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Clinical Trial
. 2022 Nov;17(6):615-625.
doi: 10.1007/s11523-022-00913-x. Epub 2022 Sep 24.

Safety and Efficacy of Ribociclib in Combination with Letrozole in Patients with HR+, HER2- Advanced Breast Cancer: Results from the Italian Subpopulation of Phase 3b CompLEEment-1 Study

Michelino De Laurentiis  1 , Roberta Caputo  2 , Manuelita Mazza  3 , Mauro Mansutti  4 , Riccardo Masetti  5 , Zelmira Ballatore  6 , Rosalba Torrisi  7 , Andrea Michelotti  8 , Alberto Zambelli  9 , Antonella Ferro  10 , Daniele Generali  11 , Patrizia Vici  12 , Luigi Coltelli  13 , Alessandra Fabi  14 , Paolo Marchetti  15 , Alberto Ballestrero  16 , Simon Spazzapan  17 , Antonio Frassoldati  18 , Maria Giuseppina Sarobba  19 , Donatella Grasso  20 , Claudio Zamagni  21
Affiliations
Clinical Trial

Safety and Efficacy of Ribociclib in Combination with Letrozole in Patients with HR+, HER2- Advanced Breast Cancer: Results from the Italian Subpopulation of Phase 3b CompLEEment-1 Study

Michelino De Laurentiis et al. Target Oncol. 2022 Nov.

Abstract

Background: Ribociclib plus letrozole demonstrated manageable safety and efficacy profiles in hormone receptor-positive (HR+), human epidermal growth factor receptor-2-negative (HER2-) advanced breast cancer (ABC) in the Phase 3b CompLEEment-1 trial.

Objective: To evaluate the safety and efficacy of ribociclib plus letrozole in the Italian subpopulation with HR+, HER2- ABC from the CompLEEment-1 trial.

Patients and methods: Patients with HR+, HER2- ABC received ribociclib (600 mg/day, 3 weeks on/1 week off) plus letrozole (2.5 mg/day) while men and premenopausal women additionally received goserelin. Patients were allowed with ≤ 1 line of prior chemotherapy and an Eastern Cooperative Oncology Group performance status of ≤ 2. The primary outcome included safety and tolerability.

Results: Of the 554 Italian patients, 246 (44.4 %) patients completed treatment. The reasons for treatment discontinuation included progressive disease (PD; 36.6 %), adverse events (AEs; 11.9 %), and death (1.6 %). All-grade AEs and grade ≥ 3 AEs occurred in 98.9 % and 77.8 % patients, respectively. The most common treatment-related AEs were neutropenia (73.6 %), followed by leukopenia (32.1 %), and nausea (25.3 %). The overall response rate was 28.2 % (95 % confidence interval [CI], 24.4-32.1); clinical benefit rate was 71.7 % (95 % CI, 67.7-75.4); and median time to progression was 26.7 months (95 % CI, 24.8-non-estimable). Health-related quality of life scores were maintained during treatment.

Conclusion: The safety and efficacy profiles of ribociclib plus letrozole in the Italian subpopulation was found to be consistent with the CompLEEment-1 global population result, MONALEESA-2, and MONALEESA-7 outcomes, which reaffirm ribociclib plus letrozole as the frontline treatment option in patients with HR+, HER2- ABC.

Trial registration number and date of registration: NCT02941926 (30 November 2016).

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Conflict of interest statement

Michelino De Laurentiis participated in the advisory board and received grants, consulting fees and honoraria from Novartis, Roche, MSD, Astra Zeneca, Daiichi Sankyo, Seagen, Eli Lilly, and Pfizer. Manuelita Mazza participated in the advisory board and received grants, consulting fees and honoraria from Novartis, Pfizer, Astra Zeneca, Eli Lilly, Gentili, and Roche. Mauro Mansutti participated in the advisory board of Amgen, Astra Zeneca, Eli Lilly, Gentili, MSD Italia, Novartis, Pfizer, Roche; honoraria from Pierre Fabre; reimbursement of travel or accommodation expenses from Eisai, Novartis, Pfizer, Pierre Fabre, Roche. Zelmira Ballatore received honoraria from Ipsen, Novartis, Roche. Rosalba Torrisi received honoraria from Astra Zeneca, Eisai, Pfizer, Eli Lilly, and Gentili. Rita De Sanctis Novartis, Amgen, Kyowa Kirin, and Eisai. Alberto Zambelli participated in the advisory board of Novartis, Pfizer, Astra Zeneka, Daiichi Sankyo, MSD, Eli Lilly; received honoraria from Novartis, Pfizer, Astra Zeneka, Daiichi Sankyo, MSD, Eli Lilly, Exact Sciences. Antonella Ferro received personal fees from Novartis and Eli Lilly. Daniele Generali participated in advisory board for Lilly, Novartis, Pierre Fabre; received honoraria from Novartis, Pfizer, Lilly, Astra Zeneca, ESAI, Istituto Gentili; reimbursement of travel or accommodation expenses from Novartis, Lilly, and Pierre-Febre. Patrizia Vici participated in advisory board for Novartis, Eisai; and received honoraria from Pfizer, Novartis, Gentili, Lilly, EISAI, Roche. Paolo Marchetti received honoraria from Roche, BMS, MSD, Novartis, Pfizer, Pierre Fabre; reimbursement support for congress attendance from BMS, Roche, Pierre Fabre; received grants to institution from Roche, BMS, Pfizer, Incyte, Novartis, Takeda, MSD, Pierre Fabre. Simon Spazzapan participated in the advisory board of Novartis, Astra Zeneca, Daichii, Sankyo and received honoraria from Novartis, Pfizer, Astra Zeneka, Daiichi Sankyo, MSD, Eli Lilly. Antonio Frassoldati participated in the advisory board and received personal fees from Novartis, Astra Zeneca, Pfizer, Lilly, Roche, Daichii, Seagen, Amgen. Maria Giuseppina Sarobba participated in the advisory board of Novartis, Pierre Fabre, MSD, and received honoraria from Novartis, Pfizer, Lilly, Astra Zeneca, MSD, Astellas. Donatella Grasso is employed by Novartis. Claudio Zamagni has received honoraria for consulting or advisory roles from Astra Zeneca, Eisai, Novartis, Pfizer, PharmaMar, Pierre Fabre, and Roche; research funding from AbbVie, Array BioPharma, Astra Zeneca, Celgene, Medivation, Morphotek, Novartis, Pfizer, Roche, and Roche/Genentech; reimbursement for travel, accommodations, or expenses from Celgene, Novartis, Pierre Fabre, and Roche. Roberta Caputo, Riccardo Masetti, Andrea Michelotti, Luigi Coltelli, Alessandra Fabi, and Alberto Ballestrero declared no conflict of interest.

Figures

Fig. 1
Fig. 1
Treatment-related adverse events (> 5 %) by preferred term for subgroup
Fig. 2
Fig. 2
Kaplan–Meier plot of time to progression as per local investigator's assessment for subgroup
Fig. 3
Fig. 3
Kaplan–Meier plot of time to first occurrence of a clinically relevant deterioration, defined as a ≥ 7-point decrease in FACT-B total scores (patient-reported outcomes analysis set)
See this image and copyright information in PMC

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