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. 2024 Feb 7;14(1):3129.
doi: 10.1038/s41598-024-53151-8.

Comparative overall survival of CDK4/6 inhibitors in combination with endocrine therapy in advanced breast cancer

Coralea Kappel  1 , Mitchell J Elliott  1 , Vikaash Kumar  1 , Michelle B Nadler  1 , Alexandra Desnoyers  2 , Eitan Amir  3   4
Affiliations

Comparative overall survival of CDK4/6 inhibitors in combination with endocrine therapy in advanced breast cancer

Coralea Kappel et al. Sci Rep. .

Abstract

Individual trials of abemaciclib, palbociclib, and ribociclib show a similar impact on progression-free survival yet differing statistical significance for overall survival (OS). A robust comparative evaluation of OS, safety, and tolerability of the three drugs is warranted. A systematic literature search identified phase 3 randomized clinical trials reporting OS of CDK4/6 inhibitors (CDK4/6i) in combination with endocrine therapy in ER-positive/HER2-negative advanced breast cancer. Trial-level data on OS and common and serious adverse events (AE) were extracted for each drug. In the absence of direct comparisons, a network meta-analysis was performed to evaluate pairwise comparative efficacy, safety, and tolerability of each of the CDK4/6i. Seven studies comprising of 4415 patients met the inclusion criteria. Median follow-up was 73.3 months (range: 48.7-97.2 months). There were no statistically significant differences in OS between any of the CDK4/6i. Compared to palbociclib, ribociclib and abemaciclib both showed significantly higher GI toxicity (grade 1-2 vomiting OR 1.87 [95% CI 1.37-2.56] and OR 2.27 [95% CI 1.59-3.23] respectively). Compared to palbociclib, abemaciclib was associated with more grade 3-4 diarrhea OR 118.06 [95% CI 7.28-1915.32]. In contrast, palbociclib was associated with significantly more neutropenia than ribociclib and abemaciclib but significantly lower risk of grade 3-4 infections. Abemaciclib had significantly less grade 3-4 transaminitis and grade 3-4 neutropenia than ribociclib. Treatment discontinuation and death due to AE were significantly higher with abemaciclib than palbociclib and ribociclib. There is no statistically significant difference in OS between CDK4/6i despite differing statistical significance levels of individual trials. Real-world data analyses may help to identify if there is a meaningful inter-drug difference in efficacy. Significant differences between CDK4/6i are observed for safety and tolerability outcomes.

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Conflict of interest statement

E. Amir: Honoraria from Novartis, Seagen, Gilead and AstraZeneca outside the submitted work. Michelle Nadler: Honoraria from Novartis and Exact Sciences outside the submitted work.

Figures

Figure 1
Figure 1
PRISMA flow diagram.
See this image and copyright information in PMC

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