Emergence of Encouraging Biomarkers in TNBC Provide Potential for Personalized Care

Debra Patt, MD

The emergence of antibody-drug conjugates, immunotherapy, and PARP inhibitors have moved the needle forward in the treatment of patients with triple-negative breast cancer (TNBC), according to Debra Patt, MD, and the investigation of emerging biomarkers in the disease may provide further opportunities for personalized care.

“Several encouraging biomarkers are under investigation in TNBC. For example, I’m very interested in the potential role of the androgen receptor. Understanding how we can potentially use androgen receptors as a therapeutic target could be quite meaningful in the future,” said Patt. “Many other targets are under investigation. We must ensure that we are accruing patients to these clinical trials. We need answers faster so that we can give the right therapy to the patients who need them most.”

In an interview with OncLive^® during the 2020 Institutional Perspectives in Cancer webinar on Breast Cancer, Patt, ​a breast medical oncologist and the vice president of Texas Oncology, highlight​ed recent advancements and novel approaches in TNBC.

OncLive^®:What impact has the approval of sacituzumab govitecan-hziy (Trodelvy) had on patients with TNBC?

Patt: It's an incredibly important drug for patients with TNBC. The survival among patients with metastatic disease continues to be limited, and we need new therapeutic opportunities. This agent provides patients with a great option, that is unlike any other agent that we've been able to administer in the past. We must carefully manage the toxicity, but we're very excited about offering this option to our patients.

Which patients with TNBC can receive sacituzumab govitecan?

Currently, all patients with TNBC can receive sacituzumab govitecan; this is unlike other therapies in the breast cancer paradigm, such as immunotherapy that can only be administered to a specific subset of patients.

Over time, as we develop more targeted therapies for TNBC, we will have a better understanding on which patients will derive the most benefit from sacituzumab govitecan.

However, as of now, this therapy has a broader application.

As demonstrated in the phase 3 IMpassion130 trial, the combination of atezolizumab (Tecentriq) and nab-paclitaxel (Abraxane) led to a clinically meaningful OS benefit in treatment-naïve patients with locally advanced or metastatic TNBC with PD-L1 expression. Could you expand on this regimen?

The combination of atezolizumab and nab-paclitaxel has been an incredible addition for patients who express PD-L1 and have TNBC. Many patients have had long responses, and there appears to be an OS benefit. I’m excited about the other areas that we may be able to use this therapy in, such as the frontline setting, that have not yet received FDA approval.

This combination tends to be used in the frontline setting because it is well tolerated. Otherwise, patients in this space typically receive a single agent.

Immunotherapy combinations are also under evaluation in the early-stage setting. What have been some of the most compelling datasets to date?

At Texas Oncology, we helped accrue patients to the KEYNOTE-522 trial, which evaluated the addition of pembrolizumab (Keytruda) to chemotherapy in patients with T2 or node-positive TNBC who were treated in the neoadjuvant setting.

In this study, we saw an augmentation of pathologic complete response in patients who received pembrolizumab vs those who received placebo. This was really exciting. TNBC is a terrible disease, so anything that we can do to improve the outcomes of these patients, with minimal toxicities, is going to be very meaningful.

An FDA approval [for this combination] is being pursued; however, due to the current environment in 2020, this has been a challenge. Looking forward, I'm excited about immunotherapy potentially moving into an earlier setting, in the neoadjuvant treatment of patients with TNBC, where we need to be most aggressive.

PARP inhibitors have also been added to the TNBC arsenal. Could you expand on the benefit of these agents?

PARP inhibitors also bring value to the table in this setting. To date, 2 PARP inhibitors have received regulatory approval: olaparib [Lynparza] and talazoparib [Talzenna]. Both agents have demonstrated meaningful clinical end points. At our center, we participated in a trial that evaluated talazoparib in the neoadjuvant setting; we were very excited about that trial, but it was discontinued.

Several questions remain regarding PARP inhibition. Which drug should we use? How exactly should we use it? We must address these questions in a way that is not toxic. But these are incredibly meaningful drugs that can control a disease that would otherwise be a challenge for a long period of time. In my opinion, we need to develop more targeted therapies for these patients so that we can extend their progression-free survival and overall survival.

You mentioned that androgen receptor targeting is an area of interest. Are any ongoing research efforts examining this potential biomarker?

Ongoing studies are looking at already FDA-approved medications for prostate cancer in breast cancer, but they remain pretty limited. I continue to watch these efforts with great interest.

Clinical trials are needed to further evaluate emerging biomarkers in the space. Does a stigma surrounding these trials still exist?

For some people, there will always be a perception that patients who enroll to these trials are ‘guinea pigs.’ We must heighten awareness on the importance of these trials because this is how we discover novel agents. Clinical trials are a standard in the field of oncology and are important to health education, as well as health literacy.

Could you spotlight the growing role of quality of life and patient-reported outcomes in ongoing clinical trials?

Knowing that you're following toxicity closely and managing any adverse effects that a patient may experience in a more calculated and systematic way, is an advantage for patients. I believe that PROs are of escalating importance.

Notably, we are currently participating in a rollout of an electronic PROs tool across statewide practice to try to use in all patients on therapy for that very reason. Ensuring that you are capturing the patient's story as optimally as you can, which is always an advantage in clinical trials, is really beneficial.