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28-10-2020 | Oncology | News | Article

Meta-analysis confirms CDK4/6 inhibitor benefit for HR-positive metastatic breast cancer

Author:
Shreeya Nanda

medwireNews: The addition of CDK4/6 inhibitors to endocrine therapy is associated with improved outcomes in patients with hormone receptor (HR)-positive, HER2-negative metastatic breast cancer, shows a meta-analysis.

“These results may aid physicians in selecting an effective therapeutic regimen” for this patient population, say Jiuda Zhao, from Qinghai University in Xining, China, and colleagues.

The study, published in JAMA Network Open, included one phase 2 and eight phase 3 randomized clinical trials that investigated the addition of a CDK4/6 inhibitor (ribociclib, palbociclib, or abemaciclib) to endocrine therapy in a total of 5043 patients with HR-positive metastatic breast cancer.

Analysis of overall survival (OS) data from the six trials that reported on this endpoint showed a significant benefit for patients who did versus did not receive a CDK4/6 inhibitor alongside endocrine therapy, with a hazard ratio (HR) for survival of 1.33.

The addition of CDK4/6 inhibitors was associated with a significant OS gain regardless of whether participants were premenopausal (HR=1.32) or postmenopausal (HR=1.34), had visceral (HR=1.31) or bone-only (HR=1.22) metastases, were aged at least 65 years (HR=1.38) or were younger (HR=1.25), or received treatment in the first- (HR=1.35) or second-line (HR=1.30).

“The survival data, references, and subgroup analyses included in the present meta-analysis are more comprehensive, complete, and contain a larger sample size compared with those previously published meta-analyses,” highlight the researchers.

All nine studies also reported on progression-free survival and objective response rate (ORR), and both these endpoints were also significantly boosted when a CDK4/6 inhibitor was added to endocrine therapy, with HRs of 1.84 and 2.02, respectively.

Zhao and colleagues note, however, that the use of CDK4/6 inhibitors was also associated with a significant increase in the risk for grade 3 or 4 adverse events (AEs), specifically neutropenia (HR=57.05), leukopenia (HR=36.36), and diarrhea (HR=4.97).

But these “grade 3/4 AEs may be controlled through experience, medication, or dose adjustment,” they add.

The investigators also point out the three CDK4/6 inhibitors had differing AE profiles, such that palbociclib and ribociclib were primarily associated with hematologic toxicity and abemaciclib with diarrhea and fatigue.

On the whole, the heterogeneity across studies was low, with the exceptions being the assessment of ORR and grade 3–4 diarrhea, for which the heterogeneity was high, says the team.

The authors of a related commentary note that this meta-analysis and other meta-analyses of the same clinical trials “have largely arrived at similar conclusions.”

James Martin and Lori Goldstein, both from University Hospitals Seidman Cancer Center in Cleveland, Ohio, USA, conclude that “[t]hese data support the current clinical practice of discussing the potential benefits of CDK4/6 inhibitors with nearly all patients living with HR-positive, [HER2]-negative metastatic cancer, as recommended by the National Comprehensive Cancer Network guidelines.”

medwireNews is an independent medical news service provided by Springer Healthcare Ltd. © 2020 Springer Healthcare Ltd, part of the Springer Nature Group

JAMA Netw Open 2020; 3: e2020312

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