Tailoring Second-Line Treatments for HR-Positive, HER2-Negative Metastatic Breast Cancer

Tailoring Second-Line Treatments for HR-Positive, HER2-Negative Metastatic Breast Cancer

The dynamic landscape of second-line treatments for patients with HR-positive, HER2-negative metastatic breast cancer presents both opportunities and challenges for oncology nurses and APPs, highlighting the importance of staying informed about the latest advancements, understanding the limitations of current therapies, and proactively managing patient care.

During a Community Case Forum event focused on second-line treatment for HR-positive, HER2-negative metastatic breast cancer, Melissa Rikal, FNP-BC, AOCNP, nurse practitioner at Sarah Cannon Research Institute Oncology Partners in Nashville, Tennessee, discussed recent advancements in the space and ongoing challenges to address. The conversation highlighted significant developments in therapeutic options, the importance of personalized treatment plans, and the evolving role of molecular testing.

Advancements in Endocrine and Targeted Therapies

Rikal noted that since the FDA approval of the partial estrogen receptor agonist tamoxifen (Soltamox) in 1977, the treatment landscape has significantly evolved. This started with introduction of aromatase inhibitors in 1995, particularly anastrozole (Arimidex) and letrozole (Femara), which block the conversion of testosterone to estrogen to reduce estrogen levels in the body. This was followed by selective estrogen receptor degraders (SERDs) like fulvestrant (Faslodex), an injectable SERD, in 2002 and more targeted therapies such as everolimus in 2012.

The development of CDK4/6 inhibitors, starting with palbociclib (Ibrance) in 2015, revolutionized treatment options in the last decade. These have included drugs like ribociclib (Kisqali) and abemaciclib (Verzenio). These drugs inhibit the cyclin-dependent kinases 4 and 6, which are crucial for cell division, thus slowing cancer progression. There were also PI3K inhibitors that entered the space like alpelisib (Piqray) in 2019, followed by the first oral SERD, elacestrant (Orserdu), in 2023 and the AKT inhibitor capivasertib (Truqap). “So [there are] lots of good, different, and targeted therapies for these patients now,” Rikal said.

Tailoring Treatment Plans for Each Patient

With all of these available options to treat patients with HR-positive, HER2-negative metastatic breast cancer, it becomes essential for teams to tailor treatment plans to individual patients, considering factors like previous therapies, side effect profiles, and patient preferences. For instance, ribociclib in combination with aromatase inhibitors is often chosen for its efficacy and manageable side effects. However, for patients who experience severe side effects, alternatives like abemaciclib, which has a different toxicity profile, may be preferable​.

Another critical aspect of personalized care is the use of molecular testing to guide therapy decisions. The detection of ESR1 mutations, which can confer resistance to aromatase inhibitors, is particularly important. Liquid biopsy techniques are commonly used to identify these mutations and inform the choice of subsequent therapies​.

"ASCO and NCCN guidelines … essentially agree that we should be testing these patients at each time of progression for the ESR1 mutation, and they both agree that we should be using liquid biopsy," Rikal said. “ASCO guidelines give a little bit of leniency with tissue biopsy, but [both guidelines] say not to use archival tissue, like from their initial diagnosis, because it’s not going to capture it well.”

Challenges and Future Directions

Despite these advancements, several challenges remain. One issue is the side effect profiles of endocrine therapies, which can impact patient adherence and quality of life. For example, aromatase inhibitors are associated with significant joint pain and hot flashes, while tamoxifen carries risks of deep vein thrombosis and endometrial cancer.

Additionally, the pharmacokinetics of fulvestrant can be problematic, as achieving steady-state levels can be difficult, potentially leading to incomplete estrogen receptor degradation. This limitation highlights the need for continued research into more effective and convenient SERDs​.

Non-adherence to endocrine therapy is another significant issue due to toxicity, with approximately 49% of patients remaining adherent to their full 5-year course.