Continued CDK 4/6 inhibition after breast cancer progression may benefit some patients
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CHICAGO — Ribociclib extended PFS among patients with hormone receptor-positive, HER2-negative metastatic breast cancer who switched endocrine therapy and received the drug after progression on a CDK 4/6 inhibitor, study results showed.
The findings of the double-blind, randomized phase 2 MAINTAIN trial, presented at ASCO Annual Meeting, demonstrated the potential benefit of continued CDK 4/6 inhibition with hormone therapy for these patients.
“This is the first randomized trial to show the benefit of ribociclib (Kisqali, Novartis) and switching endocrine therapy after CDK 4/6 inhibitor progression,” Kevin Kalinsky, MD, MS, director of breast medical oncology and the Glenn Family Breast Center at Winship Cancer Institute of Emory University, told Healio. “Ribociclib plus endocrine therapy led to a statistically significant improvement in PFS compared with placebo plus endocrine therapy in patients with tumor progression following prior CDK 4/6 inhibitor.”
Background and methods
Inhibition of cyclin-dependent kinases 4 and 6 (CDK 4/6) in combination with endocrine therapy has been shown to extend PFS and OS among patients with hormone receptor-positive, HER2-negative metastatic breast cancer.
“[However,] the anti-proliferative effect of CDK 4/6 inhibition can reverse upon discontinuation,” Kalinsky said. “Observational data support the potential benefit of treating with a CDK 4/6 inhibitor and switching endocrine therapy after CDK 4/6 inhibitor progression; however, no prospective randomized trials reported with this approach.”
The MAINTAIN trial examined the effectiveness of fulvestrant or exemestane with or without the CDK 4/6 inhibitor ribociclib among 119 patients (median age, 57 years; 99.2% women; 74% white, 17.6% Hispanic) with hormone receptor-positive, HER2-negative metastatic breast cancer that progressed during CDK 4/6 inhibition and endocrine therapy.
Most patients (83%) received fulvestrant as endocrine therapy, whereas 17% received exemestane. With regard to previous CDK 4/6 inhibitors, 84% received palbociclib (Ibrance, Pfizer), 11% received ribociclib, 2% received abemaciclib (Verzenio, Eli Lilly) and 3% received palbociclib and another CDK 4/6 inhibitor.
Researchers randomly assigned patients 1:1 to fulvestrant (for those who previously received exemestane) or exemestane (for those who previously received fulvestrant) with or without ribociclib, administered orally at a dose of 600 mg daily in a 3-weeks-on, 1-week-off schedule. Those who had not received either of the endocrine therapies received fulvestrant or exemestane per investigator discretion, with use of fulvestrant encouraged.
PFS, defined as time from random assignment to disease progression or death, served as the primary endpoint.
Key findings
Results showed a statistically significant increase in PFS among patients who received endocrine therapy with ribociclib vs. with placebo (median, 5.33 months vs. 2.76 months; HR = 0.56; 95% CI, 0.37-0.83). Researchers observed similar PFS results among the subset of patients who received fulvestrant with vs. without ribociclib (median, 5.29 months vs. 2.76 months; HR = 0.59; 95% CI, 0.38-0.91).
“Fulvestrant alone had a limited median PFS after CDK 4/6 inhibitor progression, consistent with recent trials in the same space,” Kalinsky told Healio.
The ribociclib group had higher rates of PFS at 6 months (42% vs. 24%) and at 12 months (25% vs. 7%).
A higher proportion of patients in the ribociclib group experienced dose interruptions (53% vs. 20%) and dose reductions (23% vs. 8.5%) due to adverse events.
Treatment-related adverse events were mostly low grade and included neutropenia (72% ribociclib vs. 15% placebo), anemia (23% vs. 22%) and thrombocytopenia (25% vs. 5%). The ribociclib group had a higher rate of grade 3 neutropenia (38% vs. 0%), as expected, but only two patients in that group experienced febrile neutropenia, compared with none in the placebo group.
Next steps
Analyses of additional biomarker data are ongoing, Kalinsky told Healio.
“Also, we await the results of other randomized trials, including PACE [Palbociclib After CDK and Endocrine Therapy] and the ongoing postMONARCH trials [of abemaciclib with or without fulvestrant],” he said.
Perspective
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Sayeh Lavasani, MD, MS
This study shows meaningful benefit of ribociclib among patients who show disease progression on any CDK 4/6 inhibitor. This is a practice-changing clinical trial that confirms previous observational studies indicating benefit of continuation of CDK 4/6 inhibition beyond disease progression.
Hopefully with these results, the insurance coverage will broaden to include ribociclib for patients who have disease progression on any CDK 4/6 inhibitor.
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Kalinsky K, et al. Abstract LBA1004. Presented at: ASCO Annual Meeting; June 3-7, 2022; Chicago.
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