16 Primary Results From the Randomized Phase II RIGHT Choice Trial of Premenopausal Patients With Aggressive HR+/HER2− Advanced Breast Cancer Treated With Ribociclib + Endocrine Therapy vs Physician’s Choice Combination Chemotherapy

Background

Chemotherapy (CT) is the standard of care for advanced breast cancer (ABC) with clinically aggressive features that include rapidly progressing or highly symptomatic disease and life-threatening visceral crisis, which requires rapid disease control. Combination CT is associated with a higher overall response rate (ORR) and longer progression-free survival (PFS) than single-agent CT and may be preferred for those who have a critical disease condition and may tolerate potentially toxic treatment. Ribociclib (RIB) + endocrine therapy (ET) demonstrated statistically significant PFS and overall survival (OS) benefits over ET alone in 3 Phase 3 clinical trials (MONALEESA-2, -3, and -7) in patients with hormone receptor−positive, human epidermal growth factor 2 receptor− negative (HR+/HER2−) ABC, including patients with visceral metastases and a high tumor burden. No data have been published on a head-to-head comparison of cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitor + ET vs combination CT in the patient population with aggressive HR+/HER2− disease. Here we report the prespecified primary analysis of PFS and key secondary end points from the randomized, open-label, multinational, Phase 2 RIGHT Choice trial.

Materials and Methods

The prespecified PFS analysis was planned after disease progression or death in approximately 110 patients. The study had 80% power to detect a hazard ratio (HR) of 0.67 at a 1-sided α level of 10%. Stratified Cox regression was used to estimate the HR for PFS, time to treatment failure (TTF), and time to response (TTR). TTF was defined as the time from randomization to progression, death, change to other anticancer therapy, or discontinuation. TTR was defined as the time from the date of randomization to the first documentation of either complete response (CR) or partial response (PR) without confirmation (confirmation imaging was not required according to study protocol). The efficacy analyses were performed in all randomized patients, while the safety analysis was performed in all patients who received ≥1 treatment dose. Ten patients randomized to the combination CT arm were not included in the safety set as they did not receive any study treatment; 9 of these patients withdrew consent following knowledge of randomization to the CT arm, and 1 was withdrawn based on the physician’s decision. OS data were immature at the data cutoff (April 12, 2022).

Results

222 pts (112 RIB+ET; 110 CT) were randomized, including pts with symptomatic visceral mets (n=150; 67.6%), rapid disease progression (n = 41; 18.5%), and markedly symptomatic non-visceral mets (n = 31; 14.0%). 116 pts (52.3%) had visceral crises based on guidelines and PI’s judgment. A majority (n = 190; 85.6%) had tumors that were ≥50% ER+. Median follow-up was 24.1 mo; 45.5% and 23.6% of pts remained on treatment in the RIB+ET and combo CT arms. The primary end point was met, with a statistically significant PFS benefit of ≈ 1 year for RIB+ET vs combo CT (mPFS, 24.0 vs 12.3 mo; hazard ratio [HR], 0.54; 95% CI, 0.36-0.79; P = .0007). OS data were immature at data cutoff. mTTF was ≈ 10 mo longer for RIB+ET vs CT (18.6 vs 8.5 mo; HR, 0.45; 95% CI, 0.32-0.63). ORR was similar for RIB+ET vs CT (65.2% vs 60.0%, respectively). No new safety signals were observed in pts on RIB. Lower rates of serious treatment-related adverse events (TRAEs; 1.8% vs 8.0%) and discontinuations of any component of study treatment due to TRAEs (7.1% vs 23.0%) were seen with RIB+ET vs CT, respectively. AEs observed with combination CT were consistent with the published data.

Conclusions

RIGHT Choice is the first prospective study comparing a CDK4/6 inhibitor + ET with combination CT and demonstrating the PFS superiority of RIB+ET over combination CT in patients with HR+/HER2− ABC with aggressive clinical features of rapidly progressing or highly symptomatic disease, including life-threatening visceral crisis

First-line RIB+ET demonstrated a statistically significant PFS benefit (≈ 1 year longer) vs combination CT (24.0 vs 12.3 months; HR, 0.54) in pre-/perimenopausal patients with aggressive HR+/HER2− ABC.

RIB+ET also showed longer TTF than combination CT with similar TTR and ORR between the 2 treatment groups, matching the high tumor response rate seen with combination CT. No new safety signals were observed with RIB+ET

Compared with RIB + ET, combination CT was associated with higher rates of treatment-related AEs, many of which impact QOL.

First-line RIB+ET offers an efficacious, clinically meaningful treatment option for patients with aggressive HR+/HER2− ABC, obviating the need for combination CT and its related toxicities.

AFFILIATIONS:

Melissa Gao,¹ Yen-Shen Lu,² Eznal Izwadi Bin Mohd Mahidin,³ Hamdy Azim,⁴ Yesim Eralp,⁵ Yoon-Sim Yap,⁶ Seock-Ah Im,⁷ Julie Rihani,⁸ James Bowles,¹ Teresa Delgar Alfaro,¹ Jiwen Wu,⁹ Khemaies Slimane,¹ Nagi El Saghir¹⁰

¹Novartis Pharma AG, Basel, Switzerland.

²National Taiwan University Hospital, Taipei, Taiwan.

³Hospital Kuala Lumpur, Kuala Lumpur, Malaysia.

⁴School of Medicine, Cairo University, Cairo, Egypt.

⁵Acibadem Research Institute of Senology, Acibadem University, Istanbul, Turkey.

⁶National Cancer Centre Singapore, Singapore.

⁷Seoul National University Hospital, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.

⁸Patient advocate.

⁹Novartis Pharmaceuticals Corporation, East Hanover, NJ.

¹⁰American University of Beirut Medical Center, Beirut, Lebanon.