Abstract GS2-01: Overall survival subgroup analysis by metastatic site from the phase 3 MONALEESA-2 study of first-line ribociclib + letrozole in postmenopausal patients with advanced HR+/HER2− breast cancer
Authors: O'Shaughnessy Joyce , Stemmer Salomon M , Burris Howard A , Yap Yoon-Sim , Sonke Gabe , Hart Lowell , Campone Mario , Petrakova Katarina , Winer Eric P , Janni Wolfgang , Conte Pierfranco , Cameron David A , André Fabrice , Arteaga Carlos , Zarate Juan Pablo , Chakravartty Arunava , Taran Tetiana , Gac Fabienne Le , Serra Paolo , Hortobagyi Gabriel N 
Published: March 2022

Abstract
Background: MONALEESA-2 (ML-2) recently reported a statistically significant overall survival (OS) benefit with first-line ribociclib (RIB) + letrozole (LET) over placebo (PBO) + LET in postmenopausal patients with HR+/HER2- advanced breast cancer (ABC) (median, 63.9 vs 51.4 months; hazard ratio, 0.76; 95% CI, 0.63-0.93; P = .004). Understanding OS outcomes in clinically relevant subgroups of patients is important for improving personalized care and prognosis. Here, we report the results of a prespecified exploratory OS analysis in select patient subgroups by baseline location and number of metastatic sites.. Methods: Postmenopausal patients with HR+/HER2− ABC were randomized 1:1 to receive first-line RIB or PBO with LET. Prespecified exploratory OS analyses were performed for subgroups of special interest by baseline location (bone only [yes or no], liver involvement [yes or no], liver or lung involvement [yes or no]) and number of metastatic sites (&lt; 3 or ≥ 3). The data are hypothesis generating since this analysis was exploratory and not powered for statistical significance.. Results: A total of 668 patients were included in the analysis. A consistent improvement in OS was observed with RIB + LET vs PBO + LET in all subgroups regardless of baseline metastatic site (Table). RIB + LET demonstrated an OS benefit over PBO + LET in clinically relevant subgroups by baseline location and number of metastatic sites, including subgroups of patients with liver metastases, liver or lung metastases, and ≥ 3 metastatic sites, who generally have a worse prognosis.. Conclusion: Consistent with the intent-to-treat population of ML-2, the results of this prespecified exploratory analysis demonstrated an OS benefit with RIB + LET independent of the site and number of metastatic lesions.
TableTreatment Arm (n)HR (95% CI)Bone-only metastasisYesRIB + LET (69)0.78 (0.50-1.21)PBO + LET (79)NoRIB + LET (265)0.77(0.61-0.96)PBO + LET (255)Liver involvementYesRIB + LET (59)0.81 (0.54-1.24)PBO + LET (72)NoRIB + LET (275)0.77 (0.62-0.97)PBO + LET (262)Liver or lung involvementYesRIB + LET (182)0.81(0.62-1.05)PBO + LET (190)NoRIB + LET (152)0.71 (0.53-0.96)PBO + LET (144)No. of metastatic sites&lt; 3RIB + LET (220)0.78(0.61-1.00)PBO + LET (222)≥ 3RIB + LET (114)0.71(0.51-0.98)PBO + LET (112)
Citation Format: Joyce O'Shaughnessy, Salomon M Stemmer, Howard A Burris, Yoon-Sim Yap, Gabe Sonke, Lowell Hart, Mario Campone, Katarina Petrakova, Eric P Winer, Wolfgang Janni, Pierfranco Conte, David A Cameron, Fabrice André, Carlos Arteaga, Juan Pablo Zarate, Arunava Chakravartty, Tetiana Taran, Fabienne Le Gac, Paolo Serra, Gabriel N Hortobagyi. Overall survival subgroup analysis by metastatic site from the phase 3 MONALEESA-2 study of first-line ribociclib + letrozole in postmenopausal patients with advanced HR+/HER2− breast cancer [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 GS2-01.