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

PACE: A Randomized Phase II Study of Fulvestrant, Palbociclib, and Avelumab After Progression on Cyclin-Dependent Kinase 4/6 Inhibitor and Aromatase Inhibitor for Hormone Receptor–Positive/Human Epidermal Growth Factor Receptor–Negative Metastatic Breast Cancer

Findings from the PACE study show that the addition of Palbociclib to Fulvestrant was not better than Fulvestrant alone, and the addition of Avelumab to Fulvestrant improved and nearly doubled the PFS. This is compelling and should be studied further for our patients with HR+ HER2- MBC.

Ribociclib plus Endocrine Therapy in Early Breast Cancer

For your stage II – III HR+, HER2-neg breast cancer patients. Adjuvant Ribociclib + AI showed a ~3% invasive DFS benefit vs. an AI alone (90 vs 87%). This is a 3-year treatment protocol as opposed to 5 years of an AI, which some patients may appreciate.

Efficacy and Safety of Trastuzumab Deruxtecan in Patients With HER2-Expressing Solid Tumors: Primary Results From the DESTINY-PanTumor02 Phase II Trial

This is a study showing tumor agnostic activity of trastuzumab deruxtecan (T-DXd) with an all-comer overall response rate (ORR) of 37.1%, duration of response (DOR) of 11.3 months and an overall survival (OS) of 13.4 months in an otherwise heavily pre-treated group. Those with IHC-3+ derived larger benefit than 2+. Patients with ERBB2 mutations who had no expression of HER2 were excluded from the trial.

Randomized Trial of Exercise and Nutrition on Chemotherapy Completion and Pathologic Complete Response in Women With Breast Cancer: The Lifestyle, Exercise, and Nutrition Early After Diagnosis Study

There have been studies showing decreased recurrence in women who underwent curative breast surgeries (walking and yoga). This study assesses if it will affect the intensity of chemotherapy delivered. Although it did not affect it, women who underwent the program had better pathologic complete response (pCR), we need more studies to assess role of nutrition and exercise in treating cancer as we develop a wholesome approach to treat our patients, something we may be able to do in our practice.

Nine-Week Versus One-Year Trastuzumab for Early Human Epidermal Growth Factor Receptor 2–Positive Breast Cancer: 10-Year Update of the ShortHER Phase III Randomized Trial

This is a 10-year follow-up of the ShortHER study using nine weeks vs. 12 months of adjuvant trastuzumab in HR+ non-metastatic breast cancer. With long-term follow-up, non-inferiority could not be claimed statistically. Still, the DFS/OS results are identical in those patients with N0-N3 disease, while those with N4 disease seemed to have a significant difference favoring 12 months of therapy, suggesting that volume/burden of disease drives the margin of benefit in adjuvant trastuzumab therapy.