RIB, an oral, selective CDK4/6 inhibitor, is approved for use in combination with endocrine therapy in women with HR+, HER2– ABC in the USA and EU. CompLEEment-1, an ongoing single-arm phase 3b trial, evaluated first-line RIB + LET with broad inclusion criteria to reflect a real-world HR+, HER2– ABC population. Here we report interim safety and efficacy in pts with VM or BOM.
Pts received RIB (600 mg/day, 3 weeks on/1 week off) + LET (2.5 mg/day). Men and premenopausal women also received goserelin (3.6 mg subcutaneously) or leuprolide (7.5 mg intramuscular injection) every 28 days. The primary outcome (safety) and key secondary outcomes (time to progression [TTP], overall response rate [ORR], and clinical benefit rate [CBR]) were reported for two subgroups: pts with VM and pts with BOM.
Of the 3,246 pts, 1,983 (61.1%) had VM; among this group, 1,309 (66.0%) also had bone metastases. BOM were present in 706 pts (21.7%). At data cut-off (Aug 8, 2018), median duration of RIB exposure was 8.0 months in pts with VM and 8.8 months in pts with BOM. Median duration of study follow-up was 10.35 months. In pts with VM, the most common adverse events were neutropenia (57.2%), nausea (35.2%), and fatigue (22.5%); 12.5% discontinued due to AEs. Estimated 12-month event-free probability (EFP) in pts with VM was 63.1% (95% confidence interval [CI], 59.5-66.6%), ORR was 30.7% (95% CI, 28.4-33.1%) and CBR was 62.8% (95% CI, 60.3-65.2%). In pts with BOM, the most common AEs were neutropenia (57.8%), nausea (33.3%), and fatigue (21.5%); 11.8% discontinued due to AEs. The estimated 12-month EFP in the BOM subgroup was 82.8% (95% CI, 78.6-86.3%), ORR was 20.6% (95% CI, 14.8-27.3%), and CBR was 69.1% (95% CI, 61.7-75.9%).
Safety and efficacy outcomes in this post hoc analysis support the use of RIB + LET in pts with VM and BOM. Pts with BOM were less likely to have an objective tumor response but more likely to be progression free at 12 months, consistent with the more favorable prognosis of BOM compared with non-osseous metastases.
NCT02941926.
Medical editorial assistance was provided by Joe Hodgson of Healthcare Consultancy Group, LLC, and funded by Novartis Pharmaceuticals Corporation.
Novartis.
Novartis Pharmaceuticals.
M. De Laurentiis: Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Personal Fees, Speaker’s Honoraria, Advisory Board Honoraria: Pfizer; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Personal Fees, Speaker’s Honoraria, Advisory Board Honoraria: Novartis; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Personal Fees, Speaker’s Honoraria, Advisory Board Honoraria: Roche; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Personal Fees, Speaker’s Honoraria, Advisory Board Honoraria: Celgene; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Personal Fees, Speaker’s Honoraria, Advisory Board Honoraria: AstraZeneca; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Personal Fees, Speaker’s Honoraria, Advisory Board Honoraria: Eisai; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Personal Fees, Speaker’s Honoraria, Advisory Board Honoraria: Eli Lilly; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Personal Fees, Speaker’s Honoraria, Advisory Board Honoraria: Amgen. A. Ring: Honoraria (self), Advisory / Consultancy: Roche; Honoraria (self), Advisory / Consultancy: Genomic Health; Honoraria (self), Advisory / Consultancy: Eli Lilly; Honoraria (self), Advisory / Consultancy: Novartis; Honoraria (self), Advisory / Consultancy: Pfizer. M. Campone: Honoraria (institution), Advisory / Consultancy, Speaker Bureau / Expert testimony: Novartis; Advisory / Consultancy: Eli Lilly; Honoraria (institution), Advisory / Consultancy: Sanofi; Honoraria (institution), Advisory / Consultancy: Servier; Honoraria (institution), Advisory / Consultancy: Accord; Honoraria (institution), Advisory / Consultancy: Pfizer; Honoraria (institution), Advisory / Consultancy: Abbvie. T. Bachelot: Honoraria (self), Travel / Accommodation / Expenses: Roche; Honoraria (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: Novartis; Honoraria (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: AstraZeneca; Honoraria (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: Pfizer. W. Jacot: Honoraria (self): Pierre Fabre; Advisory / Consultancy: Pfizer; Advisory / Consultancy: Roche; Research grant / Funding (institution): AstraZeneca. P. Marchetti: Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): Novartis; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): BMS; Advisory / Consultancy, Speaker Bureau / Expert testimony: AstraZeneca; Advisory / Consultancy, Speaker Bureau / Expert testimony: Incyte; Advisory / Consultancy, Speaker Bureau / Expert testimony: Molteni; Advisory / Consultancy, Speaker Bureau / Expert testimony, Leadership role, Research grant / Funding (institution): Roche; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): MSD; Research grant / Funding (institution): Janssen. C. Timcheva: Advisory / Consultancy, Speaker Bureau / Expert testimony: Roche; Speaker Bureau / Expert testimony: AstraZeneca; Advisory / Consultancy, Speaker Bureau / Expert testimony: Novartis; Speaker Bureau / Expert testimony: MSD; Speaker Bureau / Expert testimony: Servie. A. Gombos: Research grant / Funding (institution): Novartis. All other authors have declared no conflicts of interest.