibrary.asco.org/content/110020?media=vm) Wolfgang Wick et al
- Long-term survival in patients with primary CNS lymphoma: Results from the G-PCNSL-SG1 trial. (http://meetinglibrary.asco.org/content/147730-156) Patrick Roth et al
To access more information and news from ASCO 2015 acess news and abstracts from the CNS track, here
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