Background: BOLERO 2 trial showed improved progression free survival (PFS) with everolimus (EV) + exemestane combination over exemestane alone in hormone receptor positive, HER2 non-amplified metastatic breast cancer patients (HR+ HER2- MBC) who progressed on an aromatase inhibitor (AI). Recent studies have established CDK 4/6 inhibitors (CDKI) as front line therapy in HR+ HER2- MBC. There are no clinical outcome data of HR+ HER2- MBC on EV after they progress on CDKI. Objective of our study is to analyze clinical outcomes of HR+ HER2- MBC on EV after progression on palbociclib (PA) & compare them with BOLERO 2 results. Methods: This is a retrospective, two-institute review of HR+ HER2- MBC from Jan 2015-July 2017 treated with EV after progression on PA. Women who received EV or PA < 4 weeks were excluded. PFS was defined as the time from the initiation of EV to the date of progression as determined by treating physician based on radiological, biochemical and/or clinical criteria. Response rates were determined based on available radiological data. Results: 26 women with median age 61 (33-70) were identified. 76% had prior sensitivity to endocrine therapy, 69% had adjuvant chemo/hormonal therapy, 54% had visceral disease, 23% had 3 or more metastatic sites, 100% had ECOG performance status 0 or 1, 92% had prior AI, 65% had received chemotherapy, 35% had received chemotherapy for metastatic disease, 81% had 3 or more lines of prior therapy. Kaplan Meier estimate showed median PFS (95% CI) of 4.4 months (3.3-6.1) and median overall survival (OS) of 18.7 months (9.0- not reached). Median PFS and OS of EV cohort of BOLERO 2 (EV BOL) were 6.9 months (6.4-8.1) and 31.0 months (28.0-34.6). Fisher’s exact test comparing current study cohort vs. EV BOL showed significant difference in objective response (complete + partial responses) of 6/26 (23%) vs. 46/485 (9.5%), p = 0.04. Conclusions: EV showed shorter PFS and OS but significantly higher objective response in HR+ HER2- MBC who have progressed on PA compared to EV BOL. This small study, for the first time, suggests that EV has evidence of clinical benefit after progression on PA in HR+ HER2- MBC. Larger studies are needed to confirm the results.