Abstract P1-18-13: Efficacy and safety of palbociclib plus endocrine therapy in Black and Hispanic patients with hormone receptor positive/human epidermal growth factor receptor 2-negative advanced breast cancer (HR+/HER2- ABC) participating in the PALOMA trials
Authors: Isaacs Claudine , Mahtani Reshma , Lynce Filipa , Sleckman Bethany , Castrellon Aurelio , Kalmadi Sujith , Theall Kathy Puyana , Huang Xin , Bananis Eustratios , Rugo Hope S. 
Published: March 2022

Background: The PALOMA clinical trials have shown that palbociclib (PAL) plus endocrine therapy (ET) is a safe and effective treatment for HR+/HER2- ABC. However, Black and Hispanic patients are underrepresented in clinical trials and the efficacy and safety of CDK4/6 inhibitors in these populations have not been reported. This post hoc analysis describes the efficacy and safety of PAL + ET in Black and Hispanic patients with HR+/HER2- ABC enrolled in the PALOMA trials. Methods: Postmenopausal patients were treated with letrozole (LET) + PAL on a 125 mg/d, 3/1 weekly schedule or LET alone (PALOMA-1) or LET + placebo (PBO; PALOMA-2) in the 1st line setting. In PALOMA-3, pre/postmenopausal patients were treated with fulvestrant (FUL) + PAL or PBO, with or without a luteinizing hormone releasing hormone agonist, in the ≥1st-line setting. Median progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method. Treatment-emergent adverse events (AEs) were evaluated according to the National Cancer Institute Common Terminology Criteria for AEs. Results: In PALOMA-2, Black and Hispanic patients comprised 9.8% of the population and had a median age of 58 yrs (PAL + LET arm; n=47) and 54 yrs (PBO + LET arm; n=18). Patients treated with PAL + LET had more visceral disease (62% vs 50%), lung involvement (51% vs 22%), de novo disease (45% vs 22%) and less prior systemics (55% vs 78%) compared to patients treated with PBO + LET. In PALOMA-3, Black and Hispanic patients comprised 9.2% of the population and had a median age of 57 yrs in both the PAL + FUL (n=29) and PBO + FUL (n=19) arms, with baseline characteristics being generally similar between the two arms. PAL+ ET prolonged median PFS in PALOMA-2 and -3 and prolonged median OS in PALOMA-3 compared to PBO + ET (Table 1). In pooled analyses of these patients from PALOMA 1-3 (n=120), the most common grade 3/4 AEs with PAL + ET were neutropenia (57.7%), leukopenia (24.4%), and anemia (3.8%), similar to the rates in the pooled PALOMA 1−3 overall as-treated population (Table 2). None of these grade 3/4 AEs were reported with PBO + ET in the Black/Hispanic subgroup (Table 2). Febrile neutropenia or pulmonary embolism were not reported in either arm. The rate of dose reduction due to AEs was 37.2% with PAL + ET, similar to the rates of dose reduction across the populations in the PALOMA trials (39.4%−42.2%). Conclusion: In Black/Hispanic pts with HR+/HER2- ABC enrolled in the PALOMA-2 and -3 trials, PAL + ET, in the first or greater lines, was an efficacious treatment option with no increased toxicity rates. These findings support the continued use of PAL + ET as a standard of care in these patients. Considering the substantial burden of breast cancer in Black and Hispanic patients, their relatively small representation in the PALOMA trial program highlights the need to increase diversity in clinical trials. Clinical trial identification: Pfizer (NCT00721409, NCT01740427, NCT01942135)

Table 1.Median PFS and OS in the ITT population and Black and Hispanic patients from PALOMA-2 and -3Median (95% CI), moHazard Ratioa (95% CI)PAL + ETPBO + ETPAL + ET vs PBO + ETPFSPALOMA-2ITT [n=666]27.6 (22.4-30.3)14.5 (12.3-17.1)0.56 (0.46-0.69)Black and Hispanic [n=65]27.4 (13.8-NE)13.8 (8.1-30.7)0.61 (0.31-1.2)PALOMA-3ITT [n=521]11.2 (9.5-12.9)4.6 (3.5-5.6)0.50 (0.40-0.62)Black and Hispanic [n=48]11.1 (4.5-12.0)1.9 (1.8-5.7)0.56 (0.28-1.14)OSPALOMA-3ITT [n=521]34.8 (28.8-39.9)28.0 (23.5-33.8)0.79 (0.64-0.97)Black and Hispanic [n=48]35.6 (24.0-58.2)21.0 (14.3-35.4)0.48 (0.23-0.97)ET=endocrine therapy; ITT=intent to treat; NE=not estimable; OS=overall survival; PAL=palbociclib; PBO=placebo; PFS=progression free survival.aEstimated from an unstratified Cox proportional hazards model.

Table 2.Grade 3/4 treatment emergent adverse events in the overall as-treated population and Black and Hispanic subgroup pooled from the PALOMA trialsPooled PALOMAPooled Black/HispanicAE, No. (%)PAL + ET (n=872)ETa (n=471)PAL + ET (n=78)PBO + ET (n=42)Any AE662 (75.9)110 (23.4)53 (67.9)12 (28.6)Neutropenia570 (65.4)5 (1.1)45 (57.7)0Leukopenia233 (26.7)2 (0.4)19 (24.4)0Anemia40 (4.6)9 (1.9)3 (3.8%)0Thrombocytopenia17 (1.9)1 (0.2)1 (1.3%)1 (2.4)Infections45 (5.2)12 (2.5)1 (1.3%)1 (2.4)AE=adverse event; ET=endocrine therapy; PAL=palbociclib; PBO=placebo.aEndocrine therapy with placebo (PALOMA-2 and 3) and without placebo (PALOMA-1).

Citation Format: Claudine Isaacs, Reshma Mahtani, Filipa Lynce, Bethany Sleckman, Aurelio Castrellon, Sujith Kalmadi, Kathy Puyana Theall, Xin Huang, Eustratios Bananis, Hope S. Rugo. Efficacy and safety of palbociclib plus endocrine therapy in Black and Hispanic patients with hormone receptor positive/human epidermal growth factor receptor 2-negative advanced breast cancer (HR+/HER2- ABC) participating in the PALOMA trials [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 P1-18-13.