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The investigational cyclin-dependent kinase (CDK) 4/6 inhibitor dalpiciclib could be a new treatment option for patients with HR-positive/HER2-negative advanced breast cancer, according to results from the .

In the phase III study, use of the drug in combination with fulvestrant achieved a progression-free survival (PFS) benefit of 8.5 months compared with fulvestrant alone, reported Binghe Xu, MD, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College in Beijing.

"These findings support and fulvestrant as a new treatment option in patients with HR-positive/HER2-negative advanced breast cancer who relapsed or progressed on prior endocrine therapy," Xu said in a presentation at the American Society of Clinical Oncology (ASCO) virtual meeting.

Also at the ASCO session, investigators updated overall survival (OS) data from the phase III and trials, showing that palbociclib and ribociclib, respectively, have each maintained prolonged survival benefits in patients with HR-positive/HER2-negative advanced breast cancer.

Commenting on results from the three trials, Otto Metzger, MD, of Dana Farber Cancer Institute in Boston, stated that "Fulvestrant plus a CDK4/6 inhibitor is clearly the treatment of choice for patients experiencing disease progression on frontline endocrine therapy."

DAWNA-1

Xu explained that dalpiciclib as a monotherapy has demonstrated tolerability and preliminary antitumor activity in heavily pretreated patients with HR-positive/HER2-negative advanced breast cancer. The objective of DAWNA-1 was to evaluate the drug in combination with fulvestrant in patients who have relapsed or progressed on previous endocrine therapy.

The trial included 361 patients randomized 2:1 to receive dalpiciclib plus fulvestrant or placebo. Xu and colleagues found that at a median follow-up of 10.5 months, patients randomized to receive dalpiciclib plus fulvestrant achieved a PFS of 15.7 months versus 7.2 months for fulvestrant alone, and a 58% reduced likelihood of disease recurrence or death (HR 0.42, 95% CI 0.31-0.58).

"Generally, PFS in all pre-specified subgroups favored dalpiciclib-fulvestrant and showed a hazard ratio of less than one, regardless of menopausal status, presence of visceral metastases, or previous lines of endocrine therapy," Xu reported.

OS data were not mature with a total of 25 deaths documented.

The median duration of exposure was 9.4 months with dalpiciclib and 9.9 months with fulvestrant in the dalpiciclib plus fulvestrant group, and was 6.1 months with fulvestrant in the placebo group.

Dalpiciclib plus fulvestrant demonstrated a tolerable safety profile, Xu said. The prevalence of grade ≥3 adverse events (AEs) was higher in the dalpiciclib group, with 82% of patients having grade 3 or 4 neutropenia, and 62% developing neutropenia, while no patient in the placebo group had these AEs.

However, the number of AEs leading to treatment discontinuation or death were comparable between the two groups, Xu said.

PALOMA-3 and MONALEESA-3

Massimo Cristofanilli, MD, of Northwestern University in Chicago, and PALOMA-3 investigators continued to observe an improvement in OS with palbociclib after a median follow-up of 73.3 months, with an updated median OS in the palbociclib plus fulvestrant arm of 34.8 months versus 28.0 months in the placebo arm (HR 0.81, 95% CI 0.65-0.99). The 5-year OS rate was 23.3% in the palbociclib arm and 16.8% in the placebo arm.

In updated results from MONALEESA-3, Dennis Slamon, MD, PhD, of the University of California Los Angeles, reported that the "previously demonstrated robust and clinically meaningful OS benefit with ribociclib and fulvestrant compared with placebo plus fulvestrant was maintained after almost 5 years of follow-up in post-menopausal patients with HR-positive/HER2-negative advanced breast cancer."

Specifically, at a follow-up of 56.3 months, median OS for patients taking ribociclib in combination with fulvestrant was 53.7 months versus 41.5 months for fulvestrant alone (HR 0.73, 95% CI 0.59-0.90). Investigators also reported prolonged OS in the first-line (median OS not reached vs 51.8 months) and second-line (39.7 vs 33.7 months).

"I think that the good news for clinicians is that we have more that one choice," said Metzger. "These drugs were not compared head-to-head in clinical trials, but based on the data from individual studies we know that these individual CKD 4/6 inhibitors are very efficacious."