Final Results of RIGHT Choice: Ribociclib Plus Endocrine Therapy Versus Combination Chemotherapy in Premenopausal Women With Clinically Aggressive Hormone Receptor–Positive/Human Epidermal Growth Factor Receptor 2–Negative Advanced Breast Cancer

Author(s): Yen-Shen Lu, MD, PhD¹; Eznal Izwadi Bin Mohd Mahidin, MD²; Hamdy Azim, MD³; Yesim Eralp, MD⁴; Yoon Sim Yap, MD, PhD⁵; Seock-Ah Im, MD, PhD⁶; Julie Rihani⁷; Erhan Gokmen, MD, PhD⁸; Ahmed El Bastawisy, MD⁹; Nuri Karadurmus, MD¹⁰; Yueh Ni Lim, MD¹¹; Chun Sen Lim, MD¹²; Le Thanh Duc, MD¹³; Wei-Pang Chung, MD¹⁴; K. Govind Babu, MD¹⁵; Konstantin Penkov, MD¹⁶; James Bowles, BMedSci¹⁷; Teresa Delgar Alfaro, PharmD, MSc¹⁷; Jiwen Wu, PhD¹⁸; Melissa Gao, MD, PhD¹⁷; Khemaies Slimane, MD¹⁷; Nagi S. El Saghir, MD¹⁹

Source: https://doi.org/10.1200/JCO.24.00144

Dr. Maen Hussein's Thoughts

Myth busted. In aggressive breast cancer, no need to start chemotherapy now, ET and CKD4/6 inhibitors are better tolerated with significant progression-free survival (PFS) benefit and same response rate.

PURPOSE

A head-to-head comparison of efficacy between a cyclin-dependent kinase 4/6 inhibitor plus endocrine therapy (ET) versus combination chemotherapy (CT) has never been reported in patients with clinically aggressive hormone receptor–positive, human epidermal growth factor receptor 2–negative (HR+/HER2–) advanced breast cancer (ABC).

METHODS

In this open-label, multicenter, randomized phase II trial, pre/perimenopausal women with clinically aggressive HR+/HER2– ABC were randomly assigned 1:1 to first-line ribociclib (600 mg once daily; 3 weeks on, 1 week off) plus letrozole/anastrozole and goserelin or investigator’s choice of combination CT (docetaxel plus capecitabine, paclitaxel plus gemcitabine, or capecitabine plus vinorelbine). The primary end point was progression-free survival (PFS).

RESULTS

Among 222 patients randomly assigned to ribociclib plus ET (n = 112) or combination CT (n = 110), 150 (67.6%) had symptomatic visceral metastases, 41 (18.5%) had rapid disease progression per investigator’s judgment, and 31 (14.0%) had symptomatic nonvisceral disease. Overall, 106 (47.7%) patients had investigator-assessed visceral crisis. The median follow-up time was 37.0 months. At data cutoff, 31.3% (ribociclib arm) and 15.5% (CT arm) of patients had completed study treatment and transitioned to post-trial access. The median PFS was 21.8 months (ribociclib plus ET; [95% CI, 17.4 to 26.7]) and 12.8 months (combination CT; [95% CI, 10.1 to 18.4); hazard ratio, 0.61 [95% CI, 0.43 to 0.87]; P = .003. The overall response rates and the median time to response in the ribociclib versus CT arms, respectively, were 66.1% and 61.8% and 4.9 months and 3.2 months (hazard ratio, 0.76 [95% CI, 0.55 to 1.06]). Lower rates of symptomatic adverse events were observed in the ribociclib versus CT arm.

CONCLUSION

First-line ribociclib plus ET showed a significant PFS benefit, similar response rates, and better tolerability over combination CT in patients with clinically aggressive HR+/HER2– ABC.

Author Affiliations

¹National Taiwan University Hospital, Taipei, Taiwan; ²Hospital Kuala Lumpur, Kuala Lumpur, Malaysia; ³School of Medicine, Cairo University, Cairo, Egypt; ⁴Acıbadem Research Institute of Senology, Acıbadem University, Istanbul, Turkey; ⁵National Cancer Centre Singapore, Singapore; ⁶Seoul National University Hospital, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea; ⁷Independent Patient Advocate, Amman, Jordan; ⁸Ege University Faculty of Medicine, Izmir, Turkey; ⁹National Cancer Institute, Cairo University, Giza, Egypt; ¹⁰Gülhane Education and Research Hospital, University of Health Sciences, Ankara, Turkey; ¹¹Sarawak General Hospital, Kuching, Sarawak, Malaysia; ¹²Hospital Sultan Ismail, Johor Bharu, Johor Darul Ta’zim, Malaysia; ¹³National Cancer Hospital, Hanoi, Vietnam; ¹⁴National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan; ¹⁵HCG Curie Centre of Oncology and Kidwai Memorial Institute of Oncology, Bangalore, India; ¹⁶Private Medical Institution Euromedservice, St Petersburg, Russian Federation; ¹⁷Novartis Pharma AG, Basel, Switzerland; ¹⁸Novartis Pharmaceuticals Corporation, East Hanover, NJ; ¹⁹American University of Beirut Medical Center, Beirut, Lebanon

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.