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

Author(s): Kevin Kalinsky, MD, MS¹; Melissa K. Accordino, MD, MS²; Codruta Chiuzan, PhD³; Prabhjot S. Mundi, MD²; Elizabeth Sakach, MD¹; Claire Sathe, MD²; Heejoon Ahn, MS³; Meghna S. Trivedi, MD, MS²; Yelena Novik, MD⁴; Amy Tiersten, MD⁵; George Raptis, MD⁶; Lea N. Baer, MD⁷; Sun Y. Oh, MD⁸; Amelia B. Zelnak, MD⁹; Kari B. Wisinski, MD¹⁰; Eleni Andreopoulou, MD¹¹; William J. Gradishar, MD¹²; Erica Stringer-Reasor, MD¹³; Sonya A. Reid, MD¹⁴; Anne O’Dea, MD¹⁵; Ruth O’Regan, MD¹⁶; Katherine D. Crew, MD, MS²; and Dawn L. Hershman, MD, MS²

Source: DOI: 10.1200/JCO.22.02392 Journal of Clinical Oncology

Dr. Anjan Patel's Thoughts

Interesting approach where endocrine therapy was changed after progression on 1L therapy and the ribociclib was continued.

PURPOSE

Cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) with endocrine therapy (ET) improves progression-free survival (PFS) and overall survival (OS) in hormone receptor–positive (HR+), human epidermal growth factor receptor 2–negative (HER2–) metastatic breast cancer (MBC). Although preclinical and clinical data demonstrate a benefit in changing ET and continuing a CDK4/6i at progression, no randomized prospective trials have evaluated this approach.

METHODS

In this investigator-initiated, phase II, double-blind placebo-controlled trial in patients with HR+/HER2– MBC whose cancer progressed during ET and CDK4/6i, participants switched ET (fulvestrant or exemestane) from ET used pre-random assignment and randomly assigned 1:1 to the CDK4/6i ribociclib versus placebo. PFS was the primary end point, defined as time from random assignment to disease progression or death. Assuming a median PFS of 3.8 months with placebo, we had 80% power to detect a hazard ratio (HR) of 0.58 (corresponding to a median PFS of at least 6.5 months with ribociclib) with 120 patients randomly assigned using a one-sided log-rank test and significance level set at 2.5%.

RESULTS

Of the 119 randomly assigned participants, 103 (86.5%) previously received palbociclib and 14 participants received ribociclib (11.7%). There was a statistically significant PFS improvement for patients randomly assigned to switched ET plus ribociclib (median, 5.29 months; 95% CI, 3.02 to 8.12 months) versus switched ET plus placebo (median, 2.76 months; 95% CI, 2.66 to 3.25 months) HR, 0.57 (95% CI, 0.39 to 0.85); P = .006. At 6 and 12 months, the PFS rate was 41.2% and 24.6% with ribociclib, respectively, compared with 23.9% and 7.4% with placebo.

CONCLUSION

In this randomized trial, there was a significant PFS benefit for patients with HR+/HER2– MBC who switched ET and received ribociclib compared with placebo after previous CDK4/6i and different ET.

Author Affiliations

¹Winship Cancer Institute, Emory University, Atlanta, GA²Columbia University Irving Medical Center, New York, NY³Institute of Health System Science, Feinstein Institutes for Medical Research, Northwell Health, New York, NY⁴New York University Perlmutter Cancer Center, NYU Langone Health, New York, NY⁵Icahn School of Medicine at Mount Sinai, New York, NY⁶Zucker School of Medicine—Northwell Cancer Institute, Lake Success NY⁷State University of New York at Stony Brook, Stony Brook, NY⁸Montefiore Medical Center, Bronx, NY⁹Northside Hospital, Atlanta, GA¹⁰University of Wisconsin Carbone Cancer Center, Madison, WI¹¹Weill Cornell Medicine, New York, NY¹²Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, IL¹³University of Alabama, Birmingham, Birmingham, AL¹⁴Vanderbilt University Medical Center, Nashville, TN¹⁵University of Kansas Medical Center, Westwood, KS¹⁶University of Rochester Medical Center, Rochester, NY

Low-Dose Tamoxifen in Noninvasive Breast Neoplasia: Long-Term Results From an Individual-Participant Data Pooled Analysis

Among 1,545 women included with a median follow-up of 9.4 years in postmenopausal women, breast cancer events occurred in 40 of 335 receiving low-dose tamoxifen versus 93 of 401 controls HR, 0.51, with a 10-year absolute reduction of 11.2%. Among premenopausal women, no significant reduction was observed dose was 5mg daily of 10mg every other day in ductal carcinoma in situ (DCIS) and high-risk pts. Less is as good.

Datopotamab deruxtecan in patients with untreated, advanced triple-negative breast cancer (TROPION-Breast02): a randomised, open-label, international, phase III trial

644 patients who are triple-negative breast cancer (TNBC) not candidates for immunotherapy were randomly assigned to receive Dato-DXd (n = 323) or chemotherapy (n = 321). Median progression-free survival (PFS) was 10.8 months with Dato-DXd and 5.6 months with chemotherapy. Median overall survival (OS) was 23.7 months and 18.7 months with Dato-DXd and chemotherapy, respectively HR 0.79; P = 0.029]. Treatment-related adverse events (TRAEs) of grade ≥3 were reported in 105 (33%) and 89 (29%) patients who received Dato-DXd and chemotherapy, respectively, they were more treatment discontinuation in the chemotherapy arm secondary to treatment related adverse events in 14 (4%) and 23 (7%) patients. There were no treatment-related deaths in either arm. New standard of care? Recall this is on patients not eligible for immunotherapy.

Hypo- Versus Standard Fractionated Locoregional Radiotherapy of Patients With High-Risk Breast Cancer in the Randomized Phase III Trial: The Danish Breast Cancer Group Skagen Trial 1

Less radiation (40Gy vs 50 Gy) was non inferior in preventing locoregional recurrence and distant mets, also lymphedema rates were not worse. Would love feedback from our rad onc, but it seems less is as good.

HER2CLIMB-05: A Phase III Study of Tucatinib Versus Placebo in Combination With Trastuzumab and Pertuzumab as First-Line Maintenance Therapy for HER2+ Metastatic Breast Cancer

Progression-free survival (PFS) was statistically significantly improved with addition of tucatinib versus placebo 24.9 v 16.3 months regardless of the presence/absence of BM or hormone receptor status.

Role of neoadjuvant versus adjuvant chemotherapy, dose density, and treatment schedule in biologically high-risk HR+/HER2- breast cancer: A pooled analysis of the WSG ADAPT-HR+/HER2- and PlanB trials.

1467 pts with RS > 25 and 551 with clinically (neoadjuvant cohort in ADAPT-HR+/HER2-) or pathologically N2, (longer) docetaxel-based CTx showed better distant, invasive disease-free survival in N2-3 pts patients with RS ≤25, OS was also shown in pts with RS>25 anthracycline regimens did not show a significant survival difference in high-risk HR+/HER2 whether used in neoadjuvant or adjuvant setting. So may be no anthracycline for HR+ve pts who are high risk disease.