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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 rate us and review us on Apple Podcast.