Jul 18, 2019
Welcome to the ASCO Daily News podcast. I'm Lauren Davis. And joining me today is Dr. Priya Rastogi, who specializes in the diagnosis, treatment, and prevention of breast cancer at the Magee-Womens Hospital of the University of Pittsburgh Medical Center. And she's also the senior associate medical director for the NSABP Foundation.
Today, we're discussing the topic of recurrence among patients with
HER2 positive breast cancer, progress and providing more aggressive
therapies in early breast cancer for those patients whose cancer is
more likely to recur. Namely those with residual invasive disease
following taxane and trastuzumab based treatment given before
surgery is our area of focus. Dr. Rastogi, welcome to the
podcast.
Hi, Lauren, happy to discuss the exciting results from the
KATHERINE study.
We're glad you're here. So as an investigator of the KATHERINE
study, I'd like to hear a little bit about some of the findings. So
I understand that the study showed that T-DM1 reduced the risk of
disease recurring by half compared with trastuzumab in HER2
positive early breast cancer.
Yes. So in terms of background information, patients with HER2
positive early breast cancer receiving neoadjuvant treatment had
favorable outcomes if they achieve a pathological complete
response. But patients with residual breast cancer in the surgical
specimen have a higher risk of recurrence. And so that's some of
the rationale of how the KATHERINE study was set up.
The KATHERINE trial was an open label study with 1,486 patients
with HER2 positive early stage breast cancer who received
neoadjuvant chemotherapy plus HER2 targeted therapy that included a
taxane and trastuzumab followed by surgery. And then all these
patients had residual invasive disease in the breast and/or
actually in lymph nodes. So within 12 weeks of surgery, patients
were assigned to either T-DM1 or to trastuzumab.
And as you mentioned, the primary endpoint was IDFS. And so in the
KATHERINE study, T-DM1 significantly reduced the risk of developing
an invasive disease free survival event by three years by 50%. And
this corresponds to an absolute improvement in three year invasive
disease free survival of 11 percentage points. So this is really
exciting.
So the invasive disease free survival rate was 77% with
trastuzumab, and it increased to 88.3% with T-DM1. So the KATHERINE
trial demonstrates that neoadjuvant therapy can be used to identify
patients at increased risk for recurrence based on less than
optimal response to standard neoadjuvant therapies who can then
benefit by switching to T-DM1. The overall survival analysis has
not yet matured. We had a total of 98 deaths, 56 deaths with
trastuzumab and 42 with T-DM1 for a hazard rate of 0.7. So clearly,
this study will need more follow up.
So the FDA approved T-DM1 as adjuvant treatment for this patient
population. Do patients have immediate access?
Yes, so this is also exciting news that the US FDA approved T-DM1
for the adjuvant treatment in patients with HER2 positive early
stage breast cancer with residual invasive disease after
neoadjuvant taxane trastuzumab based therapy. The results and
approval form the foundation of a new standard of care in patients
in this setting. And this should lead to access and availability
for patients. Patients should discuss with their physicians and
their insurance providers.
That's exciting. So one of the things we always think about are
side effects. What should specialists tell their patients?
Yeah, so as you mentioned, side effects are very important. So the
safety profile of T-DM1 is as expected from what has been seen in
the metastatic setting in the use of T-DM1. The main adverse events
in our study was a decrease in platelet counts, an increase in
sensory neuropathy and liver enzymes compared to trastuzumab.
Although, these side effects are mostly mild. Fatigue and nausea
were also greater. But they were manageable and reversible. So the
side effect profile is similar to what had been seen in the
metastatic setting and the efficacy is fantastic for this drug.
Oh, that's great. Were there any surprises in the results?
So the analysis by the subgroups demonstrated that there was a
benefit across all the key subgroups. So for example, patients with
operable or inoperable cancers at presentation, hormone receptor
positive or hormone receptor negative, post neoadjuvant positive or
negative nodes, and even patients with very small residual disease
all had a tremendous benefit from T-DM1. So this is also very
exciting that all the subgroups benefited.
So what do you think is on the horizon for breast cancer
studies?
That is also a very important question. So immunotherapy is a type
of cancer treatment which also helps the immune system fight
cancer. And immunotherapy has been approved in other cancers. One
type of these drugs is atezolizumab, which belongs to a class of
drugs known as the checkpoint inhibitors. By inhibiting the
checkpoint proteins such as PD-L1 and PD-1, these drugs enhance the
ability for the immune cells to attack cancer cells.
So recently, the FDA approved atezolizumab in combination with
chemotherapy for the initial treatment of women for advanced triple
negative breast cancer with PD-L1 positive tumors. So the NSABP
Foundation in collaboration with the German Breast Group is
conducting a phase III study, it's NSABP B59 [INAUDIBLE], for
patients with early stage high risk triple negative breast cancer.
And so this trial is evaluating neoadjuvant chemotherapy with
atezolizumab or a placebo followed by surgery. Patients then
receive an additional six months of either atezo or placebo after
surgery. And the co-primary end points are pathological complete
response and event free survival. And this study will address if
neoadjuvant atezolizumab in combination with neoadjuvant
chemotherapy followed by adjuvant atezolizumab will improve
outcomes in this high risk patient population.
That's fantastic. It sounds like there's a lot of things to look
forward to. Again, today, my guest has been Dr. Rastogi. Thank you
so much for being on our podcast today.
It has been a privilege. And thank you for inviting me to talk
about the KATHERINE study.
And to our listeners, thank you for tuning in to the ASCO Daily
News podcast. If you're enjoying the content, we encourage you to
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