48MO - Ribociclib (RIB) + letrozole (LET) in Asian patients (pts) with hormone receptor-positive (HR+), human epidermal growth factor receptor-2–negative (HER2−) advanced breast cancer (ABC): Subgroup analysis of the phase IIIb CompLEEment-1 trial

Background

CompLEEment-1 is a large phase IIIb trial in an expanded pt population with HR+, HER2– ABC (N = 3,246 pts). Here, we present safety and efficacy data for Asian pts from Hong Kong, India, Malaysia, Philippines, Singapore, Taiwan, and Thailand who participated in the study.

Methods

Pts with HR+, HER2– ABC, ≤1 line of prior chemotherapy (CT) and no prior endocrine therapy for ABC received RIB + LET. Study design has been reported previously (Lu J. et al, SABCS 2019, Poster P1-19-21). Primary endpoints were safety and tolerability, and secondary endpoint was efficacy.

Results

Overall, 197 Asian pts were included (6.1% of the total CompLEEment-1 population); 1.5% pts were male, 84.8% pts were <65 years (median age: 52.0 years), and 34.0% pts were premenopausal. 2.5%, 65.5%, and 12.7% pts had CNS, visceral and bone-only metastasis, 3.6% had prior CT, 5.1% were ECOG2, and 18.3% had relapsed within < 2 years of adjuvant therapy. The median duration of exposure to RIB was 16.1 months, while the median relative dose intensity was 96.9%; 2 patients (1.0%) were lost to follow-up. Adverse events (AEs) and treatment-related AEs occurred in 192 (97.5%) and 177 (89.8%) pts, while grade ≥ 3 AEs and serious AEs were reported in 142 (72.1%) and 45 (22.8%) pts, respectively. The most common all-grade and grade ≥ 3 treatment-related AEs were neutropenia (66.5% and 47.7%), leukopenia (26.4% and 12.7%), and anemia (18.8% and 4.1%). Overall, 74 (37.6%) pts had ≥ 1 dose reduction of RIB; 52 (26.4%) due to AEs. 112 (56.9%) pts permanently discontinued treatment; 15 (7.6%) due to AEs. Median time to progression was 20.3 months (95% confidence interval [CI], 15.5-22.8). For the 156 pts with measurable disease, overall response rate was 44.9% (95% CI, 36.9-53.0%), and clinical benefit rate was 68.6% (95% CI, 60.7-75.8).

Conclusions

This subgroup analysis supports the efficacy of RIB + LET in Asian pts for first-line endocrine therapy of HR+, HER2– ABC. The safety profile associated with RIB + LET was manageable with few pts discontinuing treatment due to AEs, consistent with previous phase III trials of RIB + LET.

Clinical trial identification

NCT02941926.

Editorial acknowledgement

Medical editorial assistance was provided by Sara Henriques, PhD of Healthcare Consultancy Group, LLC, and funded by Novartis Pharmaceuticals Corporation.

Legal entity responsible for the study

Novartis Pharmaceuticals.

Funding

Novartis Pharmaceuticals.

Disclosure

S. Chatterjee: Research grant/Funding (institution), Site Specific Principal Investigator: Novartis; Research grant/Funding (institution), Site Specific Principal Investigator: Roche; Research grant/Funding (institution), Site Specific Principal Investigator: Alkem; Research grant/Funding (institution), Site Specific Principal Investigator: Samsung Biopsies. M. Md Yusof: Honoraria (institution), Advisory/Consultancy, Speaker Bureau/Expert testimony, writing: AstraZeneca; Novartis; MSD; Astellas; Advisory/Consultancy, Speaker Bureau/Expert testimony, writing: Boeringher Ingelheim; Eli Lilly; Roche; Eisai; Sanofi; Genzyme; Mundi Pharma; Amgen; Advisory/Consultancy, Speaker Bureau/Expert testimony: Zuellig Pharma; Research grant/Funding (self), Principal investigator: Mundi Pharma; Honoraria (institution): Pfizer; Leadership role, executive council member: Malaysian Oncological Society; Leadership role, council member: Breast Cancer women association. T. Dejthevaporn: Honoraria (institution), Advisory/Consultancy, Speaker Bureau/Expert testimony: Novartis; Advisory/Consultancy, Speaker Bureau/Expert testimony: Eisai; AstraZeneca; Honoraria (institution), Advisory/Consultancy, Speaker Bureau/Expert testimony: Pfizer; Honoraria (institution), Advisory/Consultancy: Roche; Leadership role, Vice president: Thai Society of Clinical Oncology. W-P. Chung: Honoraria (self): Novartis; Roche; AstraZeneca; Pfizer; Amgen; Kyowa Kirin; Foundation Medicine; Chugai Pharma; Takeda; Eli Lilly; Sanofi. C.G. Galvez: Speaker Bureau/Expert testimony: Novartis; Roche; Mylan; Amgen; Leadership role, past president: Philippine Breast Cancer Society. A. Cheng: Research grant/Funding (self): AstraZeneca; Eli Lilly; Merck; Gilead Sciences; Incyte Corp.; Astellas Pharma Global Development Inc.; Ignyta; Roche; MSD; Pfizer; Novartis; Bristol-Myers Squibb; AbbVie Limited; United Therapeutics Corporation; Bayer; ARIAD Pharmaceuticals Inc. subsidiary of Takeda; Takeda; Turning Point Therapeutics Inc.. M.L.T. Abesamis-Tiambeng: Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (self): Novartis; AstraZeneca; MSD; Roche; Mylan; Eli Lilly. L. Menon-Singh; J. Wu; K. Zhou: Shareholder/Stockholder/Stock options, Full/Part-time employment: Novartis Pharmaceuticals Corporation. H. Azim: Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (self): Novartis; Roche; Pfizer; AstraZeneca; Eli Lilly; Amgen; BMS; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (self): MSD; Speaker Bureau/Expert testimony, Research grant/Funding (self): Janssen; Advisory/Consultancy: Hekma; Research grant/Funding (self): Bayer. All other authors have declared no conflicts of interest.