<p>CDK4/6 inhibitors have emerged as a promising addition to hormone therapy for high-risk early-stage HR+/HER2- breast cancer. Studies presented at the <strong>2025 ASCO Annual Meeting</strong> highlighted some of the latest data on CDK4/6 inhibitors in this patient population.</p> <p><br></p> <p><em>Following these presentations, featured expert Melinda L. Telli, MD, FASCO, was interviewed by </em>Conference Reporter<em> Associate Editor-in-Chief Christopher Ontiveros, PhD. Clinical perspectives from Dr Telli on these findings are presented here.</em></p>

Two trials led to the US Food and Drug Administration (FDA) approvals of CDK4/6 inhibitors for high-risk early-stage HR+/HER2- breast cancer. The first is the phase 3 monarchE study, which enrolled patients with high-risk, early-stage, HR+/HER2-, lymph node–positive breast cancer. The trial compared hormone therapy with or without the CDK4/6 inhibitor abemaciclib for 2 years. The second is the phase 3 NATALEE trial, which looked at hormone therapy with or without ribociclib for 3 years in patients with early-stage HR+/HER2- breast cancer. NATALEE enrolled a broader population of patients in that, while some patients had lymph node–positive disease, others did not, although they had tumors with other high-risk features. Both trials reported improvements in their primary end points of invasive disease-free survival when the CDK4/6 inhibitor was used, and both abemaciclib and ribociclib are now FDA approved for high-risk early-stage HR+/HER2- breast cancer.

<br>

At ASCO 2025, a subgroup analysis from the phase 3 NATALEE trial looking at the efficacy and safety of ribociclib according to menopausal status and age was presented by Kevin Kalinsky, MD, FASCO, MS (abstract 516). The analysis found that there was a pretty consistent degree of benefit with ribociclib across the younger premenopausal and older postmenopausal patients, although premenopausal patients appeared to have a slightly greater benefit. The study also looked by age and found a consistent signal across the different age groups. In terms of toxicities, investigators reported similar side-effect profiles, and younger patients were less likely to discontinue treatment compared with older patients. This analysis provides reassurance about the overall magnitude and consistency of benefit with adjuvant ribociclib across menopausal status and age groups.

<br>

Another study at ASCO 2025 that I found interesting was the phase 2 TRADE study, which was presented by Erica L. Mayer, MD, MPH, FASCO (abstract 517). This study enrolled patients scheduled to receive adjuvant treatment with abemaciclib. Unlike the monarchE trial, in which patients initiated treatment at the target dose of 150 mg twice daily, followed by a dose reduction if toxicities occurred, the TRADE study used a dose ramp-up strategy. Patients started at 50 mg twice daily for 2 weeks, then increased the dose to 100 mg twice daily for 2 weeks, and, finally, increased the dose again to the target dose of 150 mg twice daily, as tolerated. The TRADE study found that fewer patients discontinued abemaciclib treatment. In addition, more were able to receive the target dose of 150 mg at 12 weeks with a ramp-up approach, at 70.8%, compared with approximately 60% in monarchE. Although the TRADE study is a small nonrandomized trial, the dose ramp-up strategy is worth considering.

<br>

Finally, data from the first interim analysis of the large phase 3 DAWNA-A study were presented at ASCO 2025 by Zhi-Ming Shao, MD, PhD (abstract 515). This study is evaluating dalpiciclib, an investigational CDK4/6 inhibitor that is available in China, in more than 5000 patients with high-risk early-stage HR+/HER2- breast cancer with lymph node involvement; the patient population was similar to the monarchE population. Patients are receiving 2 years of treatment with dalpiciclib and hormone therapy vs placebo with hormone therapy. At the first interim analysis, after a median follow-up of 20.3 months, there was a 2.9% difference in 3-year invasive disease-free survival, which is similar to the data that we saw from NATALEE.