Dr. Kunle Odunsi discusses the latest breakthroughs and future promise of immunotherapy for ovarian cancer patients. #CRIsummit #immunotherapy …
(upbeat music)
– Welcome back, now it's
my pleasure to welcome
and introduce our doctors specializing
in ovarian cancer and immunotherapy,
Dr. Kunle Odunsi.
Dr. Odunsi is joining us
from the Roswell Park
Comprehensive Cancer Center,
Buffalo, in New York.
At Roswell Park,
Dr. Odunsi is the chair of the department
of gynecologic oncology as
well as the executive director
of the center for immunotherapy.
He's also an associate director
of the Cancer Research Institute
Scientific Advisory Council.
Thank you Dr. Odunsi
for being here with us
and answering our questions
about cancer immunotherapy
for ovarian cancer.
A cancer, that affects
more than 200,000 women
worldwide each year.
We also have with us Brian Brewer
from the Cancer Research Institute,
who will be sharing your
questions with Dr. Odunsi.
So please be sure to put
them in the Q and A box.
– Well, thank you very much
for the introduction, Tamron.
I'm very pleased to be on
this program this morning,
actually it's afternoon.
And thanks to CRI for
putting this together.
It's really a wonderful
opportunity to update ourselves
about some of the recent advances
in ovarian cancer immunotherapy.
So what I plan to do today
really is to focus primarily
on some of the next generation strategies
for ovarian cancer immunotherapy.
And I've listed three aspects.
One is the use of
adoptive T cell therapies.
Number two is the use
of neo-antigen vaccines.
Number three is…
Really I'm trying to understand
who will best respond to
immunotherapy in ovarian cancer.
So before I go on to the next slide,
let me just quickly
highlight the strategies
for immunotherapy in general.
As many will know on this call,
that there's the use of cancer vaccines,
the use of immune checkpoint inhibitors,
and really those are the most popular type
of immunotherapies.
Then there is the use of another strategy,
which I may touch upon as you
know, during this discussion,
the use of oncolytic viruses,
these are viruses that are
unique in their ability.
So selectively destroy cancer
cells and spare normal tissue.
And then the real question
is, who is going to respond?
How can we identify those
who are going to respond?
One of the areas that we
and others have focused upon
is this aspect of using the T cells.
T cells had been major cells
that kill cancer cells.
And so our current generation
approaches for using T-cells
involve taking the blood,
taking blood from a patient,
taking it to a special lab
engineering those T cells,
those immune cells,
and generating large numbers
to give back to patients.
Many will be familiar with CAR-T cells.
That's an example of T cells
used for adoptive T cell therapies.
And as we all know, they
have been very successful
for treating liquid tumors, some leukemia
and some lymphomas, but not
so much with solid tumors,
including ovarian cancers.
So the current generation of T-cells
essentially we're asking these T-cells,
these immune cells to arrive in the tumor
and be able to do their job.
And yet they face combat
attack by the cancer cells.
So that is really what's going on
because the area of the tumor,
you can imagine that
it's like a battle ground
between the T cells and the cancer cells.
So some of the new generation approaches
involve putting a shield
around the T cells
so that they can resist
counter-attack against the tumor.
And there are ongoing clinical trials
testing these approaches at Roswell Park
and in other cancer centers,
where in fact, the T cells are stronger.
They're able to persist
longer and be able to survive
and resist counter-attack by the tumor.
So I will like to talk about
personalizing immunotherapy.
There are really two aspects of this.
In the beginning,
I talked about the new
antigen vaccine approach,
because one of the fundamental
features of the immune system
is to try and discriminate
between self and non-self.
And that's why the immune system
has no trouble fighting off
bacteria and viruses.
So if you give a flu shot, for example,
the immune system knows that
the flu virus is foreign
when it sees the virus the next time
it's able to go on the attack.
So the question is
what discriminates a cancer
cell from a normal cell?
And one of the discriminating factors,
actually the mutations
in the cancer cells.
And so one approach that is
called neo-antigen vaccination
is to take the information,
the knowledge of the mutations
in the cancer,
and use that to construct
personalized vaccines
for patients.
So this has been tested
in several institutions
across country now,
and it allows the ability
to tell out a vaccine,
to personalize a vaccine
towards a specific patient.
The other aspect of personalizing therapy
is to really understand
what is going to work best
for a particular patient.
And so this requires
developing biomarkers,
biomarkers are tests
that can predict potential responsiveness.
At Roswell Park for example,
we came up with what we
call immune report card,
which is a panel of about 300 genes
that relate to the immune
system that allows us,
for example, to trans select
the best possible immunotherapy.
Because if you recall,
not all immunotherapies are the same
and not all immunotherapies
will work in each
and every patient.
So it's going to be important to select
the best type of immunotherapy
for each particular patient.
And I'll stop there and take questions.
– Thanks again, Dr. Odunsi for being here,
it's always wonderful to see you.
You're an associate director
of our Scientific Advisory Council,
and I've enjoyed working
with you for so many years,
so good to see you.
So let's get right into these questions.
I'll just remind folks who are watching.
You can continue to leave
your questions in the Q and A.
We will try to get to as
many of them as possible.
If we don't get to them all today,
we will follow up in a blog
post after today's events.
So, first question, Dr. Odunsi.
Doesn't ovarian cancer patient
have to undergo chemotherapy
before receiving immunotherapy?
– So chemotherapy, as we all
know is the standard of care.
So the standard of care for ovarian cancer
is surgery followed by chemotherapy,
and more recently followed by some forms
of maintenance therapies.
It is not required to get
chemo before immunotherapy,
because in fact, in some settings,
chemotherapy might help the
ability of immunotherapy
to work better, so it is not required.
In fact, several studies
over the last couple of years
have combined chemotherapy
with immunotherapy.
Some of them with modest benefit,
those results have not been
significantly positive,
but there are patients who
benefit from those combinations.
– For a lot of patients who are
learning about immunotherapy
for the first time,
or I've heard all the
stories about chemotherapy
for as long as that's been around,
it might sound counterintuitive
that giving chemotherapy
could help the immunotherapy work more.
So can you tell us a little
bit about how that happens?
– So some chemotherapies
able to kill cancer cells
in a particular way.
And it turns out that the way
in which it cancer cell dies
can have implications
for the immune system.
That is a form of cancer cell death
that can actually
activate the immune system
and thereby increase the potential
benefit of immunotherapy.
So that's how the two can work.
And so that's a great question for years
we thought chemotherapy
is immune suppressive,
but in fact, depending on how you use it,
chemotherapy can help immunotherapy.
– That's fascinating
and learning about combination therapies
and how things can synergize,
I have better effect
on patient it's just
great fascinating stuff.
Next question from an audience
member about cancer vaccines.
What cancer vaccines are
available for ovarian cancer
are being studied in ovarian cancer?
– So there are two broad
categories of cancer vaccines
that are available.
The first category of
cancer vaccines against
what we call shared antigens.
These are proteins that are
expressed on cancer cells
that potentially are not
expressed by other normal tissue.
And there are very few of those.
In fact, if you dig deep,
there are only very small number.
And one of the key ones
is the protein discovered
at the Ludwig Institute
for Cancer Research called NY-ESO-1.
And why?
Because it was discovered
in New York city.
Initially in a patient
with cancer of esophagus.
So we and others have tested this vaccine
across a broad category of patients.
And although we see
some signal of efficacy
that it works.
We're able to induce immune responses.
And in fact, some patients
have prolonged remission,
it's not sufficient.
So cancer vaccines need to be combined
with other strategies.
The second major type of cancer vaccine
is the use of this new antigen
vaccines that I talked about
that relies on the mutation in the cancer,
in order to create the vaccine.
So those are the two broad categories
where you are either
targeting a shared antigen
or you're targeting a new antigen.
– So I'm going to skip ahead
since you bring up again,
you know, the sequencing
and identification of either personalized
or shared antigens here,
and it kind of gets back
to the immune report card
that you spoke about that
you have at Roswell Park.
How does a patient no task,
or must a patient be proactive and asking
for this type, it's called
sequencing, genomic sequencing,
and who does a patient ask for that?
Or is it just standard?
Is it just going to happen?
– Those genomic sequencing
testing at the present time
are not standard.
So I think it's important
for a patient to ask,
but many cancer centers
around the country,
it's almost automatic.
You know, many cancer centers
have molecular testing program
or personalized medicine programs.
And so it may be standard
in many cancer centers,
but I think it's important for
the patient to be proactive
and ask your doctor about
getting some of this testing.
– Are those tests a
part of a clinical trial
or are they part of a
patient's standard treatment?
– So those tests
have actually now become
part of standard treatment.
So for example, in ovarian
cancer, it's very important
for us to know whether a patient
has a BRCA mutation or not,
because that has tremendous implications
for all kinds of treatment
plan that we make
and BRCA mutation can also,
you know, the BRCA type
mutations can also help us
in planning treatment.
So it's automatic for us now
in ovarian cancer patients
in many institutions to
get this genomic testing.
– Speaking of mutations,
let's talk about Lynch
syndrome for a moment.
We heard yesterday from our patient,
one of our patient
panelists, Stephen Estrada,
who had colorectal cancer,
having Lynch syndrome,
made him more likely to respond
to checkpoint blockade immunotherapy.
And of course he fortunately
had a complete response.
Is the same situation,
or does Lynch play a role
in ovarian cancer patients?
And do you see and if so,
any similar responses?
– We actually do not see a
lot of Lynch syndrome patients
developing ovarian cancer.
They are more likely to
develop uterine cancer,
endometrial cancer, and
in endometrial cancers,
when they develop, when
they have Lynch syndrome,
they have what we call
microsatellite on stable tumors.
Those are very responsive
to immunotherapies.
In fact, there has been
a lot of FDA approvals
for the use of immunotherapy for patients
with Lynch syndrome or
microsatellite on unstable tumors,
across many concept types.
In the field, ovarian cancer
patients, where we see MSI,
microsatellite unstable tumors.
Those patients may also
benefit from immunotherapy,
but there are very few numbers.
– What about patients
with autoimmune diseases?
What special considerations
go into play for them?
– In patients with autoimmune diseases,
the use of immunotherapy
has to be considered very carefully.
Traditionally many clinical trials,
those patients have been
excluded in clinical trials
because of the potential
for many immunotherapies
to cause autoimmune side effects.
It can affect the thyroid
gland, the pancreas,
the adrenal gland, almost
any organ system in the body.
I said, you know, can have side
effects from immunotherapy.
So if you already have
preexisting autoimmune disease,
it's going to be important
to consider the severity
of the autoimmune disease,
which organ is it affecting
and work with your doctor
to see whether or not
you might still be able
to receive immunotherapy.
In many instances for us,
if the auto immune disease
is well controlled,
we walk with the patient to
try and see whether we can try
to still use immunotherapy
paying very careful attention
to the potential for this side effects.
– Let's talk about PARP
inhibitors and a combination
with immunotherapy.
Are those taken sequentially together?
Can patients be on those indefinitely?
– PARP inhibitors have
actually made a major impact
in ovarian cancer therapy
over the last few years.
In fact, new guidelines,
patients who are ovarian,
all ovarian cancer patients essentially
can go on maintenance
therapies with PARP inhibitors.
Or the patients who are most likely
to benefit a patients with BRCA mutations
or patients with what we call HRD,
homologous recombination deficiency,
BRCA type, phenotype.
Those patients benefit
from PARP inhibitors
and it appears as if
they also benefit more
from immunotherapy.
So it makes sense to combine.
And when we combine, we tend
to use them concomitantly.
Some of the results indicate
that the response rates
are better for patients
receiving the combination,
but there is still a
large majority of patients
who are not responding.
And one of the major areas
of research is to understand
what are the additional
factors that will predict
who's going to respond and
who's not going to respond.
– And what are some of
those factors again?
It's pretty, this is
complicated to all squeeze into,
you know, the short
amount of time we have,
but if I'm a patient and I'm considering,
you know, entering a
clinical trial, for instance,
what might be some of those factors?
I think we're still getting that question.
So if we can just go
over that again, briefly.
– So someone of those factors
include the intrinsic.
So the property of the tumor itself,
so ovarian cancers are cancers
without a high mutation burden.
So they tend to be not
responsive to immunotherapies
in general.
So if you look at clinical trials
of single agent immune
checkpoint inhibitors
in ovarian cancers,
the results have not been very impressive.
We see response rates in
the range of maybe 5 to 15%.
So it's going to be important
to combine with something.
And that is really going
to require overcoming
some of the mechanisms of
resistance that so many of them,
there are immune cells for example,
within the tumor that
actively suppress the T cells,
the T cells are the most critical.
So you have other immune cell populations
that are frequently
present in ovarian cancers
that can suppress the T cells.
And then you have ovarian
cancer making some additional
like chemicals that can
suppress the T cells.
So I think the more we
understand these, you know,
these aspects of ovarian cancer,
the more we can better target.
So for example,
one recent study from our
institution shows that the Osiris,
okay, the fluid that is produced
by ovarian cancer itself
is highly immunosuppressive.
So you can imagine if you give, you know,
the immune checkpoint
inhibitor immunotherapy
in a patient who has Osiris
the fluid sitting in the abdomen,
when the T cells get to the tumor,
you can imagine that it's
going to suppress the T cells.
– So what about other types
of gynecologic cancers,
do you see the same
thing in cervical cancer
or endometrial cancers, uterine cancer?
– Cervical cancer is
a little bit different
because we know what causes the majority
of cancer of the cervix,
human papilloma virus.
So because of that,
cervical cancer is actually
have higher mutation burden
compared with ovarian cancer, for example,
and it's been more responsive
to immune checkpoint inhibitors.
Uterine cancers is significant
proportion, have this MSI,
microsatellite instability,
which is part of the Lynch syndrome.
And therefore they respond to
immune checkpoint inhibitors.
In fact, the uterine cancer,
there's a group that has
what we call ultra-mutated.
They have tons of mutations
and they are very highly responsive
to immune checkpoint inhibitors.
So the bottom line is that any patient
with gynecologic cancer should be asking
their treating physician
about some of these genomic
testing, sequencing testing
in order to understand
the nature of the cancer
and select the most appropriate therapy.
– Let's talk about TMB
again, tumor mutation burden,
what causes that?
And what does that imply for a patient
who's considering treatment
with immunotherapy?
– So the tumor mutation
burden is simply asking,
what are the genetic
alterations in the tumor?
What is the frequency?
And the more the mutations,
the more you are like,
the cancer cell is going to be
different from normal tissue,
from normal cells
and therefore the more the immune system
is going to likely
recognize them as foreign.
So you can imagine
if now use any new checkpoint inhibitors,
you can generate immune cells,
T cells against this foreign cancer cells.
In ovarian cancer there's
not a lot of mutations.
The major driver mutation
is a gene called p53.
Other than that, you
see very few mutations.
What you see in ovarian cancer
is what we call copy number variation,
where the chromosomes are very abnormal,
but you don't naturally
see a lot of mutations.
Therefore, it's not that
immune checkpoint inhibitors
cannot work, we think that can work.
A, we need to select which
patients in which patients
are they going to work in.
And secondly, we need
to find other approaches
to change the environment
of the ovarian cancer,
so that there are more T
cells so that, you know,
it becomes more conducive
to immunotherapy.
– We have another question again,
I'll remind all of you watching
to please leave your
questions in the Q and A.
We certainly won't get
to all of them today,
but we will be following up after today.
So, please do share your questions
and we'll get them to Dr. Odunsi.
One question we have has
that has come in is age
and whether or not that's a
factor in a patient's response
to immunotherapy.
What can you say about that.
– Fast of all we fought
for the longest time,
we used to think that
patients who are older,
are unlikely to respond to immunotherapy,
similar to how we used
to think about, you know,
chemotherapy and immunotherapy
is become clear that patients
even older patients can respond
very well to immunotherapy.
If you recall, one of
our former presidents
responded very well to immunotherapy
when he had metastatic melanoma.
So age is not a barrier,
providing someone is healthy
and it's appropriate to treat that patient
with immunotherapy.
– That's really good to hear,
because I'm not getting any younger.
(laughing)
Any advice you give to
patients on how to stay healthy
so that they can respond
well to treatments.
So diets and nutrition is
something we get often asked.
Anything you might say to
the patient about that.
– I think diet, nutrition
and physical exercise
are very critical.
We did a study recently at Roswell Park,
where we led by one of my
colleagues, Dr. Emese Zsiros,
where she looked at the
physical activity of women
with ovarian cancer.
Using a Fitbit, you know,
we attached Fitbit to this patients
and simply asking the question,
how many steps do you take a day,
as well as recording the
heart rate and blood pressure
and all of all of those things?
What we found is that the
majority of our patients
actually take very few steps,
even though they considered
themselves active,
you might argue it's because they are sick
therefore, they are like,
you know, what you expect?
Therefore they're unlikely
to, you know, to be active.
But to the extent possible,
if physical activity can be increased,
this may actually have
significant implications
for the immune system.
And this has been shown in you
know, in some other studies.
So that is one advice.
The second advice actually
relates to therapy,
making sure the patient is
asking the right questions
from their doctors, asking
about clinical trials.
What clinical trials are available
and why select one clinical
trial over the other?
Are there special tests
that need to be performed?
You know, that's a
selective clinical trial.
Those kinds of questions
are very critical.
Let me add one more aspect
that I touched on very briefly
in the beginning and that is
the use of oncolytic viruses.
These are viruses that are very powerful.
They are engineered to
selectively destroy cancer cells
and spare normal tissue.
The major benefit of these viruses
is that they can overcome
many of those mechanisms
that we talked about
because they can directly
destroy cancer cells.
And then they send a
danger signal all around.
So say that's danger here, immune system,
you got to come on and fight.
And when that happens,
the immune system is called to action
and begins to fight the cancer cells.
This virus is can also
be used to deliver cargo
into the tumor.
And we and others have begun
to engineer these viruses
so that they can deliver
some drugs or some approaches
into the tumor environment
and make it even better
to respond to immunotherapies.
– It's really amazing,
but what research makes possible
that we've gotten this far
and that we seem to be accelerating
at a never faster pace,
and so it's so more important than ever
to keep the research going.
One question we also get
from some audience members
is let's say they've received
one type of immunotherapy.
They may or may not respond to it.
Does that make them ineligible
to receive another type
of immunotherapy or can they consider
going into another trial or
receiving another treatment?
– So the short size they
can receive another type
of immunotherapy,
but I think it's important
for the treating physician
to understand what is the,
again, I go back to the testing.
What, is the most likely
immunotherapy that the patient
is going to respond to?
Because again,
immunotherapy is not just one type,
there are different
types of immunotherapies.
So it's going to be
important to think through
what is the next best approach
for that particular patient.
And that may depend on some of the testing
that we've talked about already.
And this patients may be
put on other clinical trials
testing other approaches
of immunotherapies.
So had been on one type of immunotherapy
does not preclude going on
other types of immunotherapies.
– One really, good
metaphor I heard for this
is kind of the Lily pad theory
where you just want to get
onto that next lily pad.
And you never know what's
going to come down the road.
There may be another treatment
in development pipeline,
just waiting on the horizon.
You can just get to that
next, you know, Lily pad.
So let's talk about the future
briefly, because as I said,
it seems like we're approaching it faster
than ever before.
What do you see about the
future of immunotherapy
for ovarian cancer, uterine cancer?
And do you ever think
it's going to completely
supplant chemotherapy
or radiation therapy or will
we always see combinations?
– I think the future for ovarian
cancer is going to require,
again, this whole concept
of generating a large number
of immune cells, the T cells,
and that can be done using the
vaccines that we talked about
and then using checkpoint inhibitors.
So we're going to have
combinations going forward.
And the combination again,
will be combination of
immunotherapies themselves,
vaccine plus checkpoint,
adoptive cell therapy plus checkpoint.
And then somewhere in the mix
was to going to use chemotherapy,
but we're going to be using it
at a much less, either less dose
of chemotherapy or much less
frequency or less duration
of the use of chemotherapies
as immunotherapies
as we continue to understand
how best to put these
combinations together,
I think we're going to use
chemotherapy less and less.
– Very interesting.
Any final words that you
want to share with anyone
who's listening today and
learning about immunotherapy
for the very first time.
– Well, you know,
some of my thoughts is that
I think we've come a long way
from, especially over the last
15, 20 years in understanding
how the immune system
interacts with ovarian cancer.
We now have better understanding.
And even though there are
no approved immunotherapies
for ovarian cancer, so yet
it's only a matter of time.
It's going to require
some form of combination.
It's important to talk to your physician
about ongoing clinical trials
and also to talk to your
physician about sequencing test,
next generation sequencing tests
in order to better understand
the nature of the cancer
and what is the best
immunotherapy approach.
I think the immune system
is the most powerful weapon
that we have in the fight
against ovarian cancer.
And we need to continue to
develop, we've made progress.
We need to continue to
study how best to use it.
And I think we're on track.
– Well, that's really wonderful to hear.
I lost my grandmother to ovarian
cancer about 30 years ago.
So it's so nice to know that
we're making so much progress.
And if there's more hope than
ever before for patients.
Once again, those watching, we're sorry,
if we didn't get to all
of your questions today,
please continue to leave them
in the Q and A we'll follow up
after today's event.
Which of course, we're also recording
this entire session will
be available to you to view
on demand next week.
So Dr. Odunsi thank you
again so much for being here
with us today, really enlightening.
– Thanks for having me.
– Dr. Odunsi thank you for sharing with us
the latest updates on
immunotherapy for ovarian cancer.
We hope we answered your questions here,
but if not Dr. Odunsi
we'll follow up on the top
and answer questions in a blog post
on the Cancer Research Institute website.
In the meantime, I
encourage you to continue
to explore the CRI resource guide.
And if you haven't
already schedule your free
confidential Clinical Trial
Navigator consultation,
thank you again, I'll be right back.
(upbeat music)

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