Top Takeaways from ASCO: Neuro-oncology

Issue: August 10, 2015

CHICAGO – Neuro-oncologists were buoyed by findings revealed within their subspecialty at ASCO 2015, with potentially practice-changing research presented in the plenary session, as well as in a clinical science symposium and an oral abstract session on central nervous system tumors.

In addition to the cognitive risks of whole brain radiation, attendees learned the effects of immunotherapy in targeting brain tumors, particularly glioblastoma — the most common type and the same that took the life of Senator Edward Kennedy.

Manmeet Ahluwalia, MD, director of the Brain Metastases Research Program at the Cleveland Clinic and neuro-oncology section editor for HemOnc Today, and Vinay Puduvalli, MD, director of the neuro-oncology division at the Ohio State University Comprehensive Cancer Center, share the Top Takeaways of these results and discuss how they could impact clinicians every day in practice.

Results from NCCTG N0574

During the plenary session packed with crowds filling two spillover rooms, Paul D. Brown, MD, of the University of Texas MD Anderson Cancer Center, reported findings from patients with one to three small brain metastases randomized to stereotactic radiosurgery alone or with whole brain radiation.

“The addition of whole brain radiation to stereotactic radiosurgery led to better control of the brain metastases; however, this did not translate to overall survival benefit in these patients,” Ahluwalia told Healio.com.

Manmeet Ahluwalia

Although the improved control with whole brain radiation and the lack of between-group difference in survival were both expected, the findings on recall, memory and verbal fluency were revelations.

“The additional piece of information was the patients who received whole brain radiation therapy did have worsening of cognitive function,” Puduvalli told Healio.com.

Patients with one to three small metastases (< 3 cm wide), most with primary lung cancer, underwent cognitive testing before and after each treatment. Cognitive progression, defined as a decline of more than one standard deviation from baseline to 3 months in any of the six cognitive tests, served as the primary endpoint.

More patients with whole brain radiation experienced progression at 3 months vs. those with radiosurgery (92% vs. 64%). The whole brain radiation cohort experienced greater declines in immediate recall (30% vs. 8%; P = .0007), delayed recall (51% vs. 20%; P = .002) and verbal communication (19% vs. 2%; P = .02).

“The authors of this study felt that patients who have one to three brain metastases should be offered stereotactic radiosurgery alone in an up-front setting,” Ahluwalia said.

Puduvalli underscored that despite this standard-of-care recommendation for this population, whole brain radiation is still the best choice for patients with six to eight metastases.

“Patients with microscopic metastases could have neurocognitive dysfunction from the tumors themselves, so what you think you’re salvaging by not giving the radiation, you might be causing because the tumors grow back,” Puduvalli said. “We don’t know which subsets those are and how to identify them yet. That group may still benefit from radiation.”

There is also new evidence that specialized planning for whole brain radiation with hippocampal sparing may reduce the cognitive deficits without compromising disease control, Puduvalli noted. Whether this will help get the balance between better disease control in the brain and preserved neurocognitive function is another area of study.

“With such data, we may end up not generalizing the results of the current study to everybody,” Puduvalli said.

Tumor treating fields and EF14

In the oral abstract session, Roger Stupp, MD, of the University Hospital Zurich and University of Zurich, Switzerland, presented data on tumor treating fields in addition to standard-of-care radiation and chemotherapy and temozolomide in patients with newly-diagnosed glioblastoma.

“There was an improvement in PFS and OS in patients who were treated with this experimental therapy that delivers alternate electric fields to the tumor,” said Ahluwalia, who chaired the session. “The study actually showed there was no additional toxicity seen in the experimental arm, and quality-of-life and cognitive function was preserved in these patients.”

Patients received adjuvant chemotherapy alone or with the antimitotic treatment modality — delivered by a portable, home-use medical device — after concomitant chemoradiotherapy.

The primary endpoint was PFS, with OS, safety, cognitive function and quality-of-life serving as secondary endpoints.

PFS was 7.1 months with the tumor treating fields vs. 4.2 months with temozolomide alone (HR = 0.694; 95% CI, 0.558-0.863), and respective OS was 19.4 months vs. 16.6 months (HR = 0.754; 95% CI, 0.595-0.955). The data translates to 2-year survival rates of 43% vs. 29%, with no real added toxicity seen with the heat-shock protein and comparable quality-of-life and cognitive function between groups.

“The final results of this trial with all patients included look very promising and, once published and reviewed by the FDA, may potentially provide a new standard of care for our patients in the U.S.,” Puduvalli said. “The discussion regarding the results did raise the question of crossover of patients to the experimental arm after tumor progression on the control arm; however, this may not have a major impact on the results.”

Vinay Puduvalli

The results present an additional option to treat patients with newly-diagnosed glioblastoma, Ahluwalia said, noting the community eagerly anticipates further results.

“We are awaiting the publication to see more details about the subset of patient population that derived the greatest benefit from the therapeutic modality,” Ahluwalia said.

Results from ReACT

David A. Reardon, MD, of the Dana-Farber Cancer Institute, Boston, Mass., reported in the clinical science symposium near-final data in patients with relapsed glioblastoma randomized to bevacizumab alone or with the investigational rindopepimut.

Bevacizumab, which targets blood vessel growth, is the current standard-of-care in this subset of patients. Rindopepimut is a peptide sequence unique to EGFRvIII delivered subcutaneously.

“Between 25% and 30% of patients harbor EGFRvIII, which is a constitutively active EGFR deletion driver mutation associated with poor survival in glioblastoma,” Ahluwalia explained.

Compared with bevacizumab alone, adjunct rindopepimut improved PFS at 6 months (27%, or 9/33 patients vs. 11%, or 4/35 patients) (P = .048).

“The results were very interesting in that the control of the disease without growth for at least 6 months actually reached the statistical significance that the authors had set forth in the study,” Puduvalli said. He called the OS benefit with the vaccine vs. control “more surprising.”

“Although OS was not the primary endpoint of the study, and hence should be taken with a bit of caution and cannot be translated into therapy, it’s a very promising result that suggests immunotherapy can be combined with anti-angiogenic therapy in patients who have glioblastoma that go back, [SP1] and we hope that this will lead to a bigger trial soon.”

Ahluwalia said the community is eagerly awaiting the results of the ACTIV trial, a phase III trial evaluating rindopepimut with standard-of-care chemotherapy and radiation in 700 patients with newly-diagnosed glioblastoma.

“The results of the current study show that this may be an exciting new therapeutic option for these groups of patients,” said Ahluwalia.

References:

Brown PD, et al. Abstract LBA4.

Stupp R, et al. Abstract 2000.

Reardon DA, et al. Abstract 2009.

Presented at: ASCO Annual Meeting; May 29-June 2, 2015; Chicago.

Disclosure: Ahluwalia reports consulting for, and or receiving honoraria from Caris Lifesciences, Elekta, Genentech/Roche, Incyte, Monteris Medical and Novocure. Puduvalli reports serving on advisory boards for Foundation Medicine, Genentech, Nectar Therapeutics, Orbus Therapeutics and Plexicon.