The investigational cyclin-dependent kinase (CDK) 4/6 inhibitor dalpiciclib might be a new treatment alternative for patients with HR-positive/HER2-negative advanced breast cancer, based on results from the DAWNA-1 trial.
In the phase III study, use of the medication together with fulvestrant attained a progression-free survival (PFS) benefit of 8.5 months as well as 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 dalpiciclib 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 in the ASCO session, researchers updated overall survival (OS) data from the phase III PALOMA-3 and MONALEESA-3 trials, demonstrating that palbociclib and ribociclib, respectively, have each maintained prolonged survival advantages in patients with HR-positive/HER2-negative advanced breast cancer.
Commenting on outcomes from the 3 trials, Otto Metzger, MD, of Dana Farber Cancer Institute in Boston, said that”Fulvestrant plus a CDK4/6 inhibitor is clearly the treatment of choice for patients experiencing disease progression on frontline endocrine therapy.”
Xu clarified that dalpiciclib for a monotherapy has shown tolerability and preliminary antitumor activity in heavily pretreated patients with HR-positive/HER2-negative advanced breast cancer. The aim of DAWNA-1 was to evaluate the drug in combination with fulvestrant in patients who have relapsed or improved on previous endocrine therapy.
The trial included 361 patients randomized 2:1 to get dalpiciclib and fulvestrant or placebo. Xu and colleagues discovered that at a median followup of 10.5 months, patients randomized to receive dalpiciclib plus fulvestrant achieved a PFS of 15.7 months versus 7.2 weeks for fulvestrant alone, and a 58% decreased likelihood of disease recurrence or death (HR 0. 42, 95percent 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 weren’t older using a total of 25 deaths recorded.
The median length of exposure was 9.4 weeks with dalpiciclib and 9.9 months with fulvestrant in the dalpiciclib and fulvestrant group, and was 6.1 months with fulvestrant in the placebo group.
Dalpiciclib and fulvestrant revealed a tolerable safety profile, Xu said. The prevalence of regular ≥3 adverse events (AEs) was greater in the dalpiciclib group, with 82% of patients having grade 3 or 4 neutropenia, and 62% growing neutropenia, whereas no patient in the placebo group had these AEs.
However, the number of AEs leading to treatment discontinuation or death were comparable between both groups, Xu said.
PALOMA-3 and MONALEESA-3
Massimo Cristofanilli, MD, of Northwestern University at Chicago, and PALOMA-3 investigators continued to observe an improvement in OS with palbociclib after a median followup of 73.3 months, using an upgraded median OS in the palb