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
Authors: 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 
Published: February 2018

Abstract
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&lt;.001) after a median 23 mo follow-up (FU) (Finn et al. 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&lt;.0001; Table).
TABLE. mPFS overall and by relevant subgroupsP+LPBO+LP+L vs PBO+LmPFS, mo (95% CI)mPFS, mo (95% CI)HR (95% CI)P* Overall27.6 (22.4–30.3)14.5 (12.3–17.1)0.56 (0.46–0.69)&lt;.0001 Measurable disease23.7 (19.3–27.6)14.5 (12.3–18.5)0.63 (0.50–0.79)&lt;.0001 Nonmeasurable disease36.2 (27.6?NE)16.5 (8.3–19.6)0.39 (0.25–0.60)&lt;.0001 Visceral19.3 (16.4–24.2)12.3 (8.4–16.4)0.62 (0.47–0.81)&lt;.0005 Nonvisceral35.9 (27.7–NE)17.0 (13.8–24.8)0.50 (0.37–0.67)&lt;.0001 Bone only†36.2 (27.6–NE)11.2 (8.2–22.0)0.41 (0.26–0.63)&lt;.0001 Not bone only24.2 (19.4–27.7)14.5 (12.9–18.5)0.62 (0.50–0.78)&lt;.0001 De novo metastatic27.9 (22.1–33.4)22.0 (13.9–27.4)0.61 (0.44–0.85)&lt;.005 Prior ET24.2 (18.8–27.6)11.2 (8.4–14.5)0.54 (0.42–0.71)&lt;.0001 No prior ET30.3 (24.5–35.7)21.9 (15.9–27.4)0.59 (0.43–0.80)&lt;.0005 Nonvisceral36.2 (27.9–NE)27.6 (19.1–35.6)0.59 (0.38–0.92)&lt;.01 Visceral23.7 (16.8–30.3)13.9 (10.2–22.2)0.55 (0.36–0.85)&lt;.005 Disease sites130.4 (24.8–NE)16.5 (11.0–22.1)0.52 (0.36–0.75)&lt;.0005228.1 (19.4–NE)16.3 (11.0–27.4)0.57 (0.37–0.89)&lt;.01323.7 (19.2–27.6)13.8 (8.8–17.0)0.61 (0.46–0.82)&lt;.0005NE=not estimable. *Not adjusted for multiple analyses; 1-sided P values. †Per tumor site.
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&lt;.01). Importantly, median time from randomization to start of 2nd subsequent systemic anticancer therapy was 39 vs 29 mo for P+L vs PBO+L (HR=0.72, P&lt;.005). There were no new safety signals w/ longer FU.
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 &gt;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.