Abstract P1-18-11: Analysis of first-line (1L) patients (pts) with de novo disease vs late relapse and all pts with vs without prior chemotherapy (CT) in the MONALEESA-3 (ML-3) trial
Authors: De Laurentiis Michelino , Lambertini Matteo , Chia Stephen , Rugo Hope S , Petrakova Katarina , Villanueva Cristian , Hurvitz Sara , Beck J. Thaddeus , Lteif Agnes , Haftchenary Sina , Deore Uday , Wu Jiwen , El-Saghir Nagi 
Published: March 2022

Background: The phase 3 ML-3 trial demonstrated significant OS benefit for ribociclib (RIB) + fulvestrant (FUL) over placebo (PBO) + FUL as first- or second- line therapy in postmenopausal pts with HR+/HER2- advanced breast cancer (ABC). Prior treatment ([neo]adjuvant or advanced setting) may impact subsequent therapy outcomes, including OS; therefore, understanding the potential effect of prior treatment is of high clinical interest. Here, we present PFS and OS data from 2 subgroup analyses in ML-3: 1L pts with de novo disease vs late relapse and all pts with vs without prior CT. Methods: ML-3 (NCT02422615) enrolled postmenopausal pts who were randomized 2:1 to receive RIB + FUL or PBO + FUL. Pts with prior ET ([neo]adjuvant or ≤1 prior ET for ABC) and no CT for ABC were included. Pts with de novo disease were defined as initially diagnosed as ABC with no prior treatment for ABC. Pts with late relapse were defined as those who relapsed &gt;12 months from completion of (neo)adjuvant ET with no prior treatment for ABC. Since prior CT for ABC was not allowed in ML-3, the prior CT analysis compares pts with prior (neo)adjuvant CT vs those without prior (neo)adjuvant CT. Results: The data cutoff was October 30, 2020. Within the 1L population, in the de novo vs late relapse analysis, 132 pts (RIB: n = 91; PBO: n = 41) had de novo disease, and 153 had late relapse (RIB: n = 98; PBO: n = 55). Baseline characteristics were generally balanced between the de novo and late relapse groups, with some notable exceptions: a higher proportion of pts with de novo disease were aged &lt;65 years (52.3% vs 41.8%) and a lower proportion had visceral disease (53.0% vs 63.4%). In the late relapse group, 70.6% had prior (neo)adjuvant CT. De novo disease or late relapse did not appear to be prognostic as both PFS and OS were generally comparable between those 2 groups among pts treated with RIB or those treated with PBO (Table). Treatment with RIB + FUL demonstrated consistent PFS and OS benefits over PBO + FUL in both pts with de novo disease and those with late relapse. In the prior CT analysis, 391 pts (RIB: n = 265; PBO: n = 126) had prior CT (41.4% in 1L and 55.5% in 2L/early relapse [3.1% data missing]) and 334 (RIB: n = 219; PBO: n = 115) had no prior CT (60.8% in 1L, 38.9% in 2L/early relapse [0.3% data missing]). Baseline characteristics were generally balanced between pts with and without prior CT, with some exceptions: a higher proportion of pts with prior CT were aged &lt;65 years (62.1% vs 42.8%) and had prior ET in any setting (86.4% vs 53.0%). Pts without prior CT had longer median PFS and OS compared with those who had prior CT in both the RIB and PBO arms (OS without vs with prior CT treated with RIB: HR, 0.68 [95% CI, 0.52-0.89]; PBO: HR, 0.72 [95% CI, 0.52-1.00]). Treatment with RIB + FUL demonstrated consistent PFS and OS benefits over PBO + FUL in both pts with prior CT and those without (OS for RIB vs PBO with prior CT: HR, 0.76 [95% CI, 0.58-1.01]; without prior CT: HR, 0.70 [95% CI, 0.50-0.97]). Conclusions: This exploratory analysis demonstrated that metastatic presentation (de novo vs late relapse) was not prognostic for disease outcomes; however, prior CT exposure, even in (neo)adjuvant, was associated with poorer PFS and OS. The addition of RIB showed consistent PFS and OS benefit across all subgroups in this analysis. Particularly, the addition of RIB resulted in a consistent and clinically meaningful PFS and OS benefit with a decrease in relative risk of death by 24% in pts with prior exposure to CT.

RIB + FULPBO + FULHR (RIB vs PBO)De novo/late relapseMedian PFS (95% CI), monthsDe novo35.6. (27.1-42.0)22.1. (14.6-33.1)0.55. (0.35-0.86)Late relapse35.8. (20.0-44.4)22.0. (16.5-27.7)0.60. (0.40-0.89)HR (de novo vs late elapse)0.93. (0.64-1.36)0.996. (0.63-1.57)Median OS (95% CI), monthsDe novo59.9. (52.7-NE)52.9. (39.6-NE)0.67. (0.38-1.19)Late relapseNE. (54.9-NE)52.3. (40.4-NE)0.69. (0.42-1.13)HR (de novo vs late relapse)0.899. (0.552-1.465)0.91. (0.51-1.62)Prior (neo)adjuvant CTMedian PFS (95% CI), monthsWithout prior CT28.3. (23.3-35.6)17.5. (13.6-21.9)0.60. (0.46-0.78)With prior CTa17.9. (14.3-19.9)10.8. (7.2-12.3)0.61. (0.48-0.78)HR (without vs with prior CT)0.76. (0.60-0.94)0.72. (0.55-0.95)Median OS (95% CI), monthsWithout prior CTNE (54.9-NE)44.9 (38.5-58.1)0.70. (0.50-0.97)With prior CTa43.0 (39.1-51.2)40.1 (30.3-48.6)0.76. (0.58-1.01)HR (without vs with prior CT)0.68 (0.52-0.89)0.72 (0.52-1.00)NE, not estimable a Includes 4 patients who received prior CT for ABC (protocol violation).

Citation Format: Michelino De Laurentiis, Matteo Lambertini, Stephen Chia, Hope S Rugo, Katarina Petrakova, Cristian Villanueva, Sara Hurvitz, J. Thaddeus Beck, Agnes Lteif, Sina Haftchenary, Uday Deore, Jiwen Wu, Nagi El-Saghir. Analysis of first-line (1L) patients (pts) with de novo disease vs late relapse and all pts with vs without prior chemotherapy (CT) in the MONALEESA-3 (ML-3) trial [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P1-18-11.