The Society for Neuro-Oncology (SNO) Annual Scientific Meeting is a multi-day conference that serves as one of the most important gatherings in the field of brain tumor research and drug development.
Over three days, presentations are given on some of the most promising research efforts in the field, as well as critical updates on many of the ongoing clinical trials for brain tumor patients.
Last week on the blog we highlighted a noteworthy update from this gathering – the Novocure clinical trial. Here we will dive into five more topics of note:
Old Treatment Gets New Life
PCV is a chemotherapy regime that includes the three drugs: procarbazine, CCNU (lomustine), and vincristine. The use of PCV in brain tumor patients goes back many years, but is less frequent in the years following the approval of temozolomide (Temodar), which subsequently became the standard of care for newly diagnosed high-grade glioma patients.
PCV may soon become a regular part of treatment for low-grade glioma patients (grade II), a group in which, to date, the appropriateness of using chemotherapy as part of upfront treatment had not been determined.
In a study presented during the opening plenary session of SNO, Dr. Jan Buckner of the Mayo Clinic revealed that PCV prolonged both overall survival (OS) and progression-free survival (PFS), compared with radiation therapy alone in a phase III study of patients with grade 2 gliomas.
The presentation was a long-term follow-up of the RTOG-9802 study, and data showed that patients who received PCV lived 5.5 years longer, on average, than those who received radiation alone. The study was done in 251 low-grade glioma patients who were deemed “high risk,” meaning they were 40+ years old and/or a sub-optimal percentage of their tumor could be removed.
The study suggests that PCV chemotherapy should now be a standard part of frontline therapy for these “high risk” low-grade glioma patients. The researchers’ next steps are to now further determine low-grade glioma subpopulations that benefit most from the treatment. Read more here.
Interim results from a number of ongoing clinical trials were presented from across the brain tumor field. Several of these trials showed strong early data. Here are just a few:
BELOB – Dr. Martin van den Bent of Erasmus University Medical Center in the Netherlands presented a final analysis of a phase II clinical trial called BELOB, which studied the use of the anticancer drug bevacizumab (Avastin) in combination with the chemotherapy lomustine in recurrent glioblastoma multiforme (GBM) patients, versus lomustine alone and bevacizumab alone. The results suggested that combining these two therapies provided a small, but significant, benefit to recurrent GBM patients, and warrants further trials. Read more here.
ReACT – ReACT is an ongoing, phase II study of Celldex Therapeutics’ vaccine, rindopepimut (an investigational immunotherapy), in a subgroup of recurrent GBM patients. The results, presented by Dr. David Reardon of Dana-Farber Cancer Institute showed that combining rindopepimut with bevacizumab prompted a strong immune response in EGFRvIII-positive recurrent GBM patients, and early indications of improvements in both PFS and OS. Patients with this mutation have historically had a very poor prognosis, especially following progression. A phase III trial is about to begin to confirm these results in a larger study. Read more here.
Toca 511 & Toca FC – Tocagen’s lead investigational compounds Toca 511 and Toca FC are designed to act in combination as a novel gene therapy and anticancer agent for high-grade glioma patients. The drug combination not only has direct effects on the cancer cells but also elicits an immune response to help attack the tumor. At SNO, Dr. Timothy Cloughesy of UCLA presented interim data that demonstrated increased median OS and PFS at six months for recurrent high-grade glioma patients treated with Toca 511 and Toca FC, versus historical benchmarks. The study is still early and will need to move into a randomized, controlled trial to confirm these positive initial results. Read more.
ICT-107 – ICT-107 is a dendritic cell-based immunotherapeutic vaccine produced by ImmunoCellular Therapeutics. Dr. Patrick Wen of Dana-Farber Cancer Institute presented data from a randomized, double-arm, placebo-controlled trial of ICT-107 in newly diagnosed GBM patients. The results showed that patients receiving ICT-107 had a statistically significant benefit in PFS over the control (placebo) arm. The study leaders suggested possibly moving ICT-107 into a phase III registration trial if final data from the study continues show improvement. Read more.
PVSRIPO – Researchers from Duke University presented final results from a phase I trial of their oncolytic Polio/Rhinovirus Recombinant, a unique immunotherapy approach that has received a great deal of attention recently. This oncolytic virus was tested against recurrent GBM, and early results showed a median survival of 12 months, but with some patients alive more than 20 or 30 months after treatment – far past historic benchmarks in this patient population. The therapy will now have to enter larger trials that are randomized and controlled to confirm its effectiveness and safety. Read more here.
A number of other trials with early, positive results were presented. Please check the SNO website for more information.
A big topic with multiple, related sessions and presentations at this year’s SNO was the molecular classification of brain tumors, specifically gliomas.
Currently, gliomas by-and-large are classified into grades (which affects diagnosis, prognosis, and treatment decisions) based on what’s called histopathology. In this paradigm, a pathologist examines a tissue sample from a patient’s biopsy under a microscope and produces a report on the tumors grade and diagnosis from an observable set of standard characteristics.
However, more and more studies over recent years are showing that genomics and molecular analysis of tumors can provide a deeper level of understanding of each tumor’s unique biology (and thus, again, better inform diagnosis, prognosis, and treatment).
This includes an important study presented at SNO by a team of researchers from MD Anderson Cancer Center who examined data from the Cancer Genome Atlas to re-classify low-grade gliomas. Using molecular markers that would not typically be incorporated into a low-grade glioma pathology report, the group found that a certain sub-group of what histologically look like low-grade gliomas, actually act more like the high-grade glioma, GBM. The implications, if confirmed, from this study are that low-grade gliomas with this molecular marker (IDH wild-type), should actually be treated like a GBM and not like a lower-grade glioma.
The discussion on classification continued through the weekend, culminating in a session on Sunday, “WHO and Molecular Classification Forum,” where leaders in the field discussed the challenges and opportunities of making molecular analysis a more standard part of classifying brain tumors. The group plans to continue dialog, including a survey of all SNO members, and present a report of information and recommendations to the World Health Organization (WHO), the group that sets the standards for tumor grading. Read more about this effort here.
Patient Experience at the Forefront
Addressing patients’ experiences was a key part of this year’s SNO meeting. This was clear from the outset of the conference, which began “Education Day” on Thursday (11/13) with a five hour “breakout session” on Quality of Life, and followed with a Saturday session on controlling epilepsy in brain tumor patients, and concluded with a two-hour session Sunday on “Patient Reported Outcomes and Neurocognition.”
Additionally, leaders of the Jumpstarting Brain Tumor Drug Development Coalition’s Brain Tumor Clinical Trial Endpoints Workshops held a session on Saturday to review the progress made on this initiative to date. This included a review of the recently completed Workshop on Clinical Outcomes Assessments, which discussed pushing to include more patient-focused measures in future brain tumor clinical trials (press release here).
The crowd received these efforts very well, including praise that the field was putting an ever-increasing emphasis on the patients’ experience during treatment.
Immunotherapy – A Running Theme
Immunotherapy, an emerging treatment method for brain tumors that seeks to harness a patients’ own immune system to fight their tumor, was a big topic at this year’s SNO (as it was at many conferences this past year across the oncology/cancer field).
As noted in the section above on clinical trials, many of the investigational treatments presented were some form of immunotherapy – mostly from the categories of what are known as an oncolytic viruses and tumor antigens.
However, many additional presentations and sessions focused on the larger picture of immunotherapies and their potential in brain tumors, including more recent efforts to use newer classes of immunotherapies against brain tumors.
The pervasiveness and excitement of this burgeoning treatment modality was seen in the call to action delivered by Victor Levin Lifetime Achievement Award recipient, Dr. Darell Bigner, who urged more focus on immunotherapies in his acceptance speech during Friday’s plenary session. Later that same night there was an industry-supported symposium on “Emerging Advances in Immune-Oncology,” followed by a well-attended “Immunotherapy Minisymposium,” which also served as a plenary session, on Saturday afternoon.
Immunotherapies offer hope as better treatments for brain tumor patients because of their potential to be less toxic than current therapies, as well as more universally more effective because many (though not all) do not rely on targeting any specific molecular pathway in tumors. However challenges remain, including the number of immunosuppressant mechanisms needing to be overcome for a new therapy to create a lasting treatment effect. These challenges and more were discussed at SNO, providing a great opportunity for leading researchers to share ideas on how to capitalize on the emergence on immune-oncology in the field.
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As a final note, one other reoccurring topic at this year’s SNO was neuro-imaging, a topic National Brain Tumor Society and other Jumpstarting Brain Tumor Drug Development Coalition members played a particularly crucial role in championing. We’ll have more on some exciting developments in the area of brain tumor imaging in the next couple of weeks.