Kevin Kalinsky, MD, MS, spoke about future studies following results from the phase 2 MAINTAIN trial of ribociclib with or without endocrine therapy and after progression on a CDK4/6 inhibitor for patients with unresectable or metastatic hormone receptor–positive, HER2-negative breast cancer.
Kevin Kalinsky, MD, MS, associate professor in the Department of Hematology and Medical Oncology at Emory University School of Medicine; Louisa and Rand Glenn Family Chair in Breast Cancer Research; director of Glenn Family Breast Center; and director of Breast Medical Oncology at the Winship Cancer Institute of Emory University spoke with CancerNetwork® at the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting. Kalinsky spoke about future analyses and studies following results from the phase 2 MAINTAIN trial (NCT02632045) which assessed ribociclib (Kisqali) with or without endocrine therapy after progression on a CDK4/6 inhibitor for patients with unresectable or metastatic hormone receptor–positive, HER2-negative breast cancer.
Kalinsky also discussed the limitations for single-agent treatment in the post-CDK4/6 setting, and the benefit of the MAINTAIN regimen in this setting.
For MAINTAIN, there are some additional analyses that we will do in the future. There’s a strong correlate component to the study where we will look at tumor tissue, as well as ctDNA [circulating tumor DNA] and other blood markers to see who’s responding and who’s not. We discussed some of that during the ASCO presentation, but there’s additional work that we are planning on reporting. Overall [in the field], there are additional randomized trials that we are awaiting, including the [phase 2] PACE study [NCT03147287], which is a study of palbociclib [Ibrance] after [CDK inhibitors and endocrine therapy]. There is also the [phase 2] PALMIRA study [NCT03809988], which is looking at the same question. There’s an ongoing randomized phase 3 trial that’s looking at abemaciclib [Verzenio], post CDK4/6 inhibition, called the [phase 3] postMONARCH study [NCT05169567], which is currently accruing patients.
I think there are 2 takeaway points from this research. If we look at patients after they’ve had a CDK4/6 inhibitor, giving a single agent hormonal therapy, the median progression-free survival in this study was about 2.76 months [in the placebo arm]. We’ve seen [similar] rates in other studies in this setting like the [phase 2] VERONICA study [NCT03584009] and the [phase 3] EMERALD study [NCT03778931]. Single agent activity with hormonal therapies is limited. The other thing I want to mention just in terms of CDK4/6 inhibitors after a CDK4/6 inhibitor is that it’s promising to see that all the observational data and preclinical data, that we’ve seen is in a randomized trial. This is the first proof of principle study demonstrating that there is benefit of CDK4/6 inhibition after CDK4/6 inhibition, and also understanding that we’re waiting for other randomized trials.
Kalinsky K, Accordino MK, Chiuzan C, et al. A randomized, phase II trial of fulvestrant or exemestane with or without ribociclib after progression on anti-estrogen therapy plus cyclin-dependent kinase 4/6 inhibition (CDK 4/6i) in patients (pts) with unresectable or hormone receptor–positive (HR+), HER2-negative metastatic breast cancer (MBC): MAINTAIN trial. J Clin Oncol. 2022;40(suppl 17):LBA1004. doi:10.1200/JCO.2022.40.17_suppl.LBA1004