Ongoing Trial Examines Current Breast Cancer Treatment

SystHERs, an ongoing study, is providing insight into current treatment patterns, long-term survival and patient experience with a variety of treatments for HER2- positive metastatic breast cancer (MBC). Mohammad Jahanzeb, M.D., medical director of Sylvester Comprehensive Cancer Center and professor of medicine at University of Miami Miller School of Medicine, discussed the trail at the 2017 Miami Breast Cancer Conference.

Jahanzeb spoke about SystHERs results with respect to de novo and recurrent cancer, CNS metastases, and outcomes by hormone receptor (HR) status. He also discussed future directions of the registry trial. The first patient was enrolled in 2012 and the study will continue into 2020, looking at both initial and follow-up care. SystHERs is examining treatment patterns and outcomes in nearly 1,000 patients enrolled from 100 sites in the United States.

The primary objectives are progression-free survival (PFS) and overall survival (OS). The secondary outcomes include examining comparative effectiveness and safety of current HER2-targeted regimens, and evaluating the effect of patient characteristics and sequencing on PFS and OS.

A precursor to this study was registHER, which also evaluated patients with HER2-positive MBC. This study ended follow-up in 2009, creating a space for SystHERs to continue. SystHERs researchers have said that therapy options for HER2-positive MBC have changed dramatically and real-world data are needed on the natural history, treatment patterns, and outcomes for these second- and third-generation anti-HER2 therapies.

Jahanzeb focused on the lessons learned from this registry study so far, particularly that patients with low HR-positive disease had poorer OS compared with those with HR-positive, making them less likely to receive hormone therapy. Patients with low HR-positive disease are similar to the HR-negative subgroup in regard to OS. In comparison with the HR-negative subgroup, patients with HR-positive disease had a higher percentage of recurrent metastatic disease at 53.6 percent.

In a finding from a comparison study of registHER to SystHERs, the proportion of patients with de novo disease within the metastatic population was higher, most likely due to the use of advanced screening techniques that allow metastases to be detected more accurately, as well as a reduction in recurrences related to the availability of HER2-targeted adjuvant therapy.

What is the current landscape of HER2-positive breast cancer?

Further research is needed to determine the benefits of hormonal therapy in patients with HER2-positive MBC with low HR expression, Jahanzeb said in an interview about his presentation at the conference.The demographics of patients with metastatic HER2-positive breast cancer have changed. Now, about 70 percent of these patients are estrogen receptor (ER)-positive, rather than 50 percent in the past. The use of adjuvant Herceptin (trastuzumab) selectively cures ER-negative patients, but ER-positive patients not much. About 9 percent have CNS metastasis at presentation. But their survival is longer than what’s been reported in the literature because of improvement in therapies, and possibly due to stage migration.

What is important to know about SystHERs?

Patients who have weak positivity for estrogen receptors, from 1 percent to 10 percent, are not as appropriate for hormonal therapy as [patients with] stronger positivity.It is about a 1,000-patient registry [drawing patient data] from 100 centers all over the United States in various settings such as small to large private practices, hospital-based groups, and academic medical centers. It enrolled HER2-positive patients that have been diagnosed within six months of their entry into the registry and could have received any therapy in the course of their illness even it if was on research. Even though it is a Genentech-sponsored registry, enrollment was not restricted to patients receiving Genentech’s products.

What specific factors were being recorded?

SystHERs started in an era when we were already giving Herceptin routinely in the adjuvant setting, so the ratio of ER-positive versus ER-negative in the SystHERs registry is 70 percent ER-positive and 30 percent ER-negative, which means ER-positive patients are relatively resistant to the chemotherapy plus Herceptin approach, and they are more likely to relapse than the ER-negative patients, who are more likely to be cured. And that’s what makes a case for giving such patients an extra year of neratinib, which is consistent with the ExteNET trial results that ER-positive patients tend to benefit, but not the ER-negative subgroup.What the practices were recording was very basic; is the patient still alive? Is the patient still responding? What was the first-line treatment? What was the second-line treatment? What was the third-line treatment? Did they lose their hair or not? It was all observational.

What do you think are important takeaways from SystHERs?

The agents that were used were anti-HER2 compounds such as Herceptin, Perjeta (pertuzumab), Kadcyla (T-DM1), Tykerb (lapatinib), chemotherapy and hormonal therapy. Also, a small use of other anti-HER2 compounds with or without experimental therapy was observed.First and foremost, it establishes the feasibility of capturing variable experiences from these registries that are very important, that we should perhaps not just take clinical trial data as generalizable without confirming that whatever outcomes we saw can be reproduced in the real-world patients, who are not being treated in a research setting.

Is there anything else you'd like to highlight about this presentation?

It also shows that it is feasible to collect patient-related outcomes with an observational registry, which can inform the design of future trials.It appears that survival for these patients who have access to modern anti-HER2 therapies has improved greatly, despite the inherently poor prognostic nature of HER2-positive disease.