TNBC Awareness Day: Practice-Changing Treatments Grow Clinicians Confidence in Helping Patients

Triple-negative breast cancer (TNBC) is a challenging disease for patients, but new practice-changing treatments shouldn’t just give clinicians confidence in treating their patients, but confidence for the patients to expect better outcomes.

In an interview with Targeted Oncology^TM, Miguel Pelayo, MD, a physician partner with Florida Cancer Specialists & Research Institute, discusses these therapies and how they inspire confidence in him when treating patients with TNBC.

Pelayo discusses trials such as the KEYNOTE-522 study (NCT03036488), which looked at patients treated with neoadjuvant pembrolizumab (Keytruda), and how that has changed the early treatment setting for this patient population.¹

He also looks at later lines of treatment in the ASCENT trial (NCT02574455) for patients with metastatic TNBC with sacituzumab govitecan (Trodelvy), and how the DESTINY-Breast03 trial (NCT03529110) investigating trastuzumab deruxtecan (Enhertu) have changed his view of certain patients with HER2-low breast cancer similar to patients with TNBC.^2,3

These trials have inspired new confidence in the treatment of patients with TNBC—a confidence that Pelayo hopes can be conveyed to patients by their physicians.

How has the field of treatment for patients with TNBC changed in the past few years?

It has changed drastically; we have had an explosion of trials in the last 2 years in the different settings of [TNBC]. I think of it in 3 primary areas: the neoadjuvant setting before surgery, adjuvant setting after surgery, and the metastatic setting. In the last few years, we've had practice-changing studies that give patients better options and a better chance of success, which leads to a bright future of how we're going to be helping people.

Of the recent trials, what has helped to change the field the most?

In the neoadjuvant setting, we incorporate immunotherapy to our treatments now. We use primarily chemotherapy before surgery and we did pretty good; we had a pathologic complete response [pCR] of approximately 50% with our standard chemotherapy, but [the KEYNOTE-522 study] incorporated pembrolizumab with standard chemotherapy, which saw that number I just gave increased by a factor of about 14 percentage points [to 65%].1 We were attaining more pCRs, which is important for a patient's chance for success with cancer recurrences and overall survival [OS]. The interesting thing [was that] regardless of their PD-L1 status, everyone benefited.

We tend to think in certain cancers about a success only being seen in patients who express sensitivity to immunotherapy through PD-L1 status, tumor mutation burden, and other factors we check. So, that study was interesting in how it showed all patients benefited, regardless of their PD-L1 status. The OS on that study was not statistically significant, but it was improved. So, I think it's a matter of waiting for the data to mature, and possibly we will see that.

What have been the treatment targets in TNBC that are instrumental to moving the field forward?

[The issue with targets in] TNBC is the lack of targets. We have a PiK3-kinase for all of breast cancer, including triple negative, and I think with the DESTINY trials of HER2-low [disease] using trastuzumab deruxtecan, [it showed] how effective that is in those patients. Some patients with TNBC have a HER2 immunohistochemistry at 1+ or 2+, which is technically considered triple negative but technically also HER2 low. That study was interesting in that it was compared against physicians’ choice chemotherapy, and essentially, trastuzumab deruxtecan doubled the progression-free survival and increased OS compared with standard chemotherapy, which changed the way I thought of things.

We typically thought of HER2 as a black and white situation, but now we know they're shades of gray and that is practice changing. The study that was shown did not have [many patients with TNBC] present, but in our practices, we know how many patients we already have with HER2 1+ or HER2 2+ disease, and [patients with] 2+ would have to have a fluorescence in situ hybridization-negative [result] to truly be considered HER2-low. I think that was an interesting trial, and now I'm looking back at my patients to see if they have that.

What are some challenges in the TNBC field that still need to be addressed?

There's a lot of challenges in that when we have a study show us some positive signs, we will always want to reach for more. I mentioned the KEYNOTE-522 trial, and the pCR rate was 65% [in that trial].1 What about the other people that didn't get pCR, what do we do for them? We don't have an answer for that. We have data on patients who did not receive immunotherapy, so we have standard chemotherapy as the new adjuvant therapy. We have a trial called the Create-X trial that took those patients after neoadjuvant chemotherapy and treated them with capecitabine.⁴

We have data of an improved OS in that study, but we don't have that information as far as what to do regarding a patient who is being treated with neoadjuvant immunotherapy. The other thought is, we are using these medications for all patients—would patients with lesser disease with a lesser stage require less treatment, and still have the same result? When we have good studies that come out, it raises good questions and I think that's where we're at. Hopefully each year we are making steps in the right direction, but in TNBC, the lack of targets is always going to be a challenge.

With these changes, do you feel more confident in treating your patients with TNBC?

Absolutely. A good example of that is a year ago, we had a new antibody-drug conjugate sacituzumab compared against standard chemotherapy, which we’ve been using for years, and it showed incredible results.² That was the ASCENT trial, and it was interesting how it dramatically increased response rates compared with [treatments] that I was confident in using before and now I have this new medication that works so much better.

The key is confidence in telling patients that we have better options. We have options which are causing more responses and increasing survival with manageable [adverse events] that we are very comfortable taking care of. That's what I want to communicate to patients, is confidence—confidence that we have good medicines, and not only that, but having these good therapies and giving patients more time leads to better therapies. That confidence is something I'm hope I'm transferring into my patients.

What is some advice you might give community oncologists treating patients with TNBC?

In the community, I think it's important to have a good relationship with your colleagues in the sense of other specialties. We realize the importance of neoadjuvant treatment in TNBC, and having that knowledge imparted to the colleagues you work with for cancer treatment…can offer these patients more chances of success. Since we all work as a team, we all have different tools to help the patient, but that understanding of maybe stopping before taking someone to surgery and having an opinion by a medical oncologist to see if the patient would benefit from therapy before surgery is so important.

Another thing that's important is never to forget about genetic testing. TNBC is a reason to test for genetics because we know of an association with a germline BRCA1 mutation, and that knowledge is important to make sure we don't get too caught up in starting a treatment, because that also has treatment implications for patients.

^References:

^{1. Schmid P, Cortes J, Pusztai L, et al; KEYNOTE-522 Investigators. Pembrolizumab for early triple-negative breast cancer. N Engl J Med. 2020 Feb 27;382(9):810-821. doi:10.1056/NEJMoa1910549}

^{2. Bardia A, Hurvitz SA, Tolaney SM, et al; ASCENT Clinical Trial Investigators. Sacituzumab govitecan in metastatic triple-negative breast cancer. N Engl J Med. 2021 Apr 22;384(16):1529-1541. doi:10.1056/NEJMoa2028485}

^{3. Trastuzumab deruxtecan data impresses at ESMO. Cancer Discov. 2021 Nov;11(11):2664-2665. doi:10.1158/2159-8290.CD-NB2021-0382}

^{4. Masuda N, Lee SJ, Ohtani S, et al. Adjuvant capecitabine for breast Cancer after preoperative chemotherapy. N Engl J Med. 2017;376(22):2147–2159. doi: 10.1056/NEJMoa1612645}