MAINTAIN Trial: Switching to Ribociclib After CDK4/6 Progression

Source

Source: Kalinsky K, Accordino MK, Chiuzan C, et al. Randomized Phase II Trial of Endocrine Therapy With or Without Ribociclib After Progression on Cyclin-Dependent Kinase 4/6 Inhibition in Hormone Receptor–Positive, Human Epidermal Growth Factor Receptor 2–Negative Metastatic Breast Cancer: MAINTAIN Trial. J Clin Oncol. 2023.

Phase II Randomized, Double-Blind, Placebo-Controlled Trial | HR+/HER2- Metastatic Breast Cancer

Primary Endpoint: PFS Hazard Ratio

0.57

43% Reduction in Risk of Progression or Death

(95% CI, 0.39–0.85; P = .006)

Population (N=119): HR+/HER2- mBC with progression on prior ET + CDK4/6i (87% post-palbociclib).

Randomization (1:1):
● Switched ET + Ribociclib
● Switched ET + Placebo

Median Progression-Free Survival

Significant Benefit: Median PFS nearly doubled (5.29 vs 2.76 months).

12-Month PFS Rate

Durable Response: 24.6% vs 7.4% progression-free at 1 year.

Safety Profile: Neutropenia

38%
Ribociclib Arm
(Grade 3)

0%
Placebo Arm
(Grade 3)

Febrile neutropenia was rare (n=2). Safety profile remains manageable and consistent with known ribociclib data.

Clinical Recommendation

For patients progressing on a prior CDK4/6 inhibitor (specifically palbociclib):

Switch Endocrine Therapy backbone (e.g., to Fulvestrant).
Initiate Ribociclib rather than ceasing CDK4/6 inhibition.

This delays the need for chemotherapy or PI3K/mTOR inhibitors.

AbbreviationsQuick

CBR, clinical benefit rate; CDK4/6, cyclin-dependent kinase 4/6; CDK4/6i, cyclin-dependent kinase 4/6 inhibitor; CI, confidence interval; ctDNA, circulating tumor DNA; ECOG, Eastern Cooperative Oncology Group; ET, endocrine therapy; HER2, human epidermal growth factor receptor 2; HR, hazard ratio; MBC, metastatic breast cancer; NGS, next-generation sequencing; ORR, objective response rate; OS, overall survival; PFS, progression-free survival.

Bibliography1

Kalinsky K, Accordino MK, Chiuzan C, et al. Randomized Phase II Trial of Endocrine Therapy With or Without Ribociclib After Progression on Cyclin-Dependent Kinase 4/6 Inhibition in Hormone Receptor–Positive, Human Epidermal Growth Factor Receptor 2–Negative Metastatic Breast Cancer: MAINTAIN Trial. J Clin Oncol. 2023. (DOI: 10.1200/JCO.22.02392 | link)