Advancing Precision Oncology: The Role of Targeted Therapies in HR+, HER2– Breast Cancer

The rapidly evolving field of oncology continues to advance precision medicine efforts, offering new hope for patients with complex conditions such as hormone receptor-positive (HR+), HER2-negative (HER2–) breast cancer (BC). In a recent Pharmacy Times^® Clinical Forum, Heather Moore, PharmD, BCOP, CPP, a clinical oncology pharmacist at Duke Cancer Center, moderated a discussion with pharmacists and other health care professionals from institutions such as Tampa General Hospital, Baycare, and Moffitt Cancer Center, on the latest advances in targeted therapies and the pharmacist's role in personalized cancer treatment.

Molecular model of antibody taking part in immune defense. Image Credit: catalin - stock.adobe.com

As part of the first section of the discussion, the experts discussed the treatment of HR+, HER2– BC, particularly in the context of precision oncology and the use of targeted therapies. Several drugs were discussed, including ribociclib (Kisqali; Novartis), a CDK4/6 inhibitor used in combination with aromatase inhibitors; alpelisib (Vijoice; Novartis), a PI3K inhibitor that is used in combination with endocrine therapy (ET); everolimus (Zortress; Novartis), an mTOR inhibitor that is used in combination with aromatase inhibitors; and elacestrant (Orserdu; Menarini Group), a nonsteroidal selective estrogen receptor (ER) degrader.

According to Moore, targeted therapies are designed to specifically attack cancer cells based on their unique genetic and molecular characteristics. This approach allows for more personalized treatment plans that can lead to better outcomes compared to traditional chemotherapy, which impacts both cancerous and healthy cells. Many targeted therapies have shown significant improvements in progression-free survival (PFS) and overall survival rates for patients with known biomarkers. Further, targeted therapies can help overcome resistance to standard treatments.

“I think with endocrine resistance, that's going to be a big challenge when you're looking at clinical trials or biomarkers, because you want to give as much PFS as you can,” said panelist Thomasina Morris, RPh, MHA, BCOP, an endocrine pathologist from Moffitt Cancer Center. “In the longer time frame, of course what we're trying to prevent is resistance. ...If we do combinations, or if we go back to the original treatment that we started after utilizing something else, will we still get that resistance?”

The experts stated that patients with ESR1 mutations see no additional benefits from ribociclib for maintaining therapy, but they did benefit from the drug, regardless of specific biomarkers. For alpelisib, the experts discussed including it with other therapies, but there is a potential for increased toxicity without additional benefits. However, the drug can be effectively integrated into treatment regimens for patients with PIK3CA mutations, while making sure the proper biomarkers are identified.

Additionally, effective management of adverse effects (AEs) is essential to support patient adherence to the treatment regimen. Regular monitoring of blood glucose levels and managing gastrointestinal symptoms are also important considerations for pharmacists and other health care providers when considering treatment options, according to the panelists.

Additionally, everolimus is particularly valuable for patients who have developed resistance to other therapies, such as aromatase inhibitors or CDK4/6 inhibitors, the panelists explained. It provides an alternative mechanism of action that can help control tumor growth and is often considered in the second-line setting or later, especially for patients with HR+ BC who have exhausted other options.

Lastly, the experts discuss elacestrant as a treatment option for patients who have an ESR1 mutation. They noted that this therapy is particularly relevant for those who have developed resistance to other forms of ET, and elacestrant specifically targets the ER, which is crucial in the growth of ER+ BC. The experts suggested that elacestrant is a valuable option for improving outcomes, especially for effective sequencing of therapies. Elacestrant is positioned as a potential option in the treatment landscape for patients who have already been treated with other therapies, such as CDK4/6 inhibitors.

According to the panelists, implementing targeted therapies is complex, but pharmacists can help optimize patient adherence, access to medication, manage toxicities, and collaborate with other health care providers.

“I see it as a team approach, and so it's not only just one discipline or another, and it's between the physician, the nurses, [advanced practice providers], and the pharmacy to completely work together when one hears about an issue with adherence and again, keeping them on it,” Paul Furler, PharmD, oncology clinical pharmacist at Baycare, said. “Obviously, it's mostly just for toxicity reasons—that's our opportunity to kind of give recommendations at that time if a patient is struggling with maintaining their daily dose.”

Pharmacists can also help manage AEs associated with treatments, including strategies for monitoring and adjusting doses based on patient responses. The need for individualized approaches to toxicity management can help with adherence for patients, and pharmacists should help educate and support patients about therapy. Furthermore, the experts underscored the importance of collaboration among health care providers to ensure comprehensive care for patients. Effective communication within the health care team is crucial for addressing adherence and toxicity issues.

“It's great that we have these…oral therapies before [patients] eventually have to progress to infusion treatment options,” panelist Jorge Avila, MD, a clinical pharmacist at St. Elizabeth’s Medical Center, said.