331P Impact of ribociclib (RIB) dose reduction on overall survival (OS) in patients (pts) with HR+/HER2− advanced breast cancer (ABC) in MONALEESA (ML) -3 and -7

RIB + endocrine therapy (ET) had a significant OS benefit vs. placebo (PBO) in pts with HR+/HER2− ABC in the ML-3 (postmenopausal pts; HR, 0.71; P = .00973; Slamon et al. N Engl J Med. 2020) and ML-7 (premenopausal pts; HR, 0.72; P = .00455; Im et al. N Engl J Med. 2019) trials. Dose reductions to manage adverse events (AEs) were allowed; prior analysis showed no impact on progression-free survival with RIB dose reduction (Beck, et al. SABCS 2018). Here we present data on RIB dose reductions and evaluate the impact on OS in ML-3 and -7. ML-3 randomized pts 2:1 to RIB or PBO (both + fulvestrant). ML-7 randomized pts 1:1 to RIB or PBO (both + ET); only pts treated with a nonsteroidal aromatase inhibitor were included in this analysis. Separate time-varying Cox regression models considering dose modifications over time were used to assess impact of dose reduction (from 600 mg) or relative dose intensity (RDI; accounts for reduction or interruption) on OS. Pooled ML-3/-7 data were analyzed to explore the relationship between pharmacokinetic RIB exposure (Ctrough) and OS. Pts by dose reduction and RDI are outlined in the table. In ML-3, HR for OS was 0.88 (95% CI, 0.64-1.21) in pts with ≥ 1 vs. 0 dose reduction, 0.98 (95% CI, 0.68-1.42) for low vs. high RDI, and 0.87 (95% CI, 0.60-1.27) for medium vs. high RDI. In ML-7, HR for OS was 0.79 (95% CI, 0.46-1.36) in pts with ≥ 1 vs. 0 dose reduction, 0.82 (95% CI, 0.44-1.52) for low vs. high RDI, and 0.88 (95% CI, 0.48-1.61) for medium vs. high RDI. Exposure-efficacy analysis suggested no clear impact of RIB exposure on OS relating to dose reductions of 400 and 200 mg.TableDose reductionRDI (%)≥ 1NoneLow1st tertileMedium2nd tertileHigh3rd tertileML-3, n (%)197 (41)286 (59)[<77.01]160 (33)[77.01-97.66]163 (34)[>97.66]160 (33)ML-7, n (%)101 (41)145 (59)[<73.43]81 (33)[73.43-97.70]84 (34)[>97.70]81 (33) Open table in a new tab RIB dose reduction does not compromise OS benefit as evidenced by the lack of relationship observed between OS and RIB dose reduction, RDI, or drug exposure. This suggests that pts starting on RIB at 600 mg who require a dose modification for AE management or other reasons do not attenuate the survival benefit.