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Printable Handouts
Navigable Slide Index
- Introduction
- Glioblastoma (GBM): outcome 2016
- Immunotherapy in oncology: coming of age
- FDA-approved cancer immunotherapeutics
- Inhibitory immunomodulatory molecules
- CTLA-4 & PD-1
- Anti-PD-1 & anti-PD-L1 studies
- Immunotherapy: outcome improvement
- Ipilimumab therapy for metastatic melanoma
- Will immunotherapy work for brain cancer?
- Is immunotherapy a "mission impossible"?
- Historical bias: the brain is immunoprivileged
- CNS immunoprivilege: fact, fallacy or in between?
- CNS lymphatics
- PD-L1 expression: glioblastoma
- Efficacy of immuno-modulatory antibodies
- GL261-luc glioma model - objective & study design
- “Established” GBM model
- Checkpoint blockade induces long-term survival
- “Advanced” GBM model: equally active
- Checkpoint blockade & immunologic memory
- Mechanism of therapy mediation (study design)
- Characterization of intra-tumoral immune infiltrate
- Tumor specific immune response in patients
- Immune escape of tumor cells
- GBM: complexity/redundancy/heterogeneity
- Will heterogeneity matter for immunotherapy?
- Mutation frequency across and within cancers
- Neoantigen mutations & passenger mutations
- Neoantigen load predicts reactivity & outcome
- Neoantigens & response to CTLA-4 blockade
- Neoantigens predict response to PD-1 blockade
- PD-1 blockade and colorectal cancer tumors
- Multi-valent GBM vaccines
- Personalized neoantigen vaccine (“NeoVax”)
- NeoVax: exploits intra-tumoral heterogeneity
- DFCI/BWH NeoVax: trial design
- DFCI NeoVax trial update: treatment status
- Immunotherapy for GBM: 2016
- Phase III Nivolumab vs. Bevacizumab for GBM
- Phase IB Pembrolizumab in advanced tumors
- Phase II study to evaluate MEDI4736
- MEDI4736: Study design
- Case study (SE: 64 yr old Caucasian female)
- Case study (SK: 61 yr old Caucasian female)
- Imaging: PD-1 immune checkpoint blockade
- iRANO criteria
- The basis for iRANO criteria
- iRANO algorithm for treatment decision making
- iRANO: integrate into existing RANO criteria
- Concerns regarding immunotherapy
- GBM immunosuppression tumor mechanisms
- Immunosuppressive mechanisms in GBM (1)
- Immunosuppressive mechanisms in GBM (2)
- Combination immunotherapy GBM studies
- Phase II study of Pembrolizumab
- Dual targeting of VEGF and immunotherapy
- Bevacizumab plus Ipilimumab in melanoma
- Combination anti-tumor immunotherapy
- NeoVax + anti-PD-1 trial schema
- Conclusions
- Acknowledgements
Topics Covered
- Immunotherapy in oncology
- CNS immunoprivilege
- Glioblastoma (GBM): complexity/redundancy/heterogeneity
- “Established” and “Advanced” GBM models
- Tumor-specific immune response in GBM
- Importance of heterogeneity
- Overcoming challenges for durable GBM benefit
- Neoantigen mutations
- Checkpoint blockade & immunologic memory
- GBM vaccines
- Personalized neoantigen vaccine (“NeoVax”)
- Immunotherapy response assessment in neuro-oncology (iRANO)
- Clinical trials in neuro-oncology
- Immunosuppressive mechanisms in GBM
- Combination anti-tumor immunotherapy
Links
Series:
Categories:
Therapeutic Areas:
Talk Citation
Reardon, D.A. (2016, February 29). Immune checkpoint blockade in CNS tumors [Video file]. In The Biomedical & Life Sciences Collection, Henry Stewart Talks. Retrieved October 12, 2024, from https://doi.org/10.69645/ANRT2402.Export Citation (RIS)
Publication History
Financial Disclosures
- Dr. Md. David A. Reardon has not informed HSTalks of any commercial/financial relationship that it is appropriate to disclose.
Other Talks in the Series: Immunotherapy of Cancer
Transcript
Please wait while the transcript is being prepared...
0:00
Hello, my name is David Reardon and I'm the Clinical Director of
the Center for Neuro-Oncology at the Dana-Farber Cancer Institute
in Boston, Massachusetts in the United States.
Thank you for joining us for this Henry Stewart Talk on
immune checkpoint blockade in central nervous system tumors.
0:19
On the first slide, I've summarized the outcome for patients with glioblastoma in 2016.
On the upper part of the slide,
we see the standard of care therapy for
newly diagnosed glioblastoma patients that include maximum safe surgical resection,
followed by radiation with daily temozolomide,
after which patients receive
five-day temozolomide adjuvant cycles every 28 days for 6-12 cycles.
We see on the right that the outcome with this standard of care,
which was established over 10 years ago,
leaves a lot of room for improvement.
The median progression-free survival is only about eight months for patients,
which means they're about two-thirds of the way through
their plan treatment and the average patient is already progressing.
Unfortunately, median survival is only about 15-18 months.
Inevitably, patients recur, and the historical outcome for
patients with recurrent glioblastoma is summarized in the lower half of this slide,
where we see data from a series of meta-analyses of
clinical trials conducted through
various cooperative groups in North America and in Europe.
What we see is that the outcome with
the salvage therapies utilized in these clinical trials,
which include various chemotherapeutic regimens,
biologically-based targeted therapies, and
a variety of other innovative strategies, unfortunately,
have yielded very poor outcome with
six-month progression-free survival rates typically, approximately 10 percent.
With the use of bevacizumab,
the prototypic VEGF blocking anti-angiogenic agent,
we can improve progression-free survival with a six month PFS rate of up to 40 percent.
But, this still leaves much room for improvement,
and unfortunately, bevacizumab does not improve overall survival.