Abstract P5-21-03: Palbociclib (PAL) + letrozole (LET) as first-line therapy in estrogen receptor–positive (ER+)/human epidermal growth factor receptor 2–negative (HER2−) advanced breast cancer (ABC): Efficacy and safety updates with longer follow-up across patient subgroups

BACKGROUND: Endocrine therapy (ET) has been the primary first-line (1L) therapy for ER+ ABC. In the PALOMA-2 study (NCT01740427), PAL (P)+LET (L) significantly prolonged progression-free survival (PFS; HR=0.58, P NEJM 2016). Here we report more mature PFS overall and in subgroups, with (w/) longer FU. The study is ongoing for overall survival FU. METHODS: Postmenopausal pts w/ ER+/HER2- ABC and no prior systemic therapy in the ABC setting were randomized 2:1 to P (125 mg/d) + L (2.5 mg QD) or placebo (PBO) + L. Key endpoints: investigator-assessed PFS and safety. Median PFS (mPFS) was estimated (intent-to-treat population). RESULTS: 666 pts (444, P+L; 222, PBO+L) were enrolled. Arms were well balanced: visceral (48%)/nonvisceral (52%) disease and prior ET (56%)/no prior ET (44%). After a median FU of 38 mo w/ P+L and 37 mo w/ PBO+L, mPFS was 27.6 and 14.5 mo, respectively, in the overall population (HR=0.56, P Table ). All subgroups benefited from addition of P to L. Notably, pts w/ low disease burden (bone only, nonvisceral disease, few disease sites) derived significant PFS benefit, including those w/ both nonvisceral disease and no prior ET (mPFS, 36.2 vs 27.6 mo; HR=0.59, P P CONCLUSIONS: This is the longest FU of a phase 3 study of a cyclin-dependent kinase 4/6 inhibitor for ABC. P+L continues to consistently improve PFS vs PBO+L across all subgroups while toxicity remains manageable; notably P+L delays time to starting 2nd subsequent anticancer therapies by 10 mo. Pts w/ low disease burden or sensitivity to ET alone had PFS >3 y (significant vs PBO+L), demonstrating the clinical benefit of P+ET. These data confirm P+L should be a 1L therapy option for pts w/ HR+/HER2- ABC. Funding: Pfizer Citation Format: Rugo HS, Finn RS, Dieras V, Ettl J, Lipatov O, Joy A, Harbeck N, Castrellon A, Lu DR, Mori A, Gauthier ER, Huang C, Gelmon KA, Slamon DJ. Palbociclib (PAL) + letrozole (LET) as first-line therapy in estrogen receptor–positive (ER+)/human epidermal growth factor receptor 2–negative (HER2−) advanced breast cancer (ABC): Efficacy and safety updates with longer follow-up across patient subgroups [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P5-21-03.