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

Overall Survival with Inavolisib in PIK3CA-Mutated Advanced Breast Cancer

The INAVO120 trial assessed inavolisib + palbociclib–fulvestrant vs placebo plus palbociclib–fulvestrant in PIK3CA-mutated, HR-positive, HER2-negative advanced breast cancer, showing significant improvements in progression-free survival (PFS) (15.0 vs 7.3 months) and overall survival (OS) (34.0 vs 27.0 months). The triplet regimen achieved a higher overall response rate (ORR) (62.7% vs 28.0%), establishing it as a potential new standard for this endocrine-resistant population. Notably, side effects like hyperglycemia, stomatitis, diarrhea, and ocular effects were more frequent with inavolisib.

Chemotherapy-free neoadjuvant pembrolizumab combined with trastuzumab and pertuzumab in HER2-enriched early breast cancer (WSG-KEYRICHED-1): a single-arm, phase 2 trial

The WSG-KEYRICHED-1 phase II trial evaluated a chemotherapy-free neoadjuvant regimen of pembrolizumab plus trastuzumab and pertuzumab in HER2-enriched early breast cancer, achieving a pathological complete response (pCR) rate of 46.5% (95% CI 31.2–62.6%). No survival data (e.g., EFS or OS) were reported, but the regimen showed an acceptable safety profile with no new cardiac toxicity signals. The chemo-free approach suggests promising potential for de-escalation in this subtype, but we’ll need randomized trials to confirm its efficacy and safety.

Metronomic Capecitabine Plus Aromatase Inhibitor as Initial Therapy in Patients With Hormone Receptor–Positive, Human Epidermal Growth Factor Receptor 2–Negative Metastatic Breast Cancer: The Phase III MECCA Trial

Metronomic dose: low dose cytotoxic therapy at high frequency was studied in combination with an AI (cape at 500mg TID) and showed superiority over AI single agent, this may be an option for patients not tolerating CKD4/6 inhibitors.

Adjuvant Atezolizumab for Early Triple-Negative Breast Cancer

In summary: It did not work in those patients with stages II-III.

Abemaciclib Plus Fulvestrant in Advanced Breast Cancer After Progression on CDK4/6 Inhibition: Results From the Phase III postMONARCH Trial

Yet another combination to consider after CDK4/6i + ET in HR+ MBC!