Practice Update | Onology

CONFERENCE COVERAGE 18

Significant updates in glioblastoma Interview with Patrick Y. Wen MD

presented the results of a randomized study looking at a personalized peptide vaccine in recurrent glioblastoma. Unfor- tunately that trial didn’t improve survival, although there were subsets of patients where the outcome may have been slightly worse in specific subgroups. And I think this goes to the issue of whether the best time to do immunotherapy trials may be in the first-line setting, where the immune sys- tem of the patient is more robust. A second immunotherapy approach uses an oncolytic virus. DNAtrix has an onco- lytic virus that not only replicates in tumor cells and produces tumor cell kill, it also develops an immune response, and that immune response also contributes to the anti-tumor effect. So, they looked at the combination of the virus with gamma inter- feron and they saw some responses, but the gamma interferon was not very well tolerated. But I think the next step combin- ing the virus with a PD-1 antibody is a very promising approach. That trial is ongoing. And then the third approach, using check- point inhibitors is a follow-up on the results of

Dr Jennifer Caudle speaks with Dr Wen, Director of the Center for Neuro-Oncology at the Dana-Farber Cancer Institute and Professor of Neurology at Harvard Medical School in Boston, on the INSIGhT trial and studies on immune-based therapies for CNS malignancies presented at ASCO this year.

Dr Caudle: I first want to talk about INSIGhT. Do you think INSIGhT represents a new paradigm for clinical trial design for CNS malignancies? Similar designs have been used in more common malignancies such as breast, so how successful do you think this approach will be with CNS tumors? Dr Wen: INSIGhT is biomarker-driven adap- tive design trial and it’s somewhat similar to the I-SPY trial in breast cancer. The whole idea of those types of trials is to accelerate the development of novel agents. They use basin algorithms to take into account the outcome of each patient. So that informs the arms that are not successful so that they can be dropped sooner. As the trial progresses, those patients that are benefitting from

specific arms will be randomized to those arms, and those arms will graduate sooner. So, I think we’re hoping that these types of trials will speed up the way we develop new therapies for brain tumor patients. Right now it’s in glioblastoma, but potentially it could be in all other types of brain tumors. Dr Caudle: Multiple immune-based therapies for CNS malignancies are being presented this year at ASCO 2017. Could you review some of this key data for us? Dr Wen: At this meeting there were three types of immunotherapies. There were vaccine therapies, oncolytic viruses that also generate an immune response, and checkpoint inhibitors. A Japanese group

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