Foundation for Women's Cancer
Moderator: Dina Tizzard
04-17-15/1:00 p.m. ET
Confirmation # 1264498
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Foundation for Women's Cancer
Moderator: Dina Tizzard
April 17, 2015
1:00 p.m. ET
Operator:
This is conference #1264498
Operator:
Good afternoon. My name is (Takeshia) and I will be your conference
operator today. At this time I would like to welcome everyone to the
advanced Ovarian Cancer conference call. All lines have been placed on mute
to prevent any background noise. After the speaker’s remarks there will be a
question and answer session. If you would like to ask a question during this
time, simply press star then the number 1 on your telephone key pad. If you
would like to withdraw your question, press the pound key. Thank you, Ms.
Dina Tizzard, you may begin your conference.
Dina Tizzard:
Thank you. Good afternoon. I am Dina Tizzard with the Foundation for
Women’s Cancer in Chicago. Thank you for joining us and know that we
have a great workshop planned for you today. The goal for today’s call is to
help you understand, and learn mo about ovarian – advanced ovarian cancer
from the convenience of your home or office.
Founded by the Society of Gynecologic Oncology, the Foundation for
Women’s Cancer is a public charity dedicated to expanding public awareness,
education, research and training to improve the prevention, early detection and
optimal treatment of gynecologic cancers. The Foundation for Women’s
Cancer works diligently to make the pathway of survivorship easier and to
fund research to unlock new knowledge about ovarian and other cancers
unique to women.
Foundation for Women's Cancer
Moderator: Dina Tizzard
04-17-15/1:00 p.m. ET
Confirmation # 1264498
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We encourage to you to take a look at our website which is the
foundationforwomenscancer.org for updated content about each gynecologic
cancer. New information about cancer and the importance of nutrition, stress
and information for caregivers and much, much more. We would like to
thank (Genen tech) for their educational grant to support today’s telephone
workshop. I would also like to thank the two speakers who volunteered their
time today to share their information and answer your questions.
This is the 14th telephone workshop offered by the foundation. Today’s
Sharyn Lewin is going to begin the workshop by talking on PARP inhibitors
and recurrent ovarian cancer. Dr. John Elkas will follow and speak on
recurrent ovarian cancer, when to reoperate. As the operator said, we will
open the phone lines at around 12:45 for questions and answers and the
operator will announce that the lines are open and the presenters will do their
best to answer as many questions as possible.
Please note that they will not be able to answer specific questions regarding
your treatment. Those are best – those questions are best asked of your
managing physician. A recording of the call today will be available for replay
as of Monday, to access the recording, you may visit our website, and it will
give you the dial in and the conference ID number to be used. On behalf of
the Foundation for Women’s Cancer, we thank you for joining us today and
we hope that you find the workshop useful and informative.
The Foundation programs are only possible because of the generosity of
foundation donors. This generosity is vital if we are to continue to make
foundation programs available and at no charge. If you are interested in
making a donation, you may call the foundation headquarters at 312-5781439. You may you’re tax deductible gift to the foundation or you may log on
to our website. At this point, I would now like to turn the program over to Dr.
Sharyn Lewin.
Sharyn Lewin:
Good afternoon. For my portion of the telephone education workshop, we’d
like to speak about PAPR inhibitors particularly with recurrent ovarian cancer.
In the time that we have allotted. I’d like to talk a little bit about what PARP
inhibitors are, what they do and then to talk about some of the studies or data
Foundation for Women's Cancer
Moderator: Dina Tizzard
04-17-15/1:00 p.m. ET
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that is quite exciting as this new treatment evolves for patients, particularly
those with recurrent ovarian cancer.
So the development of PARP inhibitors as a treatment for ovarian cancer was
prompted by several observations, particularly in patients with BRCA
mutations that show an increased efficacy. So PARP inhibitors, it’s a big
word. It stands for something called Poly ADP Ribose Polymerase inhibitors,
so a very big word that we abbreviate PARP which is spelled P-A-R-P.
And PARP inhibitors have been one of the most promising avenues for
personalized treatment in ovarian cancer therapy and we’ll talk a little bit
about why that is. PARP inhibitors from what we believe their mechanisms of
action, they basically exploit something called dysregulated DNA damage
responses.
So I’m going to explain a little bit what that means, so its very important that
all women with ovarian cancer know their BRCA status. We do know over
many studies that we see a higher incidence of BRCA mutations or (BRCAy)
mutations in our women with ovarian cancer. The National Guidelines which
has now come from the Society of Gyn Oncologist or SGO from the
American Society of Clinical Oncology or ASCO and also from the NCCN
which is the National Comprehensive Cancer Network.
All of these three national organizations have recommended that all women
with epithelial ovarian cancer receive BRCA testing and the reason these
national organizations have recommended BRCA testing is that we know
approximately 17 to 20 percent of unselected ovarian cancer patients may
have a BRCA mutation and with certain cell types called (high grade)
histology. Those percentages actually maybe a little bit higher.
One of the reasons that its so important to know a woman’s BRCA status who
has ovarian cancer is of course because we want to prevent these genetic
defects from being passed on to children but we also now have some very
exciting treatment or therapeutic options and one of them is called PARP
inhibitors.
Foundation for Women's Cancer
Moderator: Dina Tizzard
04-17-15/1:00 p.m. ET
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So just to tell you a little bit about what PARP inhibitors are, and what they
do, we’ll speak about that next and then some of the data surrounding this. So
PARP inhibitors have been shown to have some exciting action in several
different solid tumors, so not only in ovarian cancer but it is also being studies
now in breast cancer, prostate cancer and pancreas cancer.
So we think that PARP inhibitors are definitely involved in DNA repair and
what’s interesting is that certain types of cancers, particularly ovarian cancer
in which there is a genetic mutation with BRCA have a defect in what’s called
homologous DNA repair and this is a pretty big word but homologous DNA
repair is an important way that the DNA in our body is actually repaired.
So DNA in some can sort of be repaired in six different mechanisms. DNA
damage happens from various different etiologies either from environmental
exposures or some type of exposure that causes injury to our genes or DNA
and when that happens it leads to either what’s called single strand breaks or
double strand breaks in the DNA itself and there are six different pathways for
this – for which this repair can be done and its sort of a very complicated
system.
But one of the ways that it is repaired is by something that’s call homologous
recombination which is a pretty big term but it is a very specific way that
double stranded DNA breaks happen and unfortunately in patients who have
BRCA mutations and then have ovarian or breast cancer for example, that
whole pathway doesn’t work properly.
So what happens is if we give a patient a PARP inhibitor and PARP is usually
responsible for DNA repair so if we give a PARP inhibitor where an
important function of DNA repair is blocked and then a patient already has
defect in for example BRCA I or BRCA II, and a whole pathway of another
repair mechanism, it – hence two repair mechanisms have basically been
altered or nonfunctional, it leads to cell death which is what we want to have
happen in cancer patients.
So its kind of a long winded explanation of the mechanism for PARP inhibitor
therapy and how we think it works particularly well in patients with BRCA
Foundation for Women's Cancer
Moderator: Dina Tizzard
04-17-15/1:00 p.m. ET
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mutations. So there have been many clinical trials and many studies looking
at various different PARP inhibitors in patients with ovarian cancer and we’ve
looked at PARP inhibitors following initial surgery and chemotherapy for
women is sort of what’s called a maintenance strategy.
So when women finish their surgery and chemotherapy, they then go on to
receive a PARP inhibitor maintenance therapy. We’ve also looked at PARP
inhibitors after a woman has had a recurrence and also after several different
lines of chemotherapy. So there are some active trials ongoing now looking at
PARP inhibitors with chemo therapy with radiation or by itself and I just want
to talk a little bit about some of the data that’s already been published and
released, as well as to talk to you a little bit about some of the ongoing studies.
So one study that was presented at our national meetings that was quite
exciting is what’s called study 19 and this is a study that was looking at
patients with ovarian cancer who received a PARP inhibitor known as a
olaparib versus placebo and this was a randomized control trial where women
were randomized to either a PARP inhibitor or a placebo which is basically a
sugar pill following completion of their upfront surgery and chemotherapy
and then looking at the data, we found that the women who had a BRCA
mutation and also who had received a PARP inhibitor had a significantly
improved what’s called progressions free survival.
So a significantly approved time before they had any evidence of cancer
recurrence. You know the study initially was not designed just to look at
women with BRCA mutations, it was really designed to look at patients who
had ovarian cancer and then received either this PARP inhibitor known as
olaparib or placebo but when we went back and looked specifically at the
response with those women and BRCA mutation, we found a very impressive
improvement in how these women did if they particularly had a BRCA
mutation and then received a PARP inhibitor.
So there was an improvement in what’s called progression free survival or
how long until there was any evidence of recurrence of almost about between
7 and 8 months. So very impressive data. There was another study
particularly looking in women with recurrent ovarian cancer that was known
Foundation for Women's Cancer
Moderator: Dina Tizzard
04-17-15/1:00 p.m. ET
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as – or is known as study 42 and this was authored by a group of researchers,
Dr. Kaufman and Dr. Domiczec and several others and was actually published
in the Journal of Clinical Oncology which is a very impressive journal.
This came out in 2014 but study 14 specifically looked at women that had
both platinum sensitive and platinum resistant disease and then looking at our
ovarian cancer patients who are in the study because the study not only looked
at ovarian cancer patients but they also looked at patients with pancreas
cancer, prostate cancer, breast cancer and other solid tumors. These were
women who were included who had several lines of chemotherapy and we
found again a very impressive response rate upon the order of approximately
34 percent in women that had platinum resistant disease as well as many prior
lines of chemotherapy.
So it’s actually very exciting data to see the response rate for a drug
particularly in women that had many prior treatments with various
chemotherapy drugs. So in this particular study, most women had at least four
prior cycles of chemotherapy regimens and are not cycled rather but four prior
regimens and the majority were also considered platinum resistant which
means that their cancer had grown while they were on carboplatin or one of
the other platinums or within six months.
So often when cancer gets to this point, it is very difficult to treat so to find in
almost 34 percent response rate was actually quite exciting to the investigators
as well as to us. So, these are two of some of the very exciting trials that has
been women with ovarian cancer who have had PARP inhibitors particularly
those with both recurrent diseases.
I should also mention there has been at least four other studies since these two
are definitely worth mentioning and in the interest of time, I’ll just talk to you
a little bit about the PARP inhibitors that were studied and some of the data
that we have. There was a study also known as Ariel 2 and some of the
preliminary data was just presented at our annual meeting of the Society of
Gyn oncologists, this meeting was just actually held in March in Chicago.
The remainder of the data is actually going to be presented in June in ASCO
but this was what’s called a phase 2 trial.
Foundation for Women's Cancer
Moderator: Dina Tizzard
04-17-15/1:00 p.m. ET
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It was a trial that was looking for efficacy or how well this particular drug
would work and this was again in patients with ovarian cancer, particularly
those who had BRCA mutations and the patients were treated with a different
kind of PARP inhibitor and again had a very impressive overall response rate
up to the order of about 65 percent based on certain CT criteria, so it was
actually very exciting data that we heard at SGO and we look forward to
hearing more information about that in ASCO.
So what’s interesting is that you know we know that a large portion of women
with ovarian cancer have BRCA mutations and the majority of studies so far
with PARP inhibitors have been in those women that have BRCA mutations
but we also know there’s a larger amount of tumors that even though patients
may not have a BRCA-I or BRCA-II mutation the tumor itself or the cancer
itself may behave that way.
So we do think there are a lot more women that may benefit from PARP
inhibitors than just those with BRACA-1 or BRCA-2 mutations and this
particular study, the Ariel-2 study that I mentioned, not only enrolls the
majority of BRCA patients but also enrolled patients that had defective
deficiencies in the tumor itself.
So, very interesting thing, an active area of study now. There’s another study
that is ongoing in Europe at this particular point which is looking not only at
BRCA mutation carriers and how their cancers respond to PARP inhibitors
but also those whose cancer tumor itself behaves sort of similarly to a BRCA
mutation and how they respond to PARP inhibitors as well too so, hopefully
once that data matures, we’ll have a lot more information that we can
hopefully offer PARP inhibitors to more women than just those who have
BRCA germ line mutations.
There are three other studies that are worth mentioning, some of you may
have heard of these studies or potentially even participated in these studies,
they’re called SOLO-1, SOLO-2, and SOLO-3. SOLO-1 is actually closed at
the present time. It was a national study and it looked at women who had
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Moderator: Dina Tizzard
04-17-15/1:00 p.m. ET
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initial chemotherapy and surgery for their ovarian cancer and then received
either a PARP inhibitor or placebo as what’s called a maintenance strategy.
So that trial has been closed. We don’t presently have the data for this but
hopefully within the next year, we will. There’s another trial called SOLO-2
which also looked at PARP inhibitors as a maintenance strategy but this time,
it was after at least two lines of chemotherapy. So a woman would have had
surgery and chemotherapy and then on went into remission and then if her
cancer recurred she might have had another line of chemotherapy and then
been eligible for the trial to be on what’s called a maintenance therapy with a
PARP inhibitor specifically olaparib.
This study is also closed too, we don’t have the results yet but hopefully
within the next 1 to 2 years that data will be matured and we will have those
results. Another study that is open now, that’s ongoing in the United States
and enrolling patients is something called SOLO-3; this is a trial looking at
patients with BRCA mutations and PARP inhibitors after two lines of
chemotherapy.
So again, a woman would have had surgery, chemotherapy, gone into
remission and then another line of chemotherapy or later and she could either
have a PARP inhibitor or some type of other systemic chemotherapy based on
her treating physician’s choice. So this is an open study now that is actively
enrolling patients and will be very interesting to see the data once the study
has accrued and has closed.
So just want to say so far, that we’ve had many studies that have been opened,
closed, some of which the data is still maturing, studies are currently ongoing.
We’ve seen a very impressive response rate in women with recurrent ovarian
cancer who particularly have BRCA mutations who have been treated with
PARP inhibitors, some of these exciting data particularly related to study 19
and study 42, that I mentioned earlier, that’s what prompted the FDA in
December to have an accelerated release of the PARP inhibitor olaparib for
women with germline mutated BRCA mutation carriers who have ovarian
cancer, what’s been FDA approved is that women need to have had at least
three prior lines of chemotherapy.
Foundation for Women's Cancer
Moderator: Dina Tizzard
04-17-15/1:00 p.m. ET
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So far we’ve seen that the side effects have been quite tolerable. Women may
experience a little bit of nausea, a little bit of fatigue and a little bit anemia but
overall the side effects that we’ve seen in the study which we can get into
more detail in the interest of time a little bit later have been quite tolerable.
So the bottom line is that you know PARP inhibitors really are one of the
most exciting areas of personalized medicine particularly for patients with
ovarian cancer when we’re thinking about all the studies and all the literature
with various different targeted agents and various different chemotherapy
agents, the data surrounding PARP inhibitors are some of the most exciting
that we seen given the very high response rates particularly in women who
have had quite a bit of chemotherapy prior.
Some of the ongoing studies now additionally are looking at PARP inhibitors
with things like Avastin or other what are called monoclonal antibodies with
different antiangiogenic drugs, VEGF receptors so I think we’re going to
continue to learn more and more about exciting combinations for PARP
inhibitors with other targeted agents and a different time points in the natural
history of ovarian cancer to see when is the best time to give this drug and if
more patients than just those with BRCA mutations can really benefit.
So I might have given quite a bit of information in the short period of time, I
think at this point I may just stress that, you know, if you haven’t had a BRCA
test, I certainly would encourage that it’s really important that all women with
ovarian cancer do receive genetic counseling and testing for BRCA mutations.
We do know such a high percentage of our women do harbor BRCA
mutations and in addition to preventing secondary cancers and of course
preventing family members from developing cancers, we now have some very
exciting treatment options or therapeutic options for women with ovarian
cancer who have BRCA mutations.
I know several studies have shown in our women with BRCA mutations a real
improvement in how women have done by using PARP inhibitors and so there
are definitely ongoing studies and more information will become available as
time goes on.
Foundation for Women's Cancer
Moderator: Dina Tizzard
04-17-15/1:00 p.m. ET
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I should say that PARP inhibitors are an oral chemotherapy drugs so they are
pills that women take by mouth. The recommended dose to start is about 400
mg twice a day. It does require taking a lot of capsules, eight capsules per
day, but it is nice to also have a break from IV chemotherapy and a little bit of
a break from such close follow-up and infusion centers and with oncologist.
So at this point, I think I’ll go ahead and conclude what I’m going to say
about PARP inhibitors. I definitely would be happy to take questions at the
end. I think I’ll go ahead and turn this over to (Dr. Elkas) to speak about
recurrent ovarian cancer as well.
Dina Tizzard:
Great. Thanks (Dr. Lewin) and now we will turn the program over to (Dr.
Elkas).
(John Elkas):
Thank you Dina and thank you (Sharyn) for a great update on PARP
inhibitors.
Today, I’m going to discuss what I think is one of the most difficult topics in
the – in the treatment of ovarian cancer, the question of when to reoperate on
any given patient and honestly in my opinion that’s one of the most difficult
questions the surgeon has ever faced with, when is the right time to offer any
patient a repeat operation. We have to balance the risks of the procedure, both
the risk of the anesthesia and the surgery itself with the potential benefits of
the operation.
When we do surgery for recurrent ovarian cancer, we try to follow the same
guidelines as we do when we operate on primary or initial surgery for ovarian
cancer. Thankfully, most patients with ovarian cancer have disease in their
abdomen and pelvis and that’s our potential candidates for repeat operations,
but who benefits from another operation is the question and unfortunately a
very, very difficult question.
While the exact criteria are unknown as who should get an operation and are
currently being studied, I think in general most GYN oncologists follow some
simple guidelines and again not every patient follow – falls into these specific
guidelines, but using these as a basis for moving ahead. I think what most
surgeons want to see before even considering a repeat operation is an
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Moderator: Dina Tizzard
04-17-15/1:00 p.m. ET
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extended progression for interval and when we talk about progression for
intervals we’re talking about date of completion of chemotherapy to the date
of diagnosis and dates of 12 months or greater are probably what we look at
when looking at significant impact in a repeat operation.
The other – The other factor that we look at often when deciding on who to
reoperate is how much disease does an individual patient have and can that
patient undergo a complete cytoreductive operation again or more simply can
we remove all the disease that exist. Again, sometimes a very, very difficult
question to answer preoperatively without actually going in and looking.
And finally I think the third measure that I use when deciding on who to
reoperate on is what is the overall performance status of the patient or in other
words for performance status what is the overall health of any given patient, is
that patient going to tolerate potentially a very big operation and the
anesthesia and the recovery period knowing that more chemotherapy is likely
to follow so all three of those factors, progression-free interval, can we
remove all of the disease and how healthy is any individual patient I think are
the three main factors that many of us use to determine who would benefit
from any specific operation.
So going into some of those factors in a little more detail, let’s talk about
progression-free interval. I talked about greater than or equal to 12 months
being a general guideline. There are some studies out there that show that
progression-free intervals of over 18 months coupled with a repeat operation
can lead to survivals numbers of over 49 months so clearly the longer the
progression-free interval, the longer time from the date of completion of
chemotherapy to the date of recurrence, the more likely that patient may
benefit from having another operation.
Predicting complete removal or cytoreduction of tumors is something that
we’ve studied for as long as I’ve been in the field and unfortunately I don’t
know that we’re much better now than we were 10 or 15 years ago. All the
CAT scans, PET scans, MRIs and such often are not entirely helpful in
determining whether or not we can completely cytoreduce or give any
significant benefit to a patient.
Foundation for Women's Cancer
Moderator: Dina Tizzard
04-17-15/1:00 p.m. ET
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I think there have been some recent proposals that prior to a repeat operation,
maybe doing a diagnostic laparoscopy, putting a little camera into people’s
belly to see if the preoperative CAT scan or PET scan was truly indicative of
what’s actually going on may make sense in some patients – in some patients.
Some of the general guidelines I think that many of us follow in deciding who
to operate on in addition to what we mentioned is looking at – looking for
patients who don’t have a lot of ascites or fluid in their belly and if there are
sites of disease evident on the CAT scan, just a few sites of disease, the fewer
the better certainly and maybe only two or three evident on CAT scan gives us
the best predictor of who may benefit.
In regards to the specifics of the surgery itself, I think we’ve made some
dramatic strides in the last decade with the advances in minimally invasive
surgery and thankfully now sometimes these secondary cytoreductive
procedures can be done laparoscopically or robotically minimizing the overall
morbidity and certainly shortening the recovery time for many patients, but
regardless of how the surgery is done, the same tenet that we follow when
doing primary cytoreduct – primary surgery – primary surgery for ovarian
cancer that all disease must be removed has to be followed.
We can’t take a patient for another operation with the thought that we’re only
going to go after half of the disease. We’re not giving maximal benefit there.
We have to be able to try to remove all disease or maybe we have to
reconsider whether the operation is of benefit in the first place.
And sometimes unfortunately that does mean a big incision and we can’t do it
robotically. Sometimes, it means we have to remove the spleen or part of the
liver or liver or even potentially do a temporary colostomy, but there’s
certainly a benefit in certain patients who we are able to completely
cytoreduce.
Thankfully, we hope to learn more in the coming years as there are actually
active ongoing studies looking at the question of secondary cytoreductive
surgery so hopefully we’ll have better guidelines in the years to come, but I
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04-17-15/1:00 p.m. ET
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want to stress that there’s often no right or wrong answer as to whether
surgery is the right next step for any given patient.
And the right answer is really the – is the decision that any individual patient
and her gynecologic oncologist make together. Thank you very much Dina.
Dina Tizzard:
Great. Thank you (Dr. Elkas) and at this point we’re going to go ahead and
have the operator open the lines for the question.
Operator:
At this time, I would like to remind everyone in order to ask a question, please
press star then the number one on your telephone keypad. We’ll pause for just
a moment to compile the Q&A roster.
Your first question comes from the line of (Owen).
(Owen):
Yes, this question is for (Dr. Lewin). Can you hear me?
(Sharyn Lewin): Yes I can.
(Owen):
OK. I’ve got three questions actually. The first question is, is olaparib ever
given or what would be the benefits of giving it with while also getting
chemo. The other questions are it’s really one question, would you
recommend maintenance when there is no evidence of disease after having
been through a regimen of chemo or do you only do the olaparib after there’s
been another recurrence after you have the three lines of chemo previously.
(Sharyn Lewin): Those are excellent questions and as you were saying this I think I actually
misspoke about one of the studies so I just want to clarify. So olaparib, which
is one type of PARP inhibitor has been studied in conjunction with
chemotherapy. There’s one, you know, particular study that’s well thought of
in this area.
We sort of found that the chemotherapy doses needed to be lowered pretty
substantially because it was too toxic to give the IV chemotherapy and the
PARP inhibitor together. You know in that particular study, we did seen
improvement in what’s called progression-free survival, which is how long
the patient live without progressing on the PARP inhibitor with chemotherapy
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as opposed to chemotherapy alone, but this - there are a lot of toxicities that
are involved so it’s just like everything else in medicine, once we start to
study something and we learn more about it there are many other questions
that arise and things we need to answer.
Right now, you know, we did seen improvement in that particular study of
giving PARP with chemotherapy, however, there were some pretty significant
toxicities that were associated with that and the doses of the chemotherapy
definitely had to be reduced so that’s kind of prompted looking PARPs more
as sort of single-agent treatment as treatment by themselves without
chemotherapy.
To answer your other question so right now PARP inhibitors are FDA
approved, you know, following three lines of chemotherapy and so, you
know, it’s kind of an interesting question. It’s sort of FDA approved as
monotherapy, which means therapy by itself specifically in women with
BRCA mutations who have had three or more lines or three or more types of
chemotherapy treatments so it’s sort of indicated to give it as treatment by
itself.
Studies looking at PARP inhibitors as a maintenance therapy have been done
and some of the data we are waiting for and, you know, as we’ve learned
more about the efficacy and how well these PARP inhibitors work we’ve
raised a lot of questions about when is the best time to give these PARP
inhibitors. You know is it as a maintenance strategy and SOLO1 I mentioned
was the trial that closed, but we don’t have that data yet, which looked at
surgery, chemotherapy and then a PARP inhibitor, olaparib as a maintenance
strategy, which means following what we think is the clinical remissions and
no evidence of cancer on CAT scans or CA 125 either giving placebo, which
is nothing, which would be the standard at this particular time versus olaparib.
So that study has closed, we just don’t have the data on that presently.
You know, other studies, which have closed are like SOLO2 for example,
which is looking at PARP inhibitors after at least two prior lines of
chemotherapy. You know, SOLO3 as I mentioned is looking at second lines
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Moderator: Dina Tizzard
04-17-15/1:00 p.m. ET
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or later and that actually is a study looking at PARPs versus physician choice
of IV chemotherapy.
In Study 19 and this is where I might have misspoken and I apologize so that
was actually a study looking at PARP inhibitors versus placebo in patients that
have had two or more prior platinum regimens and that was a study that
showed such a tremendous improvement in progression-free survival for those
patients who would have PARP inhibitors versus placebo so I hope I have
answered your question.
You know the long and short of it is that right now the only FDA approval
that we have is for olaparib, which is Lynparza, one type of PARP inhibitor as
a single-agent strategy by itself for women that have had at least three lines of
chemotherapy. Whether or not we’re going to be able to give it sooner in the
disease course and sort of use it off-label, you know, remains to be seen.
(Owen):
OK. Is that …
(Sharyn Lewin): Does that answer the questions?
(Owen):
… yes, the question is, is that currently being recommended to be given when
there’s no – as a maintenance or they have given it only after it comes back?
(Sharyn Lewin): Only after it comes back.
(Owen):
OK. Can I ask another question? I have one other.
(Sharyn Lewin): Sure.
(Owen):
How accurate is the CA 125 test given that the results of the CA 125 can
differ depending upon the lab that reads the, you know, that does the – gives
the result?
(Sharyn Lewin): In general, if the CA 125 has been elevated for a patient with ovarian cancer
in the past, it’s usually a good reliable marker and of course there are some
differences between one lab and another. There are some other things that can
cause some fluctuations in CA 125 levels, but if it was initially elevated for a
woman when she was first diagnosed for example generally it tends to be a
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04-17-15/1:00 p.m. ET
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good marker moving forward, but there are cases where that may not
necessarily be true. What do you think (Dr. Elkas)?
(Owen):
Does it always (stay) …
(John Elkas):
Yes, I know. I agree with (Sharyn) a 110 percent and I think it’s important to
stress that because of the differences in labs, we don’t use one CA 125 value.
We follow trends and that’s getting blood work every month or six weeks or
every two months to follow those trends so I don’t think any of us would
make any determination by, you know, based on any one blood test at any
particular lab.
(Owen):
OK. So but if a patient never gets down below 35, does that – that doesn’t
necessarily mean then that they have a recurrence, but when you start seeing
the CA 125 elevate and trend in that direction that would be the better
indicator, is that what I’m hearing?
(John Elkas):
I would agree.
(Sharyn Lewin): I would agree too.
(Owen):
OK. Thank you.
Operator:
And your next question comes from the line of (Michelle).
(Michelle):
Thank you for taking my call. I’m very interested in your topic. I am BRCA
– I am not BRCA positive so can you speak a little bit about the PARP
inhibitors and reoccurrence in patients who are not BRCA positive.
(Sharyn Lewin): That’s a great question. It’s something that I am actually very interested as
well too.
You know as I mentioned a large portion of women with ovarian cancer have
BRCA mutations, but an even larger percentage of the tumors or the cancers
themselves sort of behave with what we think is called like a BRCA likeness
or a B-R-C-A likeness, which means that the patient or the woman herself
does not have a BRCA mutation, but her ovarian cancer still behaves that way
and it all sort of goes back to the way that the DNA is repaired that I first
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mentioned at the beginning so we think that PARP inhibitors will help many
more women with ovarian cancer than just those with BRCA mutations, but
it’s something that’s currently being studied right now.
So there’s an ongoing trial in Europe for example looking at women who not
only have BRCA mutations, but whose tumors have BRCA mutations to see
whether or not PARP inhibitors like olaparib will have a tremendous benefit
so it’s something that’s actively being studied and we’ll have hopefully more
information about that within the next year. You know personally I do feel as
do many other GYN oncologists that PARP inhibitors can help more women
with ovarian cancer than just those with BRCA mutations.
(Michelle):
You find out if you have – if your tumor behaves BRCA-like.
(Sharyn Lewin): There are some particular companies on the market that can take tumor from
one of your prior surgeries and run different molecular tests and so they can
see whether or not these particular genes are potentially defective. You know,
this is all sort of emerging science so it’s things that still need validation to see
whether or not it matches with blood work for example and there are also
other genes not just BRCA1 or BRCA2 that are – that are active in what’s
called the homologous recombination pathway that’s where BRCA sort of fits
in and so there are other genes in that same pathway so this really may extend,
you know, beyond whether or not tumors and genes sort of behave like
BRCA1 or BRCA2 if that make sense so it all have to do with how the DNA
is really repaired on the cellular level and the cancers itself and so there are
companies that are studying this. It’s just some things that still need a little bit
more validation and further study.
(Michelle):
OK. Thank you.
Operator:
And your next question comes from the line of (Dorata).
(Dorata):
Hi. I hope my accent will be understood. I live in this country 48 years, but I
still have an accent. Anyway, I was given a choice of two trials to enter
recently. One of them is Ariel 2 that you spoke about and the other one is it’s
called SIERRA and it’s using Taxol and demcizumab.
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I am having a thought process I tend to want to do the SIERRA because at
least I know that I’m getting Taxol on a weekly basis, which is a known FDAapproved medication while the Ariel 2 only has one medication that is still in
a trial that is not yet known to help. Am I having the correct thought process
in my choice?
(Sharyn Lewin): Well it’s tough to say individually. I would – I would definitely recommend
that you speak to the physicians who are taking care of you because they
know the best details about your particular situation.
I should say in general that I really do advocate for clinical trials. This is how
we learn more about cancer and what works best for cancer and how we’ve
made so many advances for example with PARP inhibitors and some of the
data I have shared with you, but I would recommend definitely speaking to
your oncologist and they can give you a little bit more detailed information on
your current situation.
(Dorata):
I do – I do, but I don’t trust the doctors only. I feel that I need to make my
own decision also, not just trust them with the close eyes, you know.
(Sharyn Lewin): OK. Well we’re going to try to focus on general questions here that I think
will be more broadly applicable for the whole listening audience.
(Dorata):
OK. So let me just ask you did you ever hear about demcizumab, which is
new?
(Sharyn Lewin): What you say, demcizumab, I couldn’t understand.
(Dorata):
Demcizumab, d-e-m-c-i-z-u-m-a-b.
(Sharyn Lewin): (John), are you familiar with that particular trial?
(John Elkas):
I am – I’m not unfortunately.
(Sharyn Lewin): Yes. Yes.
(Dorata):
It’s done only in three places in the country, which is MD Anderson,
Oklahoma (somewhere) and (inaudible) in Philadelphia.
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(John Elkas):
I mean all three of those institutions are obviously leaders in cancer therapy,
so I don’t think you could go wrong with either trial and there’s never right or
wrong answer when going on a trial. And – and I agree with (Sharyn), I think
participation in trial is so very important …
(Sharyn Lewin): Yes.
(John Elkas):
Regardless which the one you choose.
(Sharyn Lewin): Right.
(John Elkas):
And there’s going to be risks and potential sequelae with each. I mean Taxol
obviously, (I) crippled patients with Taxol because of bad neuropathy that
they will have for the rest of their life. So whether getting – the hardest
question is always is when to treat and when to treat, when to do surgery and
when not to do surgery. And that’s what these trials are dedicated to look and
I think we just thank you for even considering, you know, going on a trial.
(Dorata):
Yes, I already made a decision that I will go to the SIERRA, the demcizumab
and Taxol.
(Sharyn Lewin): That sounds like a good decision. I agree, don’t think you can go wrong, I
really don’t, that much (inaudible).
(Dorata):
Especially that I’m BRCA negative, so I’m not sure how much help I will get
from – they will (operate), so I’m going to try the demcizumab and Taxol.
It’s a monoclonal antibody, so we’ll see what happens.
(Sharyn Lewin): That makes very good sense, that must be similar to Avastin, some type of
monoclonal antibody.
(Dorata):
Probably, yes, probably similar but Avastin didn’t help me much. So, I hope
it’s not exactly like Avastin.
(Sharyn Lewin): I think you’ll be in good hands. Those are some of the leaders in our field at
those institutions, so.
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(Dorata):
Yes, I belong to (10) and actually I was approved already by OncoMed, their
pharmaceutical. So, they know that I’ve (got) Avastin before and they still
approved me, so who knows
(Sharyn Lewin): OK.
(Dorata):
You understand what I’m saying?
(John Elkas):
Yes ma’am and we thank you for you call and for willingness to participate,
so maybe we can take the next question.
(Dorata):
OK, thank you.
(John Elkas):
Thank you ma’am.
Operator:
And your next question comes from (Rick).
(Rick):
Yes, for other doctor, could you please just comment in general on what you
expect as far as side effects with PARP inhibitors?
(Sharyn Lewin): Absolutely, we do have, you know, published data from the various different
studies that I mentioned on particular side effects. As you may know from
treatment with any chemotherapy and of course we do talk about a lot of the
common reaction that happened but overall these things are not as common.
There can be some – a little bit of nausea. These are oral pills. By and large,
there is a little bit of fatigue. Things that are not that uncommon to other
types of chemotherapy. We do have – seen a little bit of GI issues, a little bit
of nausea, a little bit of diarrhea and some anemia lowering up the blood temp
as well too. Those are the major ones.
(Rick):
Thank you.
Operator:
And your next question comes from the line of (Carolyn).
(Carolyn):
My question is – I think I already have the answer. I was asking if Avastin
was a PARP inhibitor but from your questions I see that it isn’t.
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(John Elkas):
You’re correct ma’am.
(Sharyn Lewin): You’re correct. Avastin is what’s called an antiangiogenic inhibitor works on
blood vessel, so it’s a little different mechanism of action.
(Carolyn):
Well, is it ever described as a maintenance medication?
(John Elkas):
Possibly in certain circumstances.
(Sharyn Lewin): Correct.
(Carolyn):
All right, thank you very much.
(Sharyn Lewin): You’re welcome, thank you.
Operator:
And your next question comes from the line of (Nancy).
(Nancy):
Yes, hello, I guess my question is when you’re on a PARP and it is a
effective, does that mean that the tumors are getting reduced or do they
disappear for whatever that period of (months) is and how long can you be on
a PARP inhibitor?
(Sharyn Lewin): So, yes, it does mean that the tumors shrink. They can even disappear, so we
measure response either based on CA-125 levels if that’s a good marker for a
patient or with CAT scans to measure the size of different tumors, to see how
it’s responding. So, yes to your first question. You know, right – on our other
chemotherapy drug women are also on PARP inhibitors until we find
evidence that it’s not working very well. So, you could be on it for or a
woman could be on it for a very long time as long as she’s not having any
toxicities or, you know, adverse side effects and as long as it’s working.
(Nancy):
Thank you very much.
(Sharyn Lewin): You’re welcome.
Operator:
And your next question comes from the line of (Amy).
Next question comes from the line of (Sharon).
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(Sharon):
Yes, you mentioned there’s been (no) radiation, my third treatment after a
recurrence. First occurrence was five years and then I had reoccurrence and I
had the same chemotherapy regimen which (inaudible) me for about a year.
The second occurrence, they have to get a new 17 radiation treatments and I
haven’t heard any mention of radiation which I understand does not cure, it
just shrinks the size of the tumor.
(John Elkas):
Well, you know, ma’am you asked a very intriguing question and there are
certainly some places around the world where radiation is still a hallmark in
therapy for ovarian cancer. I think in this country and many of parts of
Europe, we will use radiation sometimes like we use surgery, (even though)
the recurrence setting as evidently was the case with you. If there’s a
localized tumor in the liver or spleen or somewhere where the radiation
doctors feel that he could adequately treat the tumor, then radiation in replace
of surgery sometimes is the fantastic answer and has the potential to not only
shrink the tumor but potentially eradicate it.
Obviously, every individual circumstance is different but you’re bringing up a
case – you’re bringing up another treatment and all of the things that we’re
talking about today, the radiation, the PARP inhibitors, I think it just goes to
cement the fact that, you know, the treatment for ovarian cancer thankfully is
rapidly changing and that advances are just around the corner. Some of which
we already have at our – at our fingertips and I think the future is bright.
(Sharon):
Well, that’s very encouraging. Each time I’d been told it’s contained, so
there’s my GYN oncologist (inaudible) smile (inaudible) that a (set) of that is
contained. So, I just keep hoping it will stay contained.
(John Elkas):
Well you obviously have a very good doctor.
(Sharon):
Oh, I have a wonderful doctor. I don’t know if you want his name but I’m in
– he’s Indianapolis and I feel like he’s been my lifesaver so far. So I felt good
that, you know, I know this can reoccur again and when that recurs the second
time, it was against my lower bowel which caused perforation and now I’m
having (inaudible) iliostomy but I’ve learned to do that and I can – I can live
with that if they can keep the cancer away.
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(John Elkas):
You know, you bring up an excellent point. I think that – I think we try to
explain this to patients every day that, you know, our diabetic patients live
with insulin or asthmatic patients live with their inhalers and our ovarian
cancer patients live with chemotherapy and the key word is live and move on
and your testament, we thank you.
(Sharon):
I am, I am, life is good and thank you for all your research and for your
workshop today.
(Sharyn Lewin): Thank you for sharing your story too.
(Sharon):
Yes.
Operator:
And your next question comes from the line of (Karen).
(Karen):
I guess that’s me. I do have a question about the – I guess my sister has
ovarian cancer stage IV and she tested positive for the BRIP1 gene but not the
BRCA gene. So, she is going on the PARP inhibitor. They allowed her to go
on and hopefully next week and I just want to see if you have seen any
research with that particular gene in the PARP inhibitors?
(John Elkas):
I haven’t. (Sharyn), have you?
(Sharyn Lewin): I haven’t either. You know, there are a lot of women are now having panel
testing, so women with ovarian cancer having BRC1 and BRC2 testing and if
that’s normal or negative, then going on to receive a panel testing to look at
other genes, so maybe that’s how she was she diagnosed with a BRIP1
mutation. There are other genes in this pathway for DNA repair, the
homologous recombination pathway that I mentioned.
So, that’s very intriguing, it makes sense if the insurance will pay for the
PARP inhibitors, even though she doesn’t have a BRCA mutation, that’s
wonderful because it would be very interesting to see and hopefully will help
her.
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(Karen):
Yes, that what’s we’re hoping too but I guess somewhere I did read that the –
that gene, that they did do a study but you don’t know of that study with that –
with that gene, particular gene?
(Sharyn Lewin): It’s possible, I just don’t know that data if there is a study looking at that.
(Karen):
OK, OK. Yes, and I guess she went to the Dana-Farber Center in Boston and
I guess that’s where they (recommend) 23 additional panel genes versus, you
know, when she tested negative for the (inaudible).
Operator:
And your next question comes from the line of (Gwen).
(Gwen):
Yes, I was wondering, you know, you’ve spoken of (olaparib) but I know that
there’s been other PARP inhibitors out there, can you speak to any of the
efficacy or any of the efficacy of some of the other PARP inhibitors?
(Sharyn Lewin): I’m sorry, would you mind repeating that question one more time?
(Gwen):
OK, you know, the (olaparib) we know just got approved but there’s other
PARP inhibitors that are out there, what do we know about it, their efficacy in
ovarian cancer?
(Sharyn Lewin): OK, great question, so you know Lynparza –Lynparza or olaparib is the only
FDA-approved PARP inhibitor at this time other than the PARP inhibitor that
was just approved with the Ariel 2 study. So, the other PARPs are still being
studied to be honest. So we only know, you know, about the ones that have
been FDA-approved or the ones that are being utilized on study.
Operator:
And your next question comes from the line of (Mary).
(Mary):
My question is that there are certain types of tumors, certain types of testing
that requires a certain amount of tumor and certain vaccine studies that
requires certain amount of tumor, is there any time that is actually a
disadvantage to have surgery for recurrence too soon when you have such a
small amount of tumor, that molecular testing or some of these other study
trials would no longer be an option.
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(John Elkas):
You know, it’s a great question and actually we have a vaccine trial here that
we’re doing locally. You know, thankfully there are other ways outside of
surgery to get tissue. Our radiology colleagues can now many times get
enough tissue for molecular staining not for necessarily vaccine studies,
depending on how much tissue is actually needed but often enough tissue for
some molecular analysis.
To take a patient to the operating room carries with it obviously a lot of
inherent risks, especially in patients with ovarian cancer who have often
undergone very large, initial surgeries or taking them back to the operating
may mean even for a small tissue biopsy, may mean another very big
operation. And doing that just to get tissue for a potential future study, I don’t
necessarily know the risks and benefits equate there. Did I answer that
question?
(Mary):
Yes, yes, you did and a short followup question is to what type of scan and
frequency of scanning is really ideal to give you the best information you need
as to an operable recurrence that had scans or CT scans?
(John Elkas):
For me personally, I would prefer a PET scan – I would prefer a CAT scan. I
think a PET scan help us in many ways identifying sites of disease but to let
me know surgically is the tumor too close to the pancreas, is it too close to the
aorta? That information of PET scan often just can’t help us with. So for
surgical planning, I think most of us use a CAT scan for that, not that we don’t
use PET scans, we use PET scans quite frequently but not necessarily
specifically for surgical planning.
And again, sometimes if we’re uncertain as to whether we’re going to go
ahead and do a very big operation. Sometimes we’ll put a little camera in, do
a laparoscopy before we commit to a big operation and the long recovery
period. And sometimes we can get the information we need with just a
laparoscopy but unfortunately that’s not always the case.
(Mary):
Thank you, that’s very helpful information.
(John Elkas):
Thank you.
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Operator:
And your next question comes from the line of (Crede).
(Crede):
Hi, thank you for taking my call. This is for Dr. (Lewin), you were talking
about the platinum- resistant study, I think it was number 42, is that study still
open?
(Sharyn Lewin): No, that study has actually closed. It was analyzed and written up, so we do
have the results.
(Crede):
OK, thank you. And second question, you’re recommending that people get
BRCA tested, where I would do that, will I go to a center like Moffitt in
Tampa for example?
(Sharyn Lewin): Absolutely, yes, so there’s various different avenues to obtain BRCA testing.
Some GYN oncologists like me are testing my own patients in the office or
you could see a genetic counselor as well. So, I would definitely speak to
your oncologist then and ask where’s the best resources for obtaining the
genetic counseling and testing. But yes, the Moffitt should absolutely have
resources available for you there to do that.
(Crede):
Thank you.
Operator:
And your next question comes from the line of (Amy).
(Amy):
Hi, I wanted to know how large a tumor on a reoccurrence needs to be, to be
operated on, specifically is it a danger to the patient like my CA-125 initially
was 1600 when I have stage IV and then four and a half years later, my CA125 it took six months to go from 4 to 17 but I did have a small tumor in the
abdomen. And the question is, if I’m going to have the operation and then
have to have the chemotherapy afterwards, why don’t we just try – (can we
ever) try chemotherapy or – anyway, so I’m getting carried away here.
(John Elkas):
No, no, you’re actually asking a very, very thoughtful question and there’s not
a right or wrong answer to that. And that’s why we are uncertain as to
whether reoperations make any difference and our hope in the future is that
we never will need to reoperate on a patient and our PARP inhibitors and be
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that as it may will be all that we’ll need. (May you) benefit from an
operation? You may.
I can’t tell you one way or another. You may want to speak to your GYN
oncologist about a laparoscopy with such a small tumor, possibly with
minimally invasive technique robotically or laparoscopically, you know you
can be assessed that way but if for any reason you don’t feel comfortable or
you’re not well enough for an operation, commencing chemotherapy without
surgery is a very, very viable option.
(Amy):
And did they get rid of the tumor that chemotherapy if it’s small?
(John Elkas):
Absolutely.
(Amy):
OK, all right. So next time I think if there’s a next time I will try that because
my CA-125 is extremely reliable and I don’t want another huge surgery but I
also heard before in the past that a patient that is a reoccurrence patient, this
question (does) make sense to me but why don’t – why would a surgeon wait
until you’re symptomatic if you have a tumor, don’t they want to get it before
it gets too big and is there any way to tell if the tumor is going to get really big
or how fast it’s going to grow?
(John Elkas):
You know, another great question for which I don’t necessarily know that I
have a great answer. Does it make sense to remove a smaller tumor versus a
larger tumor? Absolutely it makes all the intuitive sense in a world. I wish to
say that we had studies in the recurrence setting that it made a difference.
I hope some day we will and hopefully some day with a (occurring) GOG
study we will have that data but sometimes trying chemotherapy, sparing the
big operation prior to proceeding with surgery maybe the better option and
only operating if indeed the tumor does become symptomatic. So, there’s not
a great answer unfortunately. The right answer is what and your GYN
oncologist come up with.
(Amy):
Right, yes, well I did switch doctors after the second big operation because I
was in the hospital for 12 days and it was such a small tumor, I thought, you
know, this isn’t for me but the second doctor did say that he would do a
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laparoscopy but – anyway hopefully there won’t be another time. And also, I
don’t know, you did mention neuropathy and I just want to know Taxotere is
the same thing as Taxol only it doesn’t as much neuropathy, is that correct?
(Sharyn Lewin): Pretty much, yes. There has been studies looking and the two drugs are very
similar in terms of how they work but the side effects are different. So, yes,
Taxotere/ docetaxel had much less risk of neuropathy. Other side effects that
the Taxol doesn’t have but there – most in studies have shown to be pretty
equivalent in terms of how they work.
(Amy):
All right, thank you both so very, very much. I really appreciate the – your
conference.
(John Elkas):
Thank you.
(Sharyn Lewin): Thank you.
(Amy):
Good bye.
Dina Tizzard:
I think at this point we’re going to go ahead and wrap up our conference as
we’ve gone overtime a little bit. So, I would just like to thank again both, Dr.
(Lewin) and Dr. (Elkas) for sharing all their wonderful information with us
and the Foundation for Women’s Cancer thank you for joining us today.
And again, you will be able to have access to a replay via our Web site or also
a transcript will be posted on our Web site. So once again, thank you
everyone for joining us and thank you Doctors (Lewin) and (Elkas).
(John Elkas):
Thank you.
(Sharyn Lewin): Thank you both.
Dina Tizzard:
All right, thank you.
Operator:
This concludes today's conference call. You may now disconnect.
END