Abstract P4-22-16: First-line ribociclib + letrozole in patients with HR+, HER2– advanced breast cancer (ABC) presenting with visceral metastases or bone-only disease: A subgroup analysis of the MONALEESA-2 trial
Authors: Burris HA , Chan A , Campone M , Blackwell KL , Winer EP , Janni W , Verma S , Burdaeva O , Alba E , Favret AM , Mondal S , Miller M , Germa C , Hirawat S , Yap YS 
Published: March 2017

Abstract
Background: Patients with ABC who present with visceral metastases have a worse outcome than patients with non-visceral disease, while patients with bone-only disease tend to have a better prognosis. Ribociclib (LEE011) is an oral, selective inhibitor of cyclin-dependent kinase (CDK) 4/6. In a Phase 3, placebo-controlled, randomized trial (MONALEESA-2; NCT01958021), first-line ribociclib (R) + letrozole (L) significantly prolonged progression-free survival (PFS) vs placebo (P) + L in patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2–) ABC, with a hazard ratio of 0.556 (95% confidence interval [CI]: 0.429–0.720; p=0.00000329) at the interim analysis cut-off date (Jan 29, 2016). Here, we present subgroup analyses in patients with visceral metastases, and those with bone-only disease.
Methods: Postmenopausal women with HR+, HER2– ABC were randomized 1:1 to receive R (600 mg/day; 3-weeks-on/1-week-off) + L (2.5 mg/day; continuous) or P+L, stratified by the presence of liver and/or lung metastases. No prior CDK4/6 inhibitors or systemic therapy for ABC were allowed. Eligible patients had Eastern Cooperative Oncology Group performance status ≤1, baseline alanine/aspartate aminotransferase levels &lt;5× upper limit of normal (ULN) or &lt;2.5× ULN for patients with or without liver metastases, respectively, and ≥1 predominantly lytic bone lesion at baseline for patients with bone-only disease. Locally assessed PFS was analyzed for all patients (primary endpoint), and for predefined patient subgroups.
Results: Overall, 668 patients were randomized; 393 had visceral metastases and 147 had bone-only disease.
Visceral metastasesBone-only disease n=393n=147 R+LP+LR+LP+L n=197n=196n=69n=78Median age, years (range)63 (23–91)63 (29–88)65 (37–85)63 (37–84)De novo metastatic disease, n (%)53 (27)55 (28)28 (41)24 (31)Non-de novo disease-free interval, n (%)≤24 months12 (6)15 (8)5 (7)6 (8)&gt;24 months132 (67)126 (64)36 (52)48 (62)Discontinued treatment, n (%)83 (42)111 (57)29 (42)40 (51)Reason for discontinuation, n (%)Disease progression56 (28)93 (47)17 (25)31 (40)Patient/physician decision10 (5)15 (8)7 (10)6 (8)Adverse events16 (8)3 (2)4 (6)2 (3)Protocol deviation001 (1)1 (1)Death1 (&lt;1)000
In patients with visceral metastases: Median PFS was not reached in the R+L arm (95% CI: 19.3–not estimable [NE]) vs 13.0 months (95% CI: 12.6 –16.5) in the P+L arm, with hazard ratio 0.535 (95% CI: 0.385–0.742). Median duration of exposure was 12.0 and 13.0 months (R and L, respectively) in the R+L arm, and 12.1 and 12.2 months (P and L, respectively) in the P+L arm.
In patients with bone-only disease: Median PFS was not reached in the R+L arm (95% CI: NE–NE) vs 15.3 months (95% CI: 13.8–NE) in the P+L arm, with hazard ratio 0.690 (95% CI: 0.381–1.249). Median duration of exposure was 12.1 and 12.6 months (R and L, respectively) in the R+L arm, and 12.7 and 12.9 months (P and L, respectively) in the P+L arm.
Conclusions: First-line R+L was well tolerated and significantly prolonged PFS vs P+L in postmenopausal women with HR+, HER2– ABC, both in patients with visceral metastases and those with bone-only disease.
Keywords: Advanced breast cancer; CDK4/6 inhibitor; Letrozole; Ribociclib
Citation Format: Burris HA, Chan A, Campone M, Blackwell KL, Winer EP, Janni W, Verma S, Burdaeva O, Alba E, Favret AM, Mondal S, Miller M, Germa C, Hirawat S, Yap YS. First-line ribociclib + letrozole in patients with HR+, HER2– advanced breast cancer (ABC) presenting with visceral metastases or bone-only disease: A subgroup analysis of the MONALEESA-2 trial [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P4-22-16.