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No significant survival benefits were found when comparing three CDK4/6 inhibitor combinations with initial treatment for HR-positive, HER2-negative metastatic breast cancer.
Real-world data compared treatment with three CDK4/6 inhibitors in HR-positive, HER2-negative metastatic breast cancer.
When comparing three CDK4/6 inhibitor combinations during the initial treatment for hormone receptor (HR)-positive, HER2-negative metastatic (spreading) breast cancer, no significant overall survival (OS) advantage was found, as presented during the 2024 San Antonio Breast Cancer Symposium (SABCS).
“To date, we have no head-to-head phase 3 studies comparing the CDK4/6 inhibitors,” noted Dr. Kari B. Wisinski, professor of medicine at the University of Wisconsin Carbone Cancer Center in Madison, Wisconsin, in a presentation of the data.
The median follow-up was 33 months for the Ibrance (palbociclib) plus an aromatase inhibitor (AI; 6,831 patients) group, 16 months for the Kisqali (ribociclib) plus AI (1,279 patients) group and 21 months for the Verzenio (abemaciclib) plus AI (1,036 patients) group.
Overall survival (OS): time from diagnosis or treatment start until death from any cause.
Progression-free survival (PFS): time during which the disease does not worsen.
Neutropenia: low levels of neutrophils, a type of white blood cell.
Thrombocytopenia: low levels of platelets in the blood, which may cause easy bruising or bleeding.
Primary end point: the main objective measured at the end of the study to see if treatment worked.
Real-world data was used from a retrospective study analyzing 9,146 patients from 280 US sites. The study investigators compared OS rates between treatment groups.
The median OS before an unadjusted analysis in the Ibrance plus AI group was 54.4 months, 60.3 months in the Kisqali plus AI group and not reached (NR) in the Verzenio plus AI group. When an OS is not reached, it means not enough patients in the respective group died at the time of data collection. The OS rates in the Ibrance plus AI group at 12, 24 and 30 months were 89.6%, 77.4% and 71.4%, respectively. For the Kisqali plus AI group, these OS rates were 90%, 78% and 73.3%. In the Verzenio plus AI group, the OS rates were at 12, 24 and 30 months were 88.4%, 76.1% and 71.5%.
After applying the adjusted analysis, the median OS for the Ibrance plus AI group was 54.6, 59 months for the Kisqali plus AI group and 64.5 months for the Verzenio plus AI group. The OS rates at 12, 24 and 30 months for the Ibrance plus AI group were 89.7%, 77.5% and 71.4%, respectively. These were 89.2%, 77.3% and 72.2% for the Kisqali plus AI group, respectively. For the Verzenio plus AI group, the OS rates were 88.2%, 76.1% and 71.5%, respectively.
Also in the adjusted analysis, 3,714 deaths were reported across all three groups: 3,096 in the Ibrance plus AI group (45.3%), 328 in the Kisqali plus AI group (25.6%) and 290 in the Verzenio plus AI group (28%). The median follow-up duration in group 1 was 33 months, 15.7 months in the Kisqali plus AI group and 21.5 months in the Verzenio plus AI group.
Regarding side effects, there were higher rates of neutropenia in the Ibrance plus AI group (67%) than the Kisqali plus AI group (60%) and the Verzenio plus AI group (21.9%). However, anemia was greater in the Ibrance plus AI group (5.4%) and the Verzenio plus AI group (6%) versus the Kisqali plus AI group (0.9%). Thrombocytopenia was consistent across the three groups: 1.6% for the Ibrance plus AI group, 0.9% for the Kisqali plus AI group and 1.9% for the Verzenio plus AI group.
“Now there are some limitations for this analysis. The [Ibrance plus AI] and [Verzenio plus AI] cohorts had smaller numbers and shorter follow-ups, and the point estimates were relatively (or possibly) unstable after 30 months. In addition, as always with real-world analysis, there is potential for unmeasured confounders,” Wisinski noted.
Wisinski applied these real-world data to the following phase 3 trials: PALOMA-2, MONALEESA-2, MONALEESA-3, MONALEESA-7 and MONARCH-3.
The primary end point for each study was progression-free survival (PFS), and all three demonstrated benefit, Wisinski explained. When comparing the median OS, Wisinski stated that “median OS has been improved with the addition of [Kisqali], [Verzenio] demonstrated a clinical meaningful benefit but it was not statistically significant, and [Ibrance] did not provide benefit.” In the real-world analysis the median OS rates were quite consistent with what was observed in these studies, Wisinski added.
Patients included in the trial had HR-positive, HER2-negative metastatic breast cancer, were 18 years or older and started index treatment with either Ibrance plus AI, Kisqali plus AI or Verzenio plus AI.
“The P-VERIFY study suggests that there is no difference in OS among first-line CDK4/6 inhibitors and this would align with the PFS data that we have from those first-line studies,” Wisinski concluded. “However, the statistically OS beneficent that we have seen as only been with [Kisqali]. I think that longer follow-up would be very valuable and although real-world analyses have limitations it is unlikely that we will have a head-to-head study, and thus, these data add to the information that we have.”
“Comparative Overall Survival of CDK4/6 Inhibitors Plus an Aromatase Inhibitor (AI) in HR+/HER2– MBC in the US Real-World Setting.” By Dr. Hope S. Rugo, et al. Presented at the San Antonio Breast Cancer Symposium, San Antonio, Abstract PS2-03.
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