Jan 24, 2019
Key Takeaways from the 2019 Gastrointestinal Cancers Symposium with Dr. Stephen Leong
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Welcome to the ASCO Daily News podcast. I'm Lauren Davis, and
joining me today is Dr. Stephen Long, associate editor of ASCO
Daily News.
Dr. Long is associate professor in the division of medical oncology
and is a translational researcher in the GI and developmental
therapeutics programs at the University of Colorado Cancer
Center.
Dr. Long, welcome to the podcast.
Thanks for having me. It's a pleasure to be here.
Dr. Long, you've just returned from the Gastrointestinal Cancers
Symposium. How was this year's event compared with previous
years?
First of all, I love you GI ASCO. I always find it informative. And
I love the format of the talks and presentation.
This year there was no significant practice changing presentations
like in years past. However, there were still some excellent
presentations and talks.
And what were some of the presentations that stood out to you?
There were some reports of a couple of clinical trials that sort of
intrigued me. One was KEYNOTE-181. This was a phase III study
comparing pembrolizumab monotherapy versus standard chemotherapy in
patients with local events and metastatic esophageal cancer in the
second line setting.
They reported a significant improvement in overall survival in
patients with PD-L1 combined positive score of greater than 10. And
these patients received 9.3 months overall survival compared to 6.7
months for those who received [INAUDIBLE] choice of chemotherapy,
which then consists of paclitaxel, docetaxel, or irinotecan.
In addition, pembrolizumab was better tolerated and had a better
safety profile.
What made it really intriguing was of the total 628 patients that
were enrolled in the trial, 64% of them had squamous cell carcinoma
of the esophagus, which is unusual, especially in a phase II
setting.
And even though the study had a statistic overall survival benefit,
in the squamous cell carcinoma cohort, there was a non-statistical
trend in overall survival of 8.2 months versus 7.1
respectively.
Pembrolizumab did boost the objective response rate compared with
chemotherapy in the PD-L1 CPS greater than 10 and a response rate
of 21.5% versus 6.1%. And then squamous cell carcinoma, it was
16.7% versus 7.4%.
That leads to a whole bunch of questions. One, should we improve
our PD-L1 scoring by including a CPX score greater than 10 and
making our predictions based off that? In addition, should
pembrolizumab expand its indications to include squamous cell
carcinoma, since presently in the United States, pembrolizumab is
only approved for adenocarcinoma.
Also, there were the reports of the phase II ROAR study, which was
looking at biliary tract cancers with BRAF V600E activating
mutations. And these patients received a combination of dabrafenib,
a BRAF inhibitor, and trametinib, a MEK inhibitor.
There were 33 patients. And they had an objective response rate of
42%. All of them with partial responses. And 7 of the 14 patients
with responses had the responses lasting more than six months. And
adding those with stable disease, they had reported a disease
control rate of 88%.
They looked at survival data. And the median progression free
survival in this cohort was 9.2 months with an overall survival of
11.7 months.
And to put this into context, usually second line biliary tract
cancers we rarely ever see survival being more than five months.
And these PFS and overall survival is very comparable to the first
line setting for gemcitabine cisplatin, where the original study
showed a PFS of eight months and overall survival of 11.7
months.
So this potentially could be another treatment option for people
with V600E biliary tract cancers.
And then there were the preliminary results of a single phase II
study at Memorial Sloan Kettering, which was evaluating
pembrolizumab in conjunction with trastuzumab HER2 antibody with
CAPOX and those with HER2 positive metastatic esophageal gastric
adenocarcinoma.
They had 32 patients with the overall response rate of 87%. They
reported three CRs and 25 partial responses. And then when you
factor in the stable disease, they had 100% disease control rate.
And all the patients had some degree of tumor regression. The PFS
were 11.4 months with an overall survival having not been met after
six months.
This is extremely exciting, and this has already led to the
development of a global phase III study, which will be known as
KEYNOTE-811.
That's great. That sounds very promising.
Were there any research presentations that you were interested
in?
Oh, yeah. There was a lot of great preclinical work. One of the
most intriguing was in pancreatic cancer, where the Canadians did a
study known as COMPASS, where they took advanced pancreatic ductal
adenocarcinoma, and these patients underwent whole genome
sequencing, as well as RNA sequencing of their tumors, prior to the
initiation of first line chemotherapy with either modified
FOLFIRINOX or gemcitabine and abraxane.
Treatment outcomes were then compared to their molecular
characteristics. The data suggests that chemotherapy differs
depending on the transcription features of the tumor.
So for example, the best survival data came out of those patients
with the classical ductal adenocarcinoma subtype that were treated
with FOLFIRINOX. And they had a median survival of 7.17 months.
And when they were compared to the basal-like subtypes and were
treated with FOLFIRINOX, they had a median progression free
survival of 2.5 months.
Now, patients with the basal-like subtype actually had a better
response to gemcitabine and abraxane, which had a PFS of 5.65
months compared to the classical subtype, where they had median
progression free survival of 4.93 months.
So in summary, those with the basal-like subtype actually had a
resistance for FOLFIRINOX. In addition, the researchers also
mentioned that GATA6 RNA expression significantly correlates to the
PDAC classic and basal-like molecular subtype. So it could actually
be used as a marker in determining subtypes. And all this put
together means that we could potentially identify patients who have
a better chance of responding to FOLFIRINOX versus gem abraxane in
the first line setting in pancreatic cancer.
And obviously there needs to be more work to validate this, but
this actually is quite intriguing.
Also, there was data from the amino scoring testing, which was
looking at its test in high risk stage 2 colorectal cancer
patients. And for those who are not familiar, patients with stage
colon cancer have a poor prognostic if they had a T4 disease, had
fewer than 12 lymph nodes removed, had a point differentiation
subtype, and also had evidence of vascular emboli, lymphovascular
invasion, perineural invasion, or actually had a presentation of
bowel obstruction or bowel perforation.
And these patients are often offered adjuvant chemotherapy
following curative resection due to their high risk of
recurrence.
The amino score test measures the density of CT3 positive T cells,
as well as cytotoxic CDH cells within and surrounding the tumor to
gauge the strength of the host immune response at a tumor site. So
therefore a high amino score indicates a high anti-tumor immunity,
which correlates with a low risk for disease recurrence.
And these investigators looked at 1,130 patients with stage two
colon cancers. And their conclusion for time to recurrence was
those with high risk disease with high amino scoring compared to
those with low risk disease had a very similar five-year survival
of 87.4% versus 89.1% respectively.
In contrast, if you have a high risk disease and a low amino
scoring, your five-year time to recurrence was only 72.2% in the
absence of adjuvant therapy. So this could potentially be used as a
prognostic tool for those who are high risk stage two in the
future.
What about education sessions? Were there any that caught your
attention?
So my favorite was the neuroendocrine session. Neuroendocrine, as
most people know, is a pretty rare disease population. However,
there has been significant advances in the past few years with new
drugs, new understanding of the biology, new diagnostic procedures,
as well as testing.
And it was a great panel of leading experts to help us navigate the
new landscape of neuroendocrine and understanding how we should be
approaching this. So that was my favorite session.
Were there any other takeaways that were important during the
symposium?
There were a few other presentations I thought that were quite
interesting. The Japanese presented their Prep-02 or JSAP-05
trial.
And this was the first study to ever demonstrate the efficacy of
neoadjuvant therapy in resectable pancreatic cancer. And their
neoadjuvant chemotherapy regimen was a combination of gemcitabine
with an oral drug S1. And they showed that it met its primary
endpoint of overall survival of 36.72 months in those patients who
received neoadjuvant therapy versus 26.65 months in those who went
from upfront surgery.
And for the Japanese, which tend to do upfront surgery followed by
adjuvant chemotherapy in the past, I think this may be a shift in
their paradigm, where this could be the new standard in Japan of
using neoadjuvant therapy prior to surgery.
Also, there was the oral drug trifluridine and tipiracil, which was
studied in a phase III metastatic gastric and GE junction
adenocarcinoma for those who have received two previous line of
therapies. And they were randomized to the drug versus placebo. And
it demonstrated a 2.1 survival benefit over placebo.
And their main concern was a lot of these patients end up getting
gastrectomies. But being an oral drug, could that affect its
efficacy? And it seems like this benefit was also seen in those who
had a gastrectomy versus those who didn't as well. So this
potentially could be another option for those in the third line
setting for gastric cancer.
However, the big debate is even though it met its overall survival,
is 2.1 months clinically significant? And I guess we'll have to
have more data regarding safety and tolerability before we can make
that decision.
There is also the French GRECCAR-6 trial, which was evaluating the
optimal time to surgery following chemoradiation for rectal cancer,
where patients who underwent neoadjuvant chemoradiation were
randomized to waiting 7 or 11 weeks prior to a mesoresection of the
rectal cancer.
They demonstrated that they had very similar path CR rates between
the two. But more interesting, they found that if you had a good
disease response to chemoradiation, there was no difference in
disease free survival if you waited 7 weeks versus 11 weeks prior
to surgery.
However, if you were a bad disease responder, you had a poorer
disease free survival if you waited more than seven weeks. However,
this was not statistically significant.
And then the authors concluded that we shouldn't be waiting more
than seven weeks prior to surgery following neoadjuvant
chemoradiation for rectal surgery.
Thank you so much.
Again, today my guest has been Dr. Stephen Long. Thank you for
being on our podcast today.
And to our listeners, thank you for tuning into the ASCO Daily News
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