Podsada Discusses Biomarker Testing and ADC Therapies in Breast Cancer

Kimberly Podsada, MSN, NP-C

The growing availability of biomarkers has led to the advent of more targeted therapies such as the antibody-drug conjugates (ADCs) fam-trastuzumab deruxtecan-nxki (Enhertu), ado-trastuzumab emtansine (Kadcyla; T-DM1), and sacituzumab govitecan-hziy (Trodelvy). As treatments evolve, so too has the nurses’ role in understanding the nuances of sequencing and the safety and efficacy signals of each agent.

“Nurses spend a lot of time with patients and discuss what the oncologist has explained. Understanding the role of biomarkers and how that information is needed so we can make the best recommendation [is important],” Kimberly Podsada, MSN, NP-C, said. “[It is also important to] keep an open line of communication with the oncologist as well, as far as what other markers we might be testing for and staying up to date about these markers because it is a growing field. There have been a stream of new therapies and that has been exciting for us especially over the last few years in breast oncology.”

In an interview with Oncology Nursing News®, Podsada, a nurse practitioner at University of California San Diego Health in California, discussed the significance of using ADCs in an earlier line of therapy. She also highlighted how advances with oral selective estrogen receptor degraders (SERDs) are giving patients more options and how the integration of new agents is changing the treatment landscape.

How has the role of biomarker testing influenced emerging treatment considerations for patients with breast cancer?

Biomarkers have [become] more available and there are plenty of targeted therapies now because of these additional biomarkers. We are looking at biomarkers that go beyond the estrogen receptor, the progesterone receptor, and the HER2 receptor. Nowadays, we’re also looking at PD-1, PD-L1, the PIK3CA mutation, or BRCA positivity. There are many more markers now that help us to decide [on] treatments for women [in the] adjuvant and metastatic settings.

What are some agents that could challenge existing standards of care or be integrated into the treatment landscape?

In my lifetime in oncology, I have seen a couple of therapies come around that have really changed the treatment landscape, especially for HER2-positive disease. I was a part of the T-DM1 clinical trials when that came to market for the metastatic setting.

Now being a part of the DESTINY-Breast trials, the thing that has really changed the treatment landscape is the DESTINY-Breast03 [NCT03529110] information where trastuzumab deruxtecanhas now bumped T-DM1 for second line. This changes the treatment landscape, especially [in terms of] the median progression-free survival [PFS]. [The median PFS] has not been reached yet.

I am excited to see what happens now when people start using it in the second line of therapy in the metastatic setting.

We also have tucatinib [Tukysa], which is a tyrosine kinase inhibitor [TKI], for metastatic HER2-positive disease. That was an exciting clinical trial [HER2CLIMB trial (NCT02614794)] because it was the first trial that looked at patients with active brain metastases. Usually in a clinical trial, you can see stable brain metastases, but they allowed [individuals] on trial who had new, progressing, and active brain metastases. The TKI displayed a benefit in preventing new lesions from occurring and affecting what we are imagining.

How has the recent influx of approved therapies for patients with HER2-positive metastatic disease affected your practice and how are you addressing sequencing questions?

The sequencing question is always going to be out there. I look at it as we have a lot of tremendous options now for women with HER2-positive disease; T-DM1 in the adjuvant setting, trastuzumab deruxtecan in an earlier line setting for metastatic breast cancer patients, and tucatinib.

Some of it for me is based on conversations with the patient. What are their symptoms? What do they desire, as far as maybe a more oral driven therapy vs an infusion therapy? [Because of] some of the recent approvals, the sequencing will change again with trastuzumab deruxtecan now being able to be used earlier.

As far as what we now do after a second line, I [would say] move on to something like tucatinib as the following therapy, follow guidelines, and figure out the plan in collaboration with your patient because they are the one that is showing up and doing the hard work.

Can you speak to advances with novel medications, such as oral SERDs, for patients with ESR1 mutations?

This is going to be great for patients. Currently, we have an intramuscular injection, fulvestrant [Faslodex], and being able to take something by mouth instead of getting these very large injections will make patients very happy. We are seeing some promising research studies and, although it is still in clinical trials, this is another game changer.

There are always mixed thoughts about someone coming into the clinic or doing their treatment at home. [If they come into the clinic] we know they take their injections and their medicine. At the same time, that causes anxiety and stress because when [an individual] gets injections, they get anxious, and their blood pressure goes up.

If we had an oral version of it, many of us would start with the oral therapy first and I believe we are going to be seeing a couple of new oral SERDs coming to market which will be exciting and give us more options.

How are ADCs reshaping the treatment landscape for patients with TNBC?

ADCs are changing the treatment landscape for all breast cancer types. Trastuzumab deruxtecan and T-DM1, have had some of the biggest positive impacts on the breast cancer world.

In the triple-negative world, which is still an area that I want to see more research go into, it is the most challenging type of breast cancer to treat. We are continuing to come up with new methods of treating it including with ADCs.

Sacituzumab govitecan, has been approved and that is tremendous news for patients and providers to have another option for triple-negative disease. I would like to see some [approved agents] moved up into an earlier line setting—we will have to continue doing clinical trials for that.

There are [AEs] with these medications and a lot of times when some of these drugs are getting approved, they are given to people that have already been heavily pretreated. We are giving these women everything possible.

I’m also curious about what will happen to sequencing over time in the triple negative [space] when [we can start to use] any of these [agents] that are showing great efficacy and potency in an earlier line setting.We are getting there [and] we are making strides to get new therapies out there for triple-negative disease.

We are just trying to give a lot of these patients [better] quality of life as well as [improved] OS. I want women to live longer with their disease, but I also want it to be tolerable for them.