Literature
Clinical Pearls & Morning Reports
Published March 27, 2024
In this trial, did treatment with ribociclib plus a nonsteroidal aromatase inhibitor (NSAI) prolong invasive disease-free survival as compared with use of an NSAI alone?
Slamon et al. recently reported the findings of a protocol-specified interim analysis of a phase 3 trial that is evaluating adjuvant ribociclib plus endocrine therapy as compared with endocrine therapy alone in a population of patients with stage II or III hormone receptor (HR)–positive, human epidermal growth factor receptor 2 (HER2)–negative early breast cancer. Read the NEJM Original Article here.
Clinical Pearls
Q: Describe some of the features of HR–positive, HER2–negative breast cancer and its management.
A: HR-positive, HER2-negative breast cancer is the most common subtype of breast cancer, accounting for 70 to 75% of cases. The majority of cases with this subtype are diagnosed early (at stage I to III). Early breast cancer is treated with curative intent; HR-positive, HER2-negative early breast cancer is treated with surgery with or without radiotherapy or chemotherapy, followed by adjuvant endocrine therapy for 5 to 10 years. Adjuvant endocrine therapy improves outcomes in these patients; however, recurrence occurs in 27 to 37% of patients with stage II disease and in 46 to 57% of patients with stage III disease and can occur up to 20 years after diagnosis.
Q: Does the use of cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors improve survival in patients with breast cancer?
A: The results of trials in which the CDK4/6 inhibitors ribociclib, palbociclib, and abemaciclib were evaluated have shown significant improvements in progression-free survival among patients with HR-positive, HER2-negative advanced breast cancer. Ribociclib and abemaciclib have also been shown to have a significant overall survival benefit in the same patient population. Whether this benefit in advanced breast cancer extends to early breast cancer is unclear.
Morning Report Questions
Q: In this trial, did treatment with ribociclib plus a nonsteroidal aromatase inhibitor (NSAI) prolong invasive disease-free survival as compared with use of an NSAI alone?
A: A significant invasive disease–free survival benefit was seen with ribociclib plus an NSAI (letrozole or anastrozole) as compared with an NSAI alone. At 3 years, invasive disease–free survival was 90.4% with ribociclib plus an NSAI and 87.1% with an NSAI alone (hazard ratio for invasive disease, recurrence, or death, 0.75; 95% confidence interval, 0.62 to 0.91; P = 0.003). Secondary end points — distant disease–free survival and recurrence-free survival — also favored ribociclib plus an NSAI. At the time of this analysis, follow-up was ongoing, and 20% of the patients had completed the planned 3 years of ribociclib-NSAI treatment; thus, additional analyses with longer follow-up are continuing in order to fully assess the larger clinical effect of 3 years of CDK4/6 inhibition in this patient population.
Q: What was the most common adverse event of any grade in patients in the ribociclib-NSAI group?
A: The most common adverse events of any grade were neutropenia (in 62.1% of the patients in the ribociclib–NSAI group and in 4.5% of those in the NSAI group), arthralgia (in 36.5% and 42.5%, respectively), and liver-related events (in 25.4% and 10.6%). These events were also the most common events of grade 3 or higher; the most frequent event of grade 3 or higher was neutropenia, occurring in 43.8% of the patients in the ribociclib–NSAI group and in 0.8% of those in the NSAI group.