medwireNews: Supplementing endocrine therapy (ET) with ribociclib significantly decreases the relapse risk in people with hormone receptor-positive, HER2-negative, early breast cancer, indicate phase 3 data.
The NATALEE trial met its primary endpoint, “demonstrating a statistically significant and clinically meaningful improvement” in invasive disease-free survival (iDFS) with the addition of the CDK4/6 inhibitor, investigator Dennis Slamon (David Geffen School of Medicine at UCLA, Los Angeles, California, USA) told delegates of the 2023 ASCO Annual Meeting in Chicago, Illinois, USA.
He added that these findings “support ribociclib and nonsteroidal aromatase inhibitors as a new treatment of choice in a broad population – broader than we’ve seen before – of patients with stage II and stage III disease.”
The research team recruited 5101 men or pre- or postmenopausal women with stage IIA (either N0 with additional genetic risk factors or N1), stage IIB, or stage III early breast cancer and randomly assigned them to receive letrozole or anastrozole for at least 5 years either with or without ribociclib 400 mg/day given on a 3 weeks on, 1 week off schedule for up to 3 years. Men and premenopausal women additionally underwent ovarian suppression with goserelin.
Noting that in adjuvant trials of the other CDK4/6 inhibitors abemaciclib and palbociclib, the drugs were administered for up to 2 years, Slamon explained that the 3-year duration was chosen for NATALEE as an extended duration “is crucial to prolong cell cycle arrest and drive more tumor cells into irreversible senescence.”
He reported the results of the second interim analysis, conducted at a median follow-up of 27.7 months, in which the 3-year iDFS rates were 90.4% in the ribociclib plus ET group and 87.1% in the ET alone group.
This equated to an absolute benefit of 3.3 percentage points and a significant hazard ratio (HR) for recurrence or death of 0.748 in favor of the combination.
Add-on ribociclib was also associated with a significant improvement in distant DFS, at a 3-year rate of 90.8% versus 88.6% with ET alone, giving an absolute benefit of 2.2 percentage points and an HR for distant disease or death of 0.739.
The overall survival data are “still relatively immature” and additional follow-up is planned, but there is a trend in the right direction, with an HR for death of 0.759 in favor of ribociclib, albeit without reaching statistical significance at this point, said the presenter.
Moving onto the safety data, Slamon highlighted that “no new side effects or safety signals” were seen with the 400 mg dose.
With regard to adverse events (AEs) of special interest, neutropenia of at least grade 3 occurred in 43.8% of ribociclib-treated patients and 0.8% of those given ET alone, while the rates of liver-related AEs and QT interval prolongation of this severity were 8.3% versus 1.5% and 1.0% versus 0.5%, respectively.
The most common any-grade AEs leading to treatment discontinuation in the ribociclib arm were liver-related AEs and arthralgia, in 8.9% and 1.3%, respectively. The corresponding rates of discontinuation due to these AEs in the control arm were 0.1% and 1.9%.
Nadia Harbeck, from LMU University Hospital in Germany, who discussed the presentation, noted that patients with “[h]igh-risk gene expression test results constitute an unmet medical need” and congratulated the NATALEE authors on including these patients in the trial.
She added that the results are “good news for our patients,” as now there are two CDK4/6 inhibitors – ribociclib and abemaciclib – “that increase the chances for cure in this setting, both with an acceptable safety profile.”
The discussant stressed, however, that further research is needed into “optimal therapy management to allow patients to complete the intended therapy duration” and to identify individuals who remain at risk despite adjuvant therapy, as well as to define new therapeutic options for these patients.
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