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Printable Handouts
Navigable Slide Index
- Introduction
- Topics of discussion
- HER2 and colorectal cancer
- HERACLES: treatment
- HERACLES: consort diagram
- HERACLES: responses by HER2 IHC score
- HERACLES: time to progression by HER2 score
- MyPathway: statistical plan
- Trastuz/pertuzumab in HER2+ mCRC
- Efficacy: summary of cancers with HER3
- HER2 as negative predictive biomarker: methods
- HER2 as negative predictive biomarker: outcomes
- Take home points
- BRAF mutated colorectal cancer: distinct biology
- BRAFm CRC: poor prognosis
- FOLFOXIRI + Bev improves PFS
- Vemurafenib: not effective in BRAFm CRC
- Dabrafenib + trametinib: limited activity
- Rationale for BRAF/MEK + EGFR (1)
- Vemurafenib/cetuximab/irinotecan in BRAF mCRC
- Demographics & safety
- Favorable response rate & PFS
- S1406: Cetuximab + Irinotecan ± Vemurafenib
- MEK116833 Phase 1/2 study
- MEK116833 Phase 1/2 study design
- Demographics and disease characteristics
- Safety profile
- Confirmed best response in BRAF V600E cohort
- Efficacy based on most recent interim analyses
- ctDNA: acquired mechanisms of resistance
- Targeting cancer stem cells
- Normal vs. cancer stem cells
- Therapeutic implications of cancer stem cells
- Pathways deregulated in cancer cells
- Contribution of STAT3 pathway to cancer
- Napabucasin is a cancer stemness inhibitor
- Preclinical effect on CRC stem cells
- FOLFIRI + BBI608 in mCRC: demographics
- Adverse effects related to FOLFIRI + BBI608
- Radiographic response FOLFIRI/bev + 608
- BBI608 + Gem/abraxane pancreatic (1)
- BBI608 + Gem/abraxane pancreatic (2)
- Summary
Topics Covered
- HER2 and colorectal cancer
- BRAF mutated colorectal cancer
- Targeting cancer stem cells
Links
Series:
Categories:
Therapeutic Areas:
Talk Citation
O'Neil, B.H. (2017, May 29). Novel treatments for GI malignancies [Video file]. In The Biomedical & Life Sciences Collection, Henry Stewart Talks. Retrieved December 14, 2024, from https://doi.org/10.69645/YFBL1101.Export Citation (RIS)
Publication History
Financial Disclosures
- Prof. Bert H. O'Neil has not informed HSTalks of any commercial/financial relationship that it is appropriate to disclose.
Other Talks in the Series: Cancer Therapies in the Personalized Medicine Era
Transcript
Please wait while the transcript is being prepared...
0:00
Hello, my name is Bert O'Neil.
I'm a medical oncologist,
Professor of Oncology
at the Indiana University,
Simon Cancer Center in Indianapolis.
I'm pleased today to talk to you
about the topic
of Novel Treatments for GI Malignancies.
0:17
These are the topics
I've chosen to discuss today.
Obviously, new treatments of any cancer
can be a very broad area,
so I've picked a few
that I think are of current relevance.
These mostly relate to colorectal cancer
although some of what I'll speak about
relates to other GI malignancies as well.
Note that I have specifically
not chosen to talk about
immunotherapies today and believe
this will be covered in other lectures.
So the topics we will discuss
are HER2 and colorectal cancer.
We'll speak about what strategies
are being developed
for dealing with BRAF mutant
colorectal cancer.
And lastly, a new area
of cancer biology
which is, can we target stem cells
to treat GI malignancies.
1:03
HER2 overexpression is uncommon
but is seen in colorectal cancer.
In the largest study of this to date,
strong membranous staining
for HER2 was seen in only 25 of 1900
or 1.3% of stage II-III tumors
and 29 of 1300 or 2.2% of stage IV tumors
in a collection
of randomized clinical trials.
Interestingly, HER2 overexpression
is strongly associated with KRAS
and BRAF status.
For example, in the stage IV tumors,
HER2 positivity was seen in
5% of KRAS/BRAF wild-type cases,
versus only 1% of KRAS/BRAF mutant tumors.