455P Post progression treatments after endocrine therapy (ET) plus palbociclib in patients with HR+/HER2- metastatic breast cancer (MBC): A prospective, real-world study

The association of ET and CDK 4/6 inhibitors (CDK 4/6i) is the gold standard of treatment in women with HR+/HER2- MBC. The optimal therapeutic strategy after CDK 4/6i progression is still a matter of debate. The present study aimed to evaluate the benefit of the different treatments adopted in a real-world context. In this prospective study we included women with HR+/HER2- MBC progressing to ET plus palbociclib (P). Either ET or chemotherapy (CT) were prescribed taking into account:1) site and burden of disease (visceral/plurimetastatic vs bone only/oligometastatic); 2) median PFS1 (<4 months vs ≥4 months); 3) tolerability profile; 4) patient’s preferences. Primary objective was median progression-free survival 2 (PFS2). Secondary aims: analysis of the determinants of physician’s choice, clinical benefit rate (CBR), impact of neutrophil-to lymphocyte ratio (NLR), monocyte-to lymphocyte ratio (MLR), platelet-to lymphocyte ratio (PLR) and body mass index (BMI) on PFS2. From May 2017 to October 2021, 78 pre- and postmenopausal patients were enrolled and 56 were evaluable for the final analysis: 18 had received ET plus P as 1st line, 38 in ≥2nd line; 22 patients were excluded because they were still on therapy at the time of the last follow-up. At progression 15 patients (26.7%) received ET (everolimus+exemestane 8, fulvestrant 7) and 41 (73.2%) were treated with CT (eribulin, capecitabine, nab-paclitaxel, vinorelbine). In the whole population mPFS1 was 17.5 months; mPFS2 was 5 months in the overall cohort (95% CI = 4-48 months) with a significant difference between ET and CT (10 months vs 5 months, p=0.035); CBR was 50% and 55.2%, in ET and CT, respectively. At multivariate analysis CT prescription was associated to a higher visceral burden and a shorter mPFS1. Elevated NLR and PLR were correlated with worse PFS2 in both treatment groups, while no impact of MLR and BMI was observed. In this real life experience, treatments beyond ET plus P failure provided limited but comparable clinical benefit. The physician’s choice was clearly driven by visceral burden of disease; the inflammatory status seems to have a detrimental effect on PFS2.