Results of RIGHT Choice phase 2 clinical trial show Kisqali doubled PFS and showed fewer adverse events.
Ribociclib (Kisqali; Novartis) plus endocrine therapy (ET) produced a nearly 1-year progression-free survival (PFS) benefit compared with combination chemotherapy in the first-line treatment of pre- and perimenopausal patients with aggressive forms of hormone receptor-positive, human epidermal growth factor receptor-2 negative (HR-positive/HER2-negative) metastatic breast cancer (MBC), including in patients with visceral crisis, according to results from the phase 2 RIGHT Choice (NCT03839823) trial presented at the San Antonio Breast Cancer Symposium in Texas on December 6, 2022.1
“These findings suggest that, through the use of first-line ribociclib plus endocrine therapy, we may be able to avoid or delay chemotherapy and spare patients, even those with aggressive, life-threatening disease, the toxicities and discontinuations associated with chemotherapy,” Yen-Shen Lu, MD, PhD, a professor at the National Taiwan University Hospital, said in a statement.1
Patients whose breast tumors express the estrogen receptor (ER) and/or the progesterone receptor and do not overexpress the growth factor receptor HER2 often receive a CDK4/6 inhibitor, such as ribociclib, plus a form of ET, which blocks the tumor-promoting effects of estrogen, as a first-line treatment. However, some physicians treat aggressive tumors, such as those with visceral crisis, with chemotherapy.1
The study comprised 222 premenopausal or perimenopausal patients with HR-positive/HER2-negative aggressive breast cancer, more than half of whom had visceral crisis. Of these, 112 were randomly assigned to receive ribociclib plus an aromatase inhibitor (anastrozole or letrozole) and goserelin, which decreases ovarian estrogen production. Investigators assigned the other 110 study participants to receive a physicians’ choice combination chemotherapy regimen.1
Patients treated with ribociclib plus ET had a PFS of 24 months, nearly 1 year more than that of those treated with chemotherapy, at 12.3 months. The median time to treatment failure was also longer among patients treated with ribociclib plus ET: 18.6 months compared with 8.5 months among those treated with chemotherapy.1
The overall response rate was similar between the 2 treatment arms, at 65.2% for ribociclib plus ET and 60% for chemotherapy. However, serious, treatment-related adverse events (TRAEs), such as diarrhea and fatigue, were seen in 1.8% of patients receiving ribociclib plus ET and in 8% of those receiving combination chemotherapy. In addition, 7.1% of patients treated with ribociclib plus ET and 23% treated with chemotherapy discontinued at least 1 part of the study treatment, because of TRAEs.1
Lu said he hopes that forthcoming subgroup analyses will show clinical characteristics that may help physicians predict which patients will respond best to ribociclib plus ET compared with those who respond better to chemotherapy.1
The press conference’s moderator SABCS co-director Virginia Kaklamani, MD, who is a professor of medicine in the division of hematology/oncology at UT Health San Antonio and the leader of the breast cancer program at UT Health San Antonio MD Anderson Cancer Center, said it is the first time ribociclib plus endocrine therapy has been compared to chemotherapy.2
“This will change some of the standards of care,” she said.2
Nevertheless, “a lot of doctors hesitate, because they believe that combination therapy can provide a higher response rate,” Lu said at the press conference.2
Limitations of this study include its small sample size as a phase 2 trial, as well as the findings relating only to first-line treatment.1
“Results should be interpreted with caution until further study can be done,” Lu said, when he presented his abstract later in the day.3
1. First-line ribociclib plus endocrine therapy may be more effective than combination chemotherapy in patients with aggressive breast cancer. American Association for Cancer Research. News release. December 6, 2022. Accessed December 6, 2022. https://www.aacr.org/about-the-aacr/newsroom/news-releases/first-line-ribociclib-plus-endocrine-therapy-may-be-more-effective-than-combination-chemotherapy-in-patients-with-aggressive-breast-cancer/
2. Press conference I. San Antonio Breast Cancer Symposium. December 6, 2022.
3. Lu Y-S. Primary results from the randomized phase II RIGHT Choice trial of premenopausal patients with aggressive HR+/HER2- advanced breast cancer treated with ribociclib + endocrine therapy vs physician’s choice combination chemotherapy. Presented at: San Antonio Breast Cancer Symposium; Henry B. Gonzalez Convention Center in Texas: December 6, 2022.