Background: In the PALOMA-2 trial, PAL + letrozole (LET) significantly prolonged progression-free survival (PFS) vs placebo (PBO) + LET in pts with ER+/HER2– ABC. This post hoc analysis assessed efficacy and safety of PAL + LET in pts from PALOMA-2 with baseline preexisting conditions grouped by Medical Dictionary for Regulatory Activities (MedDRA) System Organ Class (SOC). Methods: Postmenopausal pts with ER+/HER2– ABC received PAL (125 mg/d, 3/1 schedule) + LET (2.5 mg/d, continuous) or PBO + LET. Pts were grouped by the following MedDRA SOC preexisting conditions: Gastrointestinal, Musculoskeletal, Metabolism, and Vascular/Cardiac. Baseline characteristics, PFS, and safety were assessed. Results: At baseline, 41.4% of pts had preexisting gastrointestinal disorders, 58.6% musculoskeletal disorders, 38.9% metabolism disorders, and 57.4% vascular/cardiac disorders. Baseline characteristics were similar between treatment arms within each subgroup and also between subgroups. Within each subgroup, ≥40% of pts also had ≥1 of the other coexisting conditions. Median PFS (mPFS) was significantly longer with PAL + LET vs PBO + LET regardless of preexisting condition (Table). In general, adverse events (AEs) were more frequent with PAL + LET in all subgroups; neutropenia was most common. Within each treatment arm, AEs and dose modifications due to AEs were similar regardless of preexisting condition. Conclusion: PAL + LET showed prolonged PFS and a consistent safety profile regardless of baseline preexisting condition in pts with ER+/HER2– ABC. Clinical trial identification: Pfizer Inc (NCT01740427)

Table

Preexisting ConditionPAL + LETPBO + LETPAL + LET vs PBO + LET
nmPFS (95% CI)nmPFS (95% CI)HR (95% CI)P Value
Gastrointestinal 176 27.6 (17.5–33.1) 100 13.6 (11.0–18.5) 0.57 (0.42–0.78) <0.001 
Musculoskeletal 252 27.6 (21.4–33.1) 138 16.3 (11.2–19.1) 0.53 (0.41–0.69) <0.001 
Metabolism 186 27.6 (19.3–30.6) 73 13.8 (8.3–27.4) 0.62 (0.44–0.87) 0.003 
Vascular/Cardiac 254 30.4 (25.1–36.2) 128 14.5 (11.0–18.5) 0.51 (0.39–0.66) <0.001 
Preexisting ConditionPAL + LETPBO + LETPAL + LET vs PBO + LET
nmPFS (95% CI)nmPFS (95% CI)HR (95% CI)P Value
Gastrointestinal 176 27.6 (17.5–33.1) 100 13.6 (11.0–18.5) 0.57 (0.42–0.78) <0.001 
Musculoskeletal 252 27.6 (21.4–33.1) 138 16.3 (11.2–19.1) 0.53 (0.41–0.69) <0.001 
Metabolism 186 27.6 (19.3–30.6) 73 13.8 (8.3–27.4) 0.62 (0.44–0.87) 0.003 
Vascular/Cardiac 254 30.4 (25.1–36.2) 128 14.5 (11.0–18.5) 0.51 (0.39–0.66) <0.001 

Citation Format: Karen Gelmon, Janice M Walshe, Reshma Mahtani, Anil A Joy, Meghan Karuturi, Patrick Neven, Dongrui Ray Lu, Sindy Kim, Patrick Schnell, Eustratios Bananis, Lee Schwartzberg. Efficacy and safety of palbociclib (PAL) in patients (pts) with estrogen receptor-positive (ER+)/human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer (ABC) with preexisting conditions: A post hoc analysis of PALOMA-2 [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS10-14.