FDA approval of a new drug regimen helps reduce risks

BYLINE: Denise Heady

Newswise — Teri Boudreaux is a two-time breast cancer survivor and is grateful for the time she gets to spend with her family, whether it’s traveling with her husband, playing with her grandchildren, hiking, relaxing on the beach or exploring new hobbies like pickleball.

But through all of this, there remains a constant fear in the back of her mind: the possibility that the cancer will come back.

“I think the biggest fear for many of us survivors is breast cancer recurrence,” Boudreaux said. “It's a lifelong worry.”

Boudreaux was first diagnosed with triple-negative breast cancer in 1990, when she was just 38 years old. After treatment, she was cancer-free for nearly two decades.

Then in 2017, she was tested for the BRCA gene and the result was positive. At the same time, during a self-examination, she noticed a lump in her breast and it turned out to be early hormone receptor (HR)-positive/HER2-negative breast cancer.

This type of breast cancer is the most common subtype of the disease, accounting for nearly 70% of all breast cancer cases in the United States.

Endocrine therapy is currently used to block or reduce estrogen production so that cancer cells cannot grow and spread. However, there is still a risk that the cancer will return years after the initial diagnosis. In stage 2 patients, the risk of recurrence is 27 to 37 percent, and in stage 3 patients, the risk is 46 to 57 percent.

Boudreaux was diagnosed with stage 2 of the disease and was not happy with her progress.

“I didn't want to look on the Internet because every time I did, everything I read scared me,” Boudreaux said.

When her neighbor, who had undergone breast cancer treatment several years earlier, recommended that she visit the UCLA Health Santa Clarita Cancer Care Center, she made an appointment with oncologist Dr. Rena Callahan in the hope of getting some answers.

The start of the NATALEE clinical trial

While discussing her options, Dr. Callahan, an associate professor of clinical medicine at the David Geffen School of Medicine at UCLA and an investigator at the UCLA Health Jonsson Comprehensive Cancer Center, suggested that Boudreaux participate in a clinical trial studying the benefit of adding the targeted therapy drug ribociclib to conventional hormone therapy for the adjuvant treatment of HR-positive, HER2-negative early-stage breast cancer.

“Endocrine therapy alone has saved countless lives, yet some patients still experience relapse of stage 4 disease,” said Dr. Callahan. “These relapses are both devastating and often life-limiting. While ribociclib was already known to prolong survival in advanced cases, its potential to prevent relapse in early-stage breast cancer offers hope for curing many more patients.”

Ribociclib is a cyclin-dependent kinase inhibitor that blocks the activity of cyclin-dependent kinase 4/6 enzymes that promote cell division and cancer growth.

In the early 2000s, a team of researchers led by oncologist Dennis Slamon, MD, PhD, chair of hematology-oncology at the David Geffen School of Medicine at UCLA and director of clinical and translational research at the UCLA Health Jonsson Comprehensive Cancer Center, led the discovery program that found cyclin-dependent kinase inhibitors to be effective in treating HR-positive breast cancer. Their work ultimately helped lead to the U.S. Food and Drug Administration (FDA) approving ribociclib and other related drugs for the treatment of advanced, metastatic breast cancer.

Building on this earlier research, the team launched an international clinical trial called NATALEE, studying ribociclib in women with early-stage disease.

Boudreaux was one of more than 5,000 women who enrolled.

“I felt like this was a good opportunity to hopefully prevent recurrence and help other women,” Boudreaux said.

Participants were randomly assigned to receive either ribociclib plus endocrine therapy consisting of a nonsteroidal aromatase inhibitor or endocrine therapy alone.

The median duration of study follow-up was 34 months, with 20% and 57% of patients receiving three years and two years of ribociclib treatment, respectively.

Promising results lead to FDA approval

The results of the study, published in March 2024 in the New England Journal of Medicine, showed that adding ribociclib to endocrine therapy significantly increased the time a person with HR-positive, HER2-negative early stage breast cancer at stage 2 or 3 lives without the cancer coming back.

“We found that adding ribociclib to standard hormone therapy resulted in a relative reduction in the relapse rate of up to 25%,” said Dr. Slamon, the study's lead author and principal investigator. “And that's huge for this patient group, which makes up the majority of breast cancer cases.”

The study's secondary endpoints, distant disease-free survival and relapse-free survival, also favored treatment with ribociclib and endocrine therapy. Distant disease-free survival rates were 90.8% for the combination group, compared with 88.6% for endocrine therapy alone. Patients with the combination had a relapse-free survival of 91.7%, compared with 88.6% for endocrine therapy alone.

Side effects were similar in both groups. The most common problems were neutropenia, arthralgia and liver-related events.

These findings ultimately led the FDA to approve ribociclib in combination with hormone therapy for the adjuvant treatment of HR-positive, HER2-negative early-stage breast cancer. The approval was granted on September 17.

“These results are changing the way we screen and treat patients,” said Dr. Slamon. “This is a new option we can now offer patients to further minimize their risk of cancer recurrence.”

Move forward

Boudreaux participated in the treatment group of the clinical trial and it has now been three years since her treatment.

“I didn't really have any side effects and honestly didn't have any problems during the clinical trial,” Boudreaux said. “I feel really good and I'm looking forward to spending more time with my family and grandchildren.”

The former nurse continues to be cared for by Dr. Callahan, but has relaxed a bit since the study began. And now she's looking forward to traveling and staying active with her retired husband.

“We love cruising and traveling to Europe,” Boudreaux said. “And we just discovered pickleball, which is a new addiction. We play almost every day.”